The Tissue Nonspecific Alkaline Phosphatase
Gene Mutations Database

(ALPL ; NM_000478.5)

 

Welcome to the ALPL gene mutations database. This site has been compiled to provide up-to-date information about genetic variation of the ALPL gene responsible for hypophosphatasia.

The database has been initiated by the SESEP Laboratory (now integrated in Versailles Hospital as the Unit of Constitutional Genetics) and the Unit of Cell and Genetics Pathology (EA2493) of the University of Versailles-Saint Quentin en Yvelines, France.



The database

Editor : Etienne MORNET Ph.D.
Last update : January 28, 2020
Total number of mutations described :
4
09



Hypophosphatasia (MIM 146300, 241500, 241510)

Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by defective bone and teeth mineralization and deficiency of serum and bone alkaline phosphatase activity. The clinical presentation is a continuum ranging from a prenatal lethal form with no skeletal mineralization to a mild form with late adult onset presenting with nonpathognomonic symptoms. A classification according to the age of diagnosis mostly based on the age of diagnosis is used: perinatal lethal (ORPHA 247623), prenatal benign ( ORPHA247638), infantile (ORPHA 247651), childhood ORPHA 247667), adult (ORPHA 247676), and odontoHPP (ORPHA 247685).The prevalence of severe forms is low (estimated at 1/300,000 in Europe, 1/100,000 in North America), whereas less severe forms are more frequently observed (estimated at 1/6000 in Europe). The disease is caused by loss-of-function mutations in the ALPL gene encoding the Tissue Nonspecific Alkaline Phosphatase (TNSALP), a central regulator of mineralization (Harmey et al. 2004). Severe forms (perinatal and infantile) are recessively inherited, whereas moderate forms are either recessively or dominantly inherited, and the more severe the disease is, the more often it is subject to recessive inheritance (Fauvert et al. 2009). The diagnosis is based on a constantly low alkaline phosphatase (AP) activity in serum and genetic testing that identifies ALPL mutations. More than 400 mutations have been identified and are responsible for the extraordinary clinical heterogeneity. A clear but imperfect genotype-phenotype correlation has been observed, suggesting that other genetic or environmental factors modulate the phenotype. Enzyme replacement therapy is now available for HPP (Whyte et al. 2012), and other approaches, such as gene therapy, are currently being investigated (Ikeue et al. 2018). The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early loss of tooth without bone symptoms (Whyte 1994). The transmission of severe forms is autosomal recessive while milder forms may be transmitted as dominant or recessive autosomal traits. The disease is due to mutations in the alkaline phosphatase liver-type (ALPL) gene, also named the TNSALP gene. See more informations in Orphanet.

The ALPL gene (ID:249; MIM 171760), localized on chromosome 1p36-34 (Greenberg et al. 1990), consists of 12 exons distributed over 70 kb (Weiss et al. 1988) and is subject to very strong allelic heterogeneity. To date, at least 409 distinct mutations are known.

Table of mutations

Exon 1 | Exon 2 | Exon 3 | Exon 4 | Exon 5 | Exon 6 | Exon 7 | Exon 8 | Exon 9 | Exon 10 | Exon 11 | Exon 12 | Large deletions/duplications | Polymorphisms (not updated)

Exon Base change
Amino acid change

(standardized nomenclature)


Pathogenicity

Amino acid change

(Non standardized nomenclature)


Reference
Clinical form of the patient Genotype of the patient


Residual activity

Dominant negative effect
Conservation
%
WT
reference
% 50/50
reference
1 c.-195C>T   P   Taillandier et al. 2000 perinatal c.[-195C>T];[602G>A]         na
                         
2 c.3G>A p.Met1Ile LP Met-17Ile Mentrup et al. 2011 adult c.[3G>A];[?] 1.0 Mentrup et al. 2011 59.0 Mentrup et al. 2011 ++
2 c.17T>A p.Leu6* P Leu-12Ter Taillandier et al. 2000 childhood c.[17T>A];[?]         na
2 c.18delA p.Val7Tyrfs P Val-11Tyrfs Cui et al. 2012 infantile c.[18delA];[407G>C]         na
2 c.29T>C p.Ile10Thr   Ile-8Thr Versailles lab June 2017 infantile c.[29T>C];[29T>C]         +
2 c.41T>C p.Leu14Pro   Leu-4Pro Versailles lab Jul 2010 adult c.[41T>C];[571G>A]         +
2 c.43_46delACTA p.Asn16Profs   pAsn-2Profs

Versailles lab March 2011
de Roo et al. 2014

infantile

infantile

c.[43_46delACTA];[668G>A]

        na
2 c.50C> T p.Ser17Phe P Ser-1Phe Mornet et al. 1998 infantile c.[50C> T];[223G>A] 19.0 Zurutuza et al. 1999     +
2 c.61G>A p.Glu21Lys P Glu4Lys Research center for medical genetics, Moscow, Apr. 2015 adult c.[.61G>A];[?]         ++
IVS2 c.62-1G>A       Versailles lab Feb. 2019 adult c.[62-1G>A];[=]         na
IVS2 c.62-1G>C   P   Versailles lab March 2013 perinatal c.[62-1G>C];[62-1G>C]         na
                         
3 c.69_74delGAAAGA       Versailles lab May 2012 perinatal c.[69_74delGAAAGA];[146A>T]         na
3 c.82T>G p.Tyr28Asp P Tyr11Asp Yang et al. 2013 odonto c.[82T>G];[1162T>C] 0 Yang et al. 2013

45

Yang et al. 2013 ++
3 c.83A>G p.Tyr28Cys P Tyr11Cys Taillandier et al. 2001 infantile c.[83A>G];[407G>A] 7.2 Taillandier et al. 2001     ++
3 c.85T>C p.Trp29Arg P Trp12Arg Chen et al. 2017 childhood c.[85T>C];[1559delT] 4.1 Chen et al. 2017 33.7 Chen et al. 2017 ++
3 c.88C>T p.Arg30* P Arg13Ter Versailles lab Dec 2010 perinatal c.[88C>T];[385G>A]         na
3 c.94C>T p.Gln32*   Gln15Ter Versailles lab. Apr 2011 perinatal c.[94C>T];[648+1G>A]         na
3 c.97G>C p.Ala33Pro   Ala16Pro University of Brasilia Lab, July 2016 infantile c.[97G>C;112A>G];[1307A>G]         +
3 c.98C>T p.Ala33Val P Ala16Val Henthorn et al. 1992 childhood c.[98C>T];[1306T>C]         +
3 c.106A>C p.Thr36Pro   Thr19Pro Versailles lab Nov 2008 perinatal c.[106A>C];[106A>C]         ++
3 c.110T>C p.Leu37Pro P Leu20Pro Versailles lab oct. 2003 perinatal c.[110T>C];[110T>C]         ++
3 c.[113_116delAATA ; 118_119insG] p.Lys38_Tyr39delinsMet   p.Lys21_Tyr22delinsMet Versailles lab Dec. 2017 adult c.[113_116delAATA;118_119insG];[=]         na
3 c.119C>T p.Ala40Val LP Ala23Val Mornet et al. 1998 perinatal c.[119C>T];[1417C>T] 2.3 Zurutuza et al. 1999 51.3 Lia-Baldini et al. 2001 +
3 c.129delT p.Gln44Argfs P Gln27Argfs Whyte et al. 2015 childhood c.[129delT];[1307A>G]         na
3 c.130C>T p.Gln44* P Gln27Ter Mornet E, unpublished perinatal c.[130C>T];[662insG]         na
3 c.140A>T p.Asn47Ile   Asn30Ile Saglam et al. 2017

perinatal

adult

c.[140A>T];[140A>T]

c.[140A>T];[=]

        ++
3 c.146A>T p.Asn49Ile   Asn32Ile Versailles lab May 2012 perinatal c.[69_74delGAAAGA];[146A>T]         +
3 c.151G>T p.Ala51Ser P Ala34Ser Mumm et al. 2002 infantile c.[151G>T];[400_401delinsAC>CA]         ++
3 c.152C>T p.Ala51Val P Ala34Val Taillandier et al. 2001 infantile c.[152C>T];[1375G>A]         ++
3 c.178G>C p.Asp60His VUS Asp43His McKiernan et al.2017 asymptomatic* c.[178G>C];[=]          
3 c.180T>G p.Asp60Glu P Asp43Glu Whyte et al. 2015 childhood c.[180T>G];[=]         ++
IVS3 c.182-2A>C   P   Whyte et al. 2015 childhood c.[182-2A>C];[=]         na
                         
4 c.184A>T p.Met62Leu P Met45Leu Taillandier et al. 1999 infantile c.[184A>T];[1172delC] 27.4 Zurutuza et al. 1999     ++
4 c.184A>G p.Met62Val P Met45Val Spentchian et al. 2003 infantile c.[184A>G];[184A>G]         ++
4 c.186G>C p.Met62Ile P Met45Ile Taillandier et al.2005 childhood c.[186G>C];[571G>A] 0 Taillandier et al.2005     ++
4 c.187G>C p.Gly63Arg P Gly46Arg Spentchian et al. 2003 infantile c.[187G>C];[187G>C]         ++
4 c.187_205del19 p.Gly63Leufs    

Versailles lab Jan 2010

Taillandier et al. 2017

adult c.[187_205del];[=]         na
4 c.188_205dup18 p.Gly63_Thr68dup P   Guanabens et al. 2013 adult c.[188_205dup18];[?]         na
4 c.188G>T p.Gly63Val P Gly46Val Lia-Baldini et al. 2001 infantile c.[188G>T];[=] 0.8 Lia-Baldini et al. 2001 26.0 Lia-Baldini et al. 2001 ++
4 c.194C>A p.Ser65Tyr   Ser48Tyr Saglam et al. 2017 perinatal c.[194C>A];[194C>A]          
4 c.203C>T p.Thr68Met P Thr51Met

Orimo et al. 2002

Mao et al.2019

childhood

childhood

c.[203C>T];[529G>A]

c.[203C>T];[571G>A]

5.2 Orimo et al. 2001     ++
4 c.202_204delACG p.Thr68del   Thr51del communicated by S. Lazarus, Royal Brisbane &Women's Hospital, Herston, Australia adult c.[202_204delACG];[=]         na
4 c.208G>A p.Ala70Thr VUS Ala53Thr communicated by Dr S. Brugger and T. Brown (Alexion) Mild form. Patient with low AP and unspecific symptoms c.[208G>A];[208G>A]         +
4 c.211C>T p.Arg71Cys P Arg54Cys Henthorn et al. 1992 infantile c.[211C>T];[811A>C] 0 Fukushi-Irié et al. 2000 35.0 Fauvert et al. 2009 ++
4 c.211C>G p.Arg71Gly P Arg54Gly

Research center for medical genetics, Moscow, June 2015

Tenorio et al. 2017

adult

 

childhood

c.[211C>G];[=]

 

c.[211C>G];[=]

        ++
4 c.211C>A p.Arg71Ser P Arg54Ser Orimo et al. 2002 childhood c.[211C>A];[?] 2.9 Orimo et al. 2001     ++
4 c.212G>C p.Arg71Pro P Arg54Pro Henthorn et al. 1992 perinatal c.[212G>C];[620A>C]         ++
4 c.212G>A p.Arg71His P Arg54His

Taillandier et al. 2001

Mao et al.2019

perinatal

childhood

c.[119C>T];[212G>A]

c.[212G>A];[571G>A]

1.0 Fauvert et al. 2009 30.5 Fauvert et al. 2009 ++
4 c.215T>C p.Ile72Thr P Ile55Thr Versailles lab oct. 2004 odonto c.[215T>C];[=] 5.1 Fauvert et al. 2009 40.2 Fauvert et al. 2009 ++
4 c.216A>G p.Ile72Val   Ile55Val Versailles lab dec. 2014 infantile c.[216A>G];[216A>G]         ++
4 c.217_219delCTC p.Leu73del   Leu56del

Versailles lab aug. 2013

Tenorio et al. 2017

asymptomatic*

childhood

c.[217_219delCTC];[=]

c.[217_219delCTC];[=]

        na
4 c.223G>A p.Gly75Ser P Gly58Ser Mornet et al. 1998 infantile c.[50C> T];[223G>A] 3.5 Zurutuza et al. 1999     ++
4 c.227A>G p.Gln76Arg P Gln59Arg Mornet et al. 2001 infantile c.[227A>G];[401C>A]         ++
4 c.228G>T p.Gln76His P                  
4 c.228delG   P   Li et al. 2017 infantile c.[228delG];[407G>A]         na
4 c.242delC p.Pro81Leufs   Pro64Leufs Versailles lab Jul 2009 perinatal c.[242delC];[242delC]         na
4 c.247G>T p.Glu83*   Glu66Ter Versailles lab Apr 2011 infantile c.[247G>T];[247G>T]         na
4 c.251A>T p.Glu84Val P Glu67Val Wei et al. 2010 odonto c.[251A>T];[?]         +
4 c.252G>C p.Glu84Asp   Glu67Asp Whyte et al. 2016 infantile c.[252G>C];[1375G>A]         +
4 c.262G>A p.Glu88Lys P Glu71Lys Mohn et al. 2011 infantile c.[262G>A];[920C>T]         ++
4 c.277C>T p.Pro93Ser LP Pro76Ser Peach et al. 2007 prenat. benign c.[277C>T];[400_401delinsAC>CA]         ++
4 c.283G>A p.Val95Met LP   Versailles lab Sept 2019 adult c.[283G>A];[=]         ++
4 c.297G>C p.Lys99Asn   Lys82Asn Seefried et al. 2017 adult c.[297G>C];[=]         ++
IVS4 c.297+2T>A       Clinvar (Counsyl) infantile not provided         na
IVS4 c.297+3G>T   LP   Versailles lab. Jan 2011 infantile c.297+3G>T;[299C>T]         na
IVS4 c.298-2A>G   P   Taillandier et al. 2000 perinatal c.[298-2A>G];[997+3A>C]         na
IVS4 c.298-1G>A   P   Zhang et al. 2012 adult c.[298-1G>A];[298-1G>A]         na
                         
5 c.299C>T p.Thr100Met P Thr83Met

Mornet et al. 2001

Michigami et al.2019

infantile

perinatal benign

c.[299C>T];[571G>A]

c.[299C>T];[928T>C]

1.3 Fauvert et al. 2009 28.2 Fauvert et al. 2009 ++
5 c.301T>G p.Tyr101Asp   Tyr84Asp Versailles lab. Feb 2012 odonto c.[301T>G];[=]         ++
5 c.303C>A p.Tyr101* P Tyr84Ter Alonso et al. 2019 adult with unspecific signs (osteoporosis) c.[303C>A];[=]         na
5 c.303_311del p.Asn102_Asn104del P Asn85_Asn87del Versailles lab Jul 2007 perinatal c.[303_311del];[1471G>A]         na
5 c.314C>A p.Ala105Asp   Ala88Asp Communicated by Sue Krug Soft Bones U.S. Oct. 2018 adult c.[314C>A];[=]         ++
5 c.317A>G p.Gln106Arg   Gln89Arg Communicated by Dr M.G. Benzrihen, Hospital Alejandro Posedas, Argentina childhood c.[317A>G];[=]         ++
5 c.318G>C p.Gln106His LP Gln89His Balasubramaniam et al. 2010 infantile c.[318G>C];[318G>C]         ++
5 c.323C>T p.Pro108Leu P Pro91Leu Herasse et al. 2003 odonto c.[323C>T];[=] 1.9 Fauvert et al. 2009 24.0 Fauvert et al. 2009 ++
5 c.327C>A p.Asp109Glu   Asp92Glu Bone Metabolism Unit, Instituto Auxologico Italiano IRCCS, Milano, Italy adult c.[327C>A];[327C>A]         ++
5 c.331G>A p.Ala111Thr P Ala94Thr Goseki-Sone et al. 1998 odonto c.[331G>A];[?] 2.0 Fauvert et al. 2009 48.7 Fauvert et al. 2009 ++
5 c.333delC p.Gly112Alafs P Gly95Alafs Bai et al. 2016 perinatal c.[333delC];[568_570delAAC]         na
5 c.334G>A p.Gly112Ser P Gly95Ser Witters et al. 2004 infantile c.[334G>A];[1171C>T]         ++
5 c.334G>C p.Gly112Arg P Gly95Arg Whyte et al. 2015 odonto. c.[334G>C];[=]         ++
5 c.335_340dupGCACCG p.Gly112_113dup P Gly95_96dup Wenkert et al. 2011 prenatal benign c.[335_340dupGCACCG];[571G>A]         na
5 c.340G>A p.Ala114Thr P Ala97Thr Mumm et al. 2001 infantile c.[340G>A];[811A>C]         ++
5 c.341C>G p.Ala114Gly P Ala97Gly Draguet et al. 2004 perinatal

c.[341C>G;348_349insACCGTC];[976G>C]

        ++
5 c.341C>T p.Ala114Val   Ala97Val Versailles lab march 2016 adult

c.[341C>T];[=]

        ++
5 c.344C>T p.Thr115Ile   Thr98Ile Versailles lab Feb. 2019 odonto c.[344C>T];[407G>A]         ++
5 c.346G>T p.Ala116Ser P Ala99Ser Versailles lab Jul 2007 adult c.[346G>T];[1250A>G]         ++
5 c.346G>A p.Ala116Thr P Ala99Thr Hu et al. 2000 adult c.[346G>A];[=] 0.8 Lia-Baldini et al. 2001 40.0 Lia-Baldini et al. 2001 ++
5 c.348_349insACCGTC p.Ala116_Tyr117insThrVal P Ala99_Tyr100insThrVal Draguet et al. 2004 perinatal c.[Ala116Gly+c.348_349insACCGTC];[976G>C]         na
5 c.343_348dupACCGCC p.Thr115_Ala116dup P


Thr98_Ala99dup Versailles lab March 2009
Tenorio et al. 2017

odonto

childhood

c.[348_349insACCGCC];[=]

c.[348_349insACCGCC];[=]

        na
5 c.350A>G p.Tyr117Cys P Tyr100Cys Whyte et al. 2009 childhood c.[350A>G];[400_401delinsAC>CA]         +
5 c.352C>A p.Leu118Met P Leu101Met Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[352C>A];[352C>A]         ++
5 c.358G>A p.Gly120Arg P Gly103Arg Mornet et al. 1998 perinatal c.[358G>A];[648+1G>A]         ++
5 c.359G>C p.Gly120Ala LP Gly103Ala Mao et al.2019 infantile c.[359G>C];[359G>C]       ++
5 c.360_361delGG p.Val121Glufs   Val104Glufs Vidmar et al. 2017 perinatal c.[360_361delGG];[46_49delAACT]         na
5 c.361G>A p.Val121Met   Val104Met Versailles lab dec. 2015

Lefever et al. 2018

childhood

adult

c.[361G>A];[=]

c.[361G>A];[=]

        ++
5 c.368C>A p.Ala123Asp P Ala106Asp Spentchian et al. 2006 perinatal c.[368C>A];[797_802del]         +
5 c.379A>G p.Thr127Ala   Thr110Ala Seefried et al. 2017 Adult c.[379A>G];[526G>A]         ++
5 c.382G>A p.Val128Met P Val111Met Mumm et al. 2002 perinatal c.[382G>A];[667C>T]         +
5 c.383_384insG p.Val130Glyfs   Val113Glyfs Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[383_384insG];[?]         na
5 c.385G>A p.Gly129Arg P Gly112Arg Mornet et al. 1998 perinatal c.[385G>A];[1471G>A]         ++
5 c.389_392delTAAG p.Val130Alafs   Val113Alafs Spentchian et al. 2003 perinatal c.[388_391delGTAA];[931G>A]         na
5 c.389delT p.Val130Glufs P Val113Glufs Spentchian et al. 2003 perinatal c.[389delT];[389delT]         na
5 c.392delG p.Ser131Thrfs P Ser114Thrfs Mumm et al. 2002 perinat/infant c.[392delG];[1042G>A]         na
5 c.394G>A p.Ala132Thr P Ala115Thr Versailles lab Jul 2006 adult c.[394G>A];[571G>A]         ++
5 c.395C>T p.Ala132Val P Ala115Val Watanabe et al. 2001 adult c.[395C>T];[?] 16.9 Watanabe et al. 2005     ++
5 c.400_401delinsAC>CA p.Thr134His P Thr117His Mumm et al. 2002 perinatal c.[400_401delinsAC>CA];[984_986delCTT]         +
5 c.401C>A p.Thr134Asn P Thr117Asn Taillandier et al. 2000 perinatal c.[401C>A];[401C>A] 20.5 Taillandier et al. 2000     +
5 c.406C>T p.Arg136Cys P Arg119Cys Versailles lab oct. 2003 odonto c.[406C>T];[407G>A]         ++
5 c.407G>A p.Arg136His P Arg119His Taillandier et al. 1999 infantile c.[407G>A];[485G>T] 33.4 Zurutuza et al. 1999 70.0 Fauvert et al. 2009 ++
5 c.407G>T p.Arg136Leu P Arg119Leu Yang et al. 2013 childhood c.[407G>T];[1166C>A] 35 Yang et al. 2013

62

Yang et al. 2013 ++
5 c.407G>C p.Arg136Pro P Arg119Pro Cui et al. 2012 infantile c.[18delA];[407G>C]         ++
5 c.412_413dupC p.Arg138Profs   Arg121Profs Xu et al. 2018 childhood c.[412_413dupC];[=]         na
5 c.413G>C p.Arg138Pro   Arg121Pro Castells et al. 2018 perinatal c.[413G>C];[473-2G>C]
c.473-2G>C probable error
        +
5 c.416G>A p.Cys139Tyr   Cys122Tyr Collagen Diagnosis Laboratory, University of Washington, USA, Febr. 2018 childhood c.[416G>A];[=]         ++
5 c.422C>A p.Thr141Asn P Thr124Asn Whyte et al. 2015 childhood c.[422C>A];[629A>G]         ++
5 c.422C>T p.Thr141Ile P Thr124Ile Versailles lab Jul 2008 infantile c.[422C>T];[920C>T]         ++
5 c.427delC p.Gln143Argfs P Gln126Argfs Whyte et al. 2015 childhood c.[427delC];[1444C>A]         na
5 c.431G>A p.Gly144Glu   Gly127Glu Versailles lab April 2018 adult c.[431G>A];[=]         ++
5 c.436G>A p.Glu146Lys VUS Glu129Lys Nielson et al. 2012

Alonso et al. 2019
asymptomatic*, low BMD

adult with unspecific signs (osteoporosis)
c.[436G>A];[=]         ++
5 c.442A>G p.Thr148Ala P Thr131Ala Michigami et al. 2005 perinatal c.[442A>G];[?]         ++
5 c.443C>T p.Thr148Ile P Thr131Ile Spentchian et al. 2003 infantile c.[443C>T];[484G>A]         ++
5 c.454C>T p.Arg152Cys P Arg135Cys

Versailles lab Nov. 2009

Martins et al. 2013

adult

odonto

c.[454C>T];[550C>T]

c.[454C>T];[1318_1320delAAC]

        +
5 c.457T>C p.Trp153Arg P Trp136Arg Wenkert et al. 2011 prenatal benign c.[1183A>G];[457T>C]         ++
5 c.461C>T p.Ala154Val   Ala137Val Yu et al. 2019 perinatal c.[461C>T];[406C>T]         ++
5 c.466G>T p.Asp156Tyr   Asp139Tyr Taillandier et al. 2017 Adult c.[466G>T];=]         +
IVS5 c.472+1G>A   P   Liu et al. 2010 odonto c.[472+1G>A];[1120G>A]         na
IVS5 c.473-2A>G   P   Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[473-2A>G];[?]         na
                         
6 c.480delT   P   Versailles lab. Jan. 2008 perinatal c.[480delT];[667C>T]         na
6 c.484G>A p.Gly162Ser P Gly145Ser Spentchian et al. 2003 infantile c..[443C>T];[484G>A]         ++
6 c.485G>T p.Gly162Val P Gly145Val Taillandier et al. 1999 infantile c.[407G>A];[485G>T] 1.3 Zurutuza et al. 1999     ++
6 c.491T>G p.Val164Gly   Val147Gly Versailles lab March 2009 infantile c.[491T>G];[811A>C]         ++
6 c.494C>T p.Thr165Ile   Thr148Ile Versailles lab April 2018 adult c.[494C>T];[=]         ++
6 c.497C>T p.Thr166Ile P Thr149Ile Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[497C>T];[=]         ++
6 c.500C>T p.Thr167Met P Thr150Met

Versailles lab Oct. 2003
Braunstein et al. 2015

infantile

adult

c.[500C>T];[571G>A]

c.[500C>T];[=]

0       +
6 c.508A>G p.Asn170Asp P Asn153Asp Mornet et al. 1998 perinatal c.[508A>G];[508A>G] 0 Ito et al. 2002     +
6 c.511C>T p.His171Tyr P His154Tyr Taillandier et al. 1999 infantile c.[511C>T];[571G>A] 2.1 Zurutuza et al. 1999     ++
6 c.512A>G p.His171Arg P His154Arg Bükmann Larsen et al. 2018 adult c.[512A>G];[571G>A]         ++
6 c.518C>T p.Thr173Ile   Thr156Ile C.V. Lago, Military Police Hospital M.G., Belo Horizonte, Brazil, July 2017 childhood c.[518C>T];[=]         ++
6 c.522delC p.Ser175Alafs   Ser158Alafs Clinvar (Counsyl) infantile not provided         na
6 c.526G>A p.Ala176Thr P Ala159Thr Taillandier et al. 2000 childhood c.[526G>A];[738G>T] 45.4 Taillandier et al. 2000 58.0 Fauvert et al. 2009 ++
6 c.529G>A p.Ala177Thr P Ala160Thr Goseki-Sone et al. 1998 adult c.[529G>A];[979T>C] 83.8 Orimo et al. 2001     +
6 c.532T>C p.Tyr178His P Tyr161His Ikenoue et al. 2017 perinatal c.[532T>C];[1559delT] 0 Ikenoue et al. 2017     ++
6 c.535G>A p.Ala179Thr P Ala162Thr Weiss et al. 1988 perinatal c.[535G>A]:[535G>A] 18 Shibata et al.1998     ++
6 c.538C>A p.His180Asn   His163Asn Versailles lab March 2016
Lefever et al. 2018
adult c.[538C>A];[=]         ++
6 c.539A>G p.His180Arg   His163Arg Versailles lab Dec. 2018 adult c.[539A>G];[=]         ++
6 c.542C>T p.Ser181Leu P Ser164Leu Lia-Baldini et al. 2001 infantile c.[542C>T];del(ex12) 1.3 Lia-Baldini et al. 2001 54.4 Lia-Baldini et al. 2001 ++
6 c.544delG p.Ala182Leufs P Ala165Leufs Taillandier et al. 1999 perinatal c.[544delG];[746G>T]         na
6 c.547G>C p.Asp183His P Asp166His Versailles lab Nov 2008 infantile c.[547G>C];[811A>C]         +
6 c.550C>T p.Arg184Trp P Arg167Trp

Mornet et al. 1998

Michigami et al.2019

perinatal

odonto

c.[550C>T];[809G>A]

c.[550C>T];[?]

0.6

0

Lia-Baldini et al. 2001

Michigami et al.2019

36.7

50

Lia-Baldini et al. 2001

Michigami et al.2019

++
6 c.551G>A p.Arg184Gln   Arg167Gln Versailles lab. Nov. 2013 infantile c.[551G>A];[203C>T]         ++
6 c.558G>A p.Trp186*   Trp169* Garcia-Fontana et al. 2019 Adult c.[558G>A];[=]         na
6 c.562T>C p.Ser188Pro P Ser171Pro Oyachi et al. 2018 perinatal c.[562T>C];[1559delT]         ++
6 c.565G>A p.Asp189Asn   Asp172Asn communicated by A. O'Brien, Sick Kids Hospital, Toronto, Canada, April 2018 Adult c.[565G>A];[=]         ++
6 c.565_575delinsAG p.Asp189_Met192delinsArg   Asp172_Met175delinsArg Dr I. RAU , Institüt für Humangenetik, Hamburg, Germany, Jan 2019 Adult c.[565_575delinsAG];[=]         na
6 c.567C>A p.Asp189Glu P Asp172Glu Spentchian et al. 2003 perinatal c.[567C>A];[567C>A]         ++
6 c.568_570delAAC p.Asn190del P Asn173del Michigami et al. 2005 perinatal c.[568_570delAAC];[1559delT]         na
6 c.571G>A p.Glu191Lys P Glu174Lys

Henthorn et al. 1992

Mao et al.2019

Mao et al.2019

Versailles lab Jul 2010

infantile

childhood

childhood

adult

c.[571G>A];[1133A>T]

c.[203C>T];[571G>A]

c.[212G>A];[571G>A]

c.[41T>C];[571G>A]

88.0 Zurutuza et al. 1999 79.5 Fauvert et al. 2009 ++
6 c.572A>G p.Glu191Gly   Glu174Gly

Goseki-Sone et al. 1998

Michigami et al.2019

Michigami et al.2019

odonto

odonto

perinatal benign

c.[572A>G];[1559delT]

c.[572A>G];[1559delT]

c.[572A>G];[1559delT]

        ++
6 c.575T>C p.Met192Thr P Met175Thr


Versailles lab Jul 2007

Alonso et al. 2019

A.Rosen, Emory University, Atlanta GA, USA. Jan 2020

infantile

adult with unspecific signs (osteoporosis)

childhood (mild form)

c.[575T>C];[931G>A]

c.[575T>C];[=]

c.[575T>C];[=]

        ++
6 c.577C>G p.Pro193Ala P Pro176Ala Mumm et al. 2002 adult c.[340G>A];[577C>G]         +
6 c.599G>A p.Gly200Asp P Gly183Asp Taillandier et al. 2015 adult c.[599G>A];[=]         ++
6 c.601T>C p.Cys201Arg   Cys184Arg Xu et al. 2018 adult c.[601T>C];[=]         ++
6 c.602G>A p.Cys201Tyr P Cys184Tyr Taillandier et al. 1999 perinatal c.[-195C>T];[602G>A] 0 Satou et al. 2012     ++
6 c.609C>G p.Asp203Glu P Asp186Glu Versailles lab oct. 2004 perinatal c.[609C>G];[609C>G]         ++
6 c.614C>T p.Ala205Val   Ala188Val Versailles lab aug. 2013 asymptomatic* c.[614C>T];[?]         +
6 c.620A>C p.Gln207Pro P Gln190Pro Henthorn et al. 1992 perinatal c.[212G>C];[620A>C]         ++
6 c.622C>T p.Leu208Phe   Leu191Phe Versailles lab april 2009 perinatal c.[622C>T];[622C>T]         ++
6 c.625A>T p.Met209Leu VUS Met192Leu Schmidt et al. 2019 adult c.[625A>T];[746G>T]         +
6 c.629A>G p.His210Arg P His193Phe Whyte et al. 2015 childhood c.[422C>A];[629A>G]         +
6 c.630_637dupTAACATCA p.Arg213Ilefs   Arg196Ilefs Versailles lab June 2011 perinatal c.[630_637dupTAACATCA];[792G>A]         na
6 c.631A>G p.Asn211Asp P Asn194Asp Taillandier et al. 2001 infantile c.[346G>A];[631A>G]         ++
6 c.634A>T p.Ile212Phe P Ile195Phe Souka et al. 2002 perinatal c.[634A>T];[1062G>C]         +
6 c.644T>C p.Ile215Thr   Ile198Phe Versailles lab. march 2011 infantile c.[542C>T];[644T>C]         ++
IVS6 c.648+1G>T   P   Brun-Heath et al. 2005 perinatal c.[648+1G>T];[811A>C]         na
IVS6 c.648+1G>A   P   Mornet et al. 1998 perinatal c.[358G>A];[648+1G>A]         na
IVS6 c.648+2dupT      

Versailles lab jan 2013

Mentrup et al.2016

perinatal c.[648+2dupT];[1196C>T]         na
IVS6 c.649-1_3delinsAA       Versailles lab Jul 2006 perinatal c.[649-1_3delinsAA];[649-1_3delinsAA]         na
                         
7 c.650delTinsCTAA p.217delValinsAlaLys   200delValinsAlaLys Chang et al. 2011 perinatal c.[650delTinsCTAA];[984_986delCTT]         na
7 c.653T>C p.Ile218Thr P Ile201Thr

Utsch et al., 2009

perinatal c.[653T>C];[1171C>T] 3.7 Utsch et al., 2009     ++
7 c.655A>G p.Met219Val P Met202Val Yang et al. 2013 odonto c.[655A>G];[331G>A] 75 Yang et al. 2013

80

Yang et al. 2013 +
7 c.657G>T p.Met219Ile   Met202Ile Versailles lab, Jan 2019 adult c.[657G>T];[=]         +
7 c.658G>A p.Gly220Arg P Gly203Arg Versailles lab Dec 2011 perinatal c.[658G>A];[658G>A]         ++
7 c.659G>T p.Gly220Val   Gly203Val Taillandier et al. 2001 odonto c.[571G>A];[659G>T]         ++
7 c.659G>C p.Gly220Ala P Gly203Ala Spentchian et al. 2003 perinatal c.[659G>C];[659G>C]         ++
7 c.661G>C p.Gly221Arg P Gly204Arg Versailles lab March 2009 perinatal c.[661G>C];[?]         ++
7 c.662dupG p.Gly222Trpfs   Gly205Trpfs Mornet E, unpublished perinatal c.[130C>T];[662_663insG]         na
7 c.662delG p.Gly221Valfs P Gly204Valfs Spentchian et al. 2003 perinatal c.[662delG];[815G>T]         na
7 c.662G>T p.Gly221Val P Gly204Val Versailles lab oct. 2004 perinatal c.[662G>T];[1064T>C]         ++
7 c.667C>T p.Arg223Trp P Arg206Trp Mornet et al. 1998 perinatal c.[667C>T];[?] 2.8 Lia-Baldini et al. 2001 51.9 Lia-Baldini et al. 2001 ++
7 c.668G>A p.Arg223Gln P Arg206Gln Mumm et al. 2002

perinatal

infantile

c.[668G>A];[0]

c.[668G>A];[881A>C]

2.9 Zhu et al. 2012     ++
7 c.670A>G p.Lys224Glu P Lys207Glu Mochizuki et al. 2000 infantile c.[670A>G];[1276G>T] 43 Michigami et al. 2005     ++
7 c.677T>C p.Met226Thr P Met209Thr Baumgartner-Sigl et al. 2007 infantile c.[677T>C];[1112C>T]         ++
7 c.704A>T p.Glu235Val   Glu218Val Michigami et al.2019 odonto c.[704A>T];[1559delT]          
7 c.704A>G p.Glu235Gly P Glu218Gly Taillandier et al. 2001 adult c.[704A>G];[1195G>T] 3.6 Mornet et al. 2001     ++
7 c.715G>T p.Asp239Tyr   Asp222Tyr Saraff et al. 2016 asymptomatic* c.[715G>T];[715G>T]         +
7 c.734C>T p.Thr245Met   Thr228Met Versailles lab May 2016 prenatal benign? (not confirmed) c.[734C>T];[?]         ++
7 c.738G>T p.Arg246Ser   Arg229Ser Taillandier et al. 2000 childhood c.[526G>A];[738G>T] 4.4 Taillandier et al. 2000     ++
7 c.746G>T p.Gly249Val P Gly232Val Fedde et al. 1996 perinatal c.[746G>T];[746=] 34.5 Lia-Baldini et al. 2001 70.5 Lia-Baldini et al. 2001 +
7 c.791A>G p.Lys264Arg P Lys247Arg Brun-Heath et al. 2007 perinatal c.[791A>G];[1133A>T]         +
7 c.792G>A p.Lys264Lys   Lys247Lys Versailles lab june 2011 perinatal c.[792G>A];[630_637dupTAACATCA]         na (splice)
IVS7 c.793-14_33del       Mentrup et al. 2016 infantile c.[793-14_33del];[793-14_33del] 0 Mentrup et al. 2016 50 Mentrup et al. 2016 na
                         
8 c.797_802del p.Ser266_His267del P Ser249_His250del Spentchian et al. 2006 perinatal c.[368C>A];[797_802del]         na
8 c.799_804delCACTCC p.His267_Phe268del P p.His250_Phe251del Saglam et al. 2017 perinatal c.[799_804delCACTCC];[799_804delCACTCC]         na
8 c.809G>A p.Trp270* P Trp253* Mornet et al. 1998 perinatal c.[550C>T];[809G>A] 1.2 Zurutuza et al. 1999     na
8 c.814C>T p.Arg272Cys P Arg255Cys Spentchian et al. 2006 perinatal c.[814C>T];[400_401delinsAC>CA]         ++
8 c.814delC p.Arg272Alafs   Arg255Alafs Versailles lab June 2011 perinatal c.[814delT];[1142A>G]         na
8 c.815G>T p.Arg272Leu P Arg255Leu Spentchian et al. 2003 perinatal c.[815G>T];[662delG]         ++
8 c.815G>A p.Arg272His P Arg255His Brun-Heath et al. 2005 infantile c.[815G>A];[815G>A] 6.8 Brun-Heath et al. 2005     ++
8 c.824T>C p.Leu275Pro P Leu258Pro Orimo et al. 2002 childhood c.[824T>C];[529G>A] 3.3 Orimo et al. 2001     ++
8 c.841delC p.His281Thrfs   His264Thrfs Clinvar (Counsyl) infantile not provided         na
8 c.850_853dupGACT p.Tyr285*   Tyr268* Michigami et al. 2005 perinatal c.[850_853dupGACT];[1559delT]         na
IVS8 c.862+5G>A   P   Taillandier et al. 1999 infantile c.[862+5G>A];[c.862+5G>A]         na
                         
9 c.865C>T p.Leu289Phe P Leu272Phe Sugimoto et al. 1998 infantile c.[865C>T];[1559delT] 50 Sugimoto et al. 1998     ++
9 c.868_869delTT p.Phe290fs LP Phe273fs Versailles lab Sept 2019 adult c.[868_869delTT];[=]         na
9 c.871G>A p.Glu291Lys P Glu274Lys Mornet et al. 1998 infantile c.[571G>A];[871G>A] 8.3 Zurutuza et al. 1999     ++
9 c.871G>T p.Glu291* P Glu274Ter Taillandier et al. 2000 perinatal c.[331G>A];[871G>T]         na
9 c.871G>C p.Glu291Gln   Glu274Gln Versailles lab Jun 2010 perinatal c.[871G>C];[871G>C]         ++
9 c.874C>A p.Pro292Thr P Pro275Thr Brun-Heath et al. 2005 infantile c.[98C>T];[874C>A] 4.0 Brun-Heath et al. 2005     ++
9 c.874C>T p.Pro292Ser P Pro275Ser Tenorio et al. 2017   c.[815G>T];[874C>T]         ++
9 c.875_881delCAGGGGAinsT   P   Belachew et al. 2013 perinatal c.[875_881delCAGGGGAinsT];[1559delT]         na
9 c.876_881delAGGGGA p.Gly293_Asp294del P Gly276_Asp277del Spentchian et al. 2003 perinatal c.[876_881delAGGGGA];[962delG]         na
9 c.880G>T p.Asp294Tyr P Asp277Tyr Taillandier et al. 2001 infantile c.[526G>A];[880G>T]         ++
9 c.881A>C p.Asp294Ala P Asp277Ala

Henthorn et al. 1992

Mumm et al. 2002

infantile

infantile

c.[211C>T];[881A>C]

c.[668G>A];[881A>C]

35 Fukushi-Irié et al. 2000     ++
9 c.883A>G p.Met295Val P Met278Val Mornet et al. 2001 childhood c.[571G>A];[883A>G]         +
9 c.884T>C p.Met295Thr P Met278Thr Brun-Heath et al. 2005 perinatal c.[884T>C;[667C>T] 8.5 Brun-Heath et al. 2005     +
9 c.885G>A p.Met295Ile P Met278Ile Michigami et al. 2005 perinatal c.[885G>A];[1559delT]         +
9 c.886C>T p.Gln296*   Gln279* Plendl et al. 2011 adult c.[886C>T];[?]         na
9 c.889T>G p.Tyr297Asp P Tyr280Asp Brun-Heath et al. 2005 childhood c.[407G>A];[889T>G] 1.3 Brun-Heath et al. 2005     ++
9 c.889T>C p.Tyr297His P Tyr280His Bertola et al. 2009 perinatal c.[648+1G>A];[889T>C]         ++
9 c.889T>A p.Tyr297Asn   Tyr280Asn Research center for medical genetics, Moscow, Oct. 2015 childhood c.[889T>A];[?]         ++
9 c.891C>A p.Tyr297* P Tyr280* Balasubramaniam et al. 2010 infantile c.[891C>A];[1471G>A]         na
9 c.892G>A p.Glu298Lys P Glu281Lys Orimo et al. 1994 infantile c.[892G>A];[1559delT]         ++
9 c.896T>C p.Leu299Pro P Leu282Pro Versailles lab oct. 2003 infantile c.[896T>C];[896T>C] 9.7 Michigami et al. 2005     ++
9 c.901A>T p.Arg301Trp LP Arg284Trp Alonso et al. 2019 adult with unspecific signs (osteoporosis) c.[901A>T];[=]         ++
9 c.902delG p.Asn302Thrfs   p.Asn285Thrfs Research center for medical genetics, Moscow, Nov. 2016 childhood c.[902delG];[?]         na
9 c.917A>T p.Asp306Val P Asp289Val Taillandier et al. 1999 infantile c.[917A>T];[917A>T] 0 Ishida et al. 2003     ++
9 c.919C>T p.Pro307Ser P Pro290Val Versailles lab oct. 2004 infantile c.[919C>T];[1400T>C]         ++
9 c.920C>T p.Pro307Leu LP Pro290Leu Versailles lab Jul. 2006

Alonso et al. 2019
childhood

adult with unspecific signs (osteoporosis)

c.[920C>T];[542C>T]


c.[920C>T];[=]

        ++
9 c.928_929delTC p.Ser310Argfs P Ser293Argfs Brun-Heath et al. 2005 perinatal c.[928_929delTC];[1231A>G]         na
9 c.931G>A p.Glu311Lys P Glu294Lys Spentchian et al. 2003 perinatal c.[388_391delGTAA];[931G>A]         ++
9 c.952C>T p.Gln318*   Gln301* Versailles lab Dec 2011 perinatal c.[952C>T];[1216G>A]         na
9 c.962delG p.Lys322Argfs P Lys305Argfs Spentchian et al. 2003 perinatal c.[876_881delAGGGGA];[962delG]         na
9 c.968A>T p.Asn323Ile   Asn306Ile City Hospital #40, St Petersburg, Russia childhood c.[968A>T];[?]         ++
9 c.969C>G p.Asn323Lys   Asn306Lys Versailles lab oct. 2009 childhood c.[648+1G>A];[969C>G]         ++
9 c.976G>C p.Gly326Arg P Gly309Arg Litmanovitz et al. 2002 perinatal c.[976G>C];[871G>A]]         ++
9 c.977G>T p.Gly326Val P Gly309Val Versailles lab Jul 2008 perinatal c.[977G>T];[977G>T]         ++
9 c.980T>G p.Phe327Cys P Phe310Cys

Mornet et al. 2001

McKiernan et al.2017

perinatal

asymptomatic*

c.[401C>A];[980T>G]

c.[980T>G];[=]

        ++
9 c.979_980TT>GG p.Phe327Gly P Phe310Gly Taillandier et al. 2001 adult c.[571G>A];[979_980TT>GG]         ++
9 c.979T>C p.Phe327Leu P Phe310Leu

Ozono et al. 1996

Mao et al.2019

Michigami et al.2019

infantile

odonto

odonto

c.[979T>C];[1366G>A]

c.[979T>C];[1017dupG]

c.[979T>C];[1559delT]

72 Cai et al. 1998     ++
9 c.982T>C p.Phe328Leu P Phe311Leu Michigami et al. 2005 perinatal benign c.[299C>T];[982T>C] 10 Michigami et al. 2005     ++
9 c.984_986delCTT p.Phe327del P Phe311del

Orimo et al. 1997

infantile

c.[984_986delCTT];[1559delT]

10 Michigami et al. 2005     na
IVS9 c.997+1G>T   P   Liu et al. 2010 odonto c.[997+1G>T];[1162T>C]         na
IVS9 c.997+2T>A   P   Taillandier et al. 2000 perinatal c.[997+2T>A];[1466G>C]         na
IVS9 c.997+2T>G   P   Brun-Heath et al. 2005 perinatal c.[997+2T>G];[997+2T>G]         na
IVS9 c.997+3A>C   P   Mornet et al. 1998 perinatal c.[997+3A>C];[997+3A>C]         na
IVS9 c.997+3A>G   P   Wenkert et al. 2011 prenatal benign c.[997+3A>G];[1181_1182delCT]         na
IVS9 c.998-2A>G       Clinvar (Counsyl) infantile not provided         na
IVS9 c.998-1G>T   P   Taillandier et al. 2001 perinatal c.[571G>A];[998-1G>T]         na
                         
10 c.1000G>C p.Gly334Arg P Gly317Arg Fauvert et al. 2009 odonto c.[1000G>C];[=] 5.0 Fauvert et al. 2009 39.0 Fauvert et al. 2009 ++
10 c.1001G>A p.Gly334Asp P Gly317Asp Greenberg et al. 1993 perinatal c.[1001G>A];[1001G>A] 0 Fukushi et al. 1998 40.0 Fauvert et al. 2009 ++
10 c.1004G>C p.Arg335Thr   Arg318Thr Institute of Human Genetics, UK Hamburg-Eppendorf, Germany adult c.[1004G>C];[=]         ++
10 c.1010A>G p.Asp337Gly P Asp320Gly Whyte et al. 2015 childhood c.[571G>A];[1010A>G]         ++
10 c.1015G>A p.Gly339Arg   Gly322Arg Mumm et al. 2002 perinatal c.[526G>A];[1015G>A] 1.1 Fauvert et al. 2009 33.0 Fauvert et al. 2009 ++
10 c.1015G>C p.Gly339Arg P Gly322Arg Versailles lab. Jan 2010 adult c.[571G>A];[1015G>A]         ++
10 c.1016G>A p.Gly339Glu P Gly322Glu Versailles lab oct. 2004 infantile c.[382G>A];[1016G>A]         ++
10 c.1017dupG p.His340Alafs P p.His323Alafs Mao et al.2019 odonto c.[979T>C];[1017dupG]         na
10 c.1022A>G p.His341Arg P His324Arg Versailles lab Dec. 2018 prenatal benign (likely) c.[1022A>G];[?]         ++
10 c.1039C>T p.Gln347* P Gln330* Park et al. 2016 infantile c.[334G>A];[1039C>T]         na
10 c.1042G>A p.Ala348Thr P Ala331Thr Taillandier et al. 2000 infantile c.[571G>A];[1042G>A] 33.2 Taillandier et al. 2000     ++
10 c.1044_1055del12 p.Leu349_Ala352del P Leu332_Ala335del Spentchian et al. 2006 perinatal c.[1044_1055del12];[1471G>A]         na
10 c.1062G>C p.Glu354Asp P Glu337Asp Souka et al. 2002 perinatal c.[634A>T];[1062G>C]         ++
10 c.1064T>C p.Met355Thr P Met338Thr Versailles lab oct. 2004 perinatal c.[662G>T];[1064T>C]         ++
10 c.1065G>A p.Met355Ile P Met338Ile Versailles lab. Jan. 2008 infantile c.[1065G>A];[1171C>T]         ++
10 c.1068C>G p.Asp356Glu VUS Asp339Glu McKiernan et al.2017 asymptomatic* c.[1068C>G];[=]          
10 c.1068C>A p.Asp356Glu VUS Asp339Glu Versailles lab Apr 2011 perinatal c.[668G>A];[1068C>A]         ++
10 c.1070G>T p.Arg357Leu   Arg340Leu Nielson et al. 2012 asymptomatic*, low BMD

c.[1070G>T];[?]

        +
10 c.1072G>A p.Ala358Thr   Ala 341Thr Research center for medical genetics, Moscow, Nov. 2015 adult c.[1072G>A];[?]         ++
10 c.1077C>G p.Ile359Met P Ile342Met Whyte et al. 2012 infantile c.[1077C>G];[1133A>T]         ++
10 c.1083_1084dup p.Ser364Argfs   Ser347Argfs Riancho-Zarrabeitia et al. 2016 asymtomatic* or very mild symptoms c.[1083_1084dup];[?]         na
10 c.1088_1091dup p.Ser364Argfs P Ser347Argfs

Clinvar (Counsyl)

infantile

not provided

        na
10 c.1097C>A p.Thr366Asn   Thr349Asn Versailles lab march 2016 asymtomatic* or very mild symptoms c.[1097C>A];[?]         ++
10 c.1101_1103delCTC p.Ser368del P Ser351del Versailles lab oct. 2004 perinatal c.[1101_1103delCTC];[1166C>T]         na
10 c.1112C>T p.Thr371Ile P Thr354Ile Baumgartner-Sigl et al. 2007 infantile c.[677T>C];[1112C>T]         ++
10 c.1120G>A p.Val374Met P Val357Met Versailles lab oct. 2004

Alonso et al. 2019
adult

adult with unspecific signs (osteoporosis)
c.[892G>A];[1120G>A]


c.[1120G>A];[=]
57.6 Zhu et al. 2012     +
10 c.1130C>T p.Ala377Val P Ala360Val Mornet et al. 2001 perinatal c.[1130C>T];[1130C>T] 0 Michigami et al.,2019 50 Michigami et al.,2019 ++
10 c.1132G>T p.Asp378Tyr   Asp361Tyr Versailles lab. Apr. 2010 odonto. c.[1132G>T];[=] 0 Michigami et al.,2019   Michigami et al.,2019 ++
10 c.1132G>C p.Asp378His P Asp361His Whyte et al. 2015 childhood c.[571G>A];[1132G>C]         ++
10 c.1133A>T p.Asp378Val P Asp361Val

Henthorn et al. 1992

infantile

c.[571G>A];[1133A>T]

1.2 Lia-Baldini et al. 2001 19.9 Lia-Baldini et al. 2001 ++
10 c.1133A>G p.Asp378Gly P Asp361Gly Tenorio et al. 2017   c.[1133A>G];[571G>A]         ++
10 c.1135C>A p.His379Asn P His362Asn Dr Ivan Iglesias-Baena, CEO GenActive Clinic & Research, C / Madrid 79, Monachil, 18193, Granada, Spain. info@genactive.es adult c.[1135C>A];[=]         ++
10 c.1142A>G p.His381Arg P His364Arg

Taillandier et al. 2000

infantile c.[119C>T];[1142A>G]         ++
10 c.1144G>A p.Val382Ile P Val365Ile

Goseki-Sone et al. 1998

childhood

c.[979T>C];[1144G>A]

0 Watanabe et al. 2002 30.0 Takinami et al. 2004 ++
10 c.1162T>C p.Tyr388His P Tyr371His

Liu et al. 2010

Yang et al. 2013

odonto

odonto

c.[997+1G>T];[1162T>C]

c.[82T>G];[1162T>C]

39.7 Zhu et al. 2012 60 Yang et al. 2013 ++
10 c.1166C>T p.Thr389Ile P Thr372Ile Versailles lab oct. 2004 perinatal c.[1101_1103delCTC];[1166C>T]         ++
10 c.1166C>A p.Thr389Asn P Thr372Asn Yang et al. 2013 childhood c.[407G>T];[1166C>A] 0 Yang et al. 2013

40

Yang et al. 2013 ++
10 c.1171C>T p.Arg391Cys P Arg374Cys Zurutuza et al. 1999 childhood c.[571G>A];[1171C>T] 10.3 Zurutuza et al. 1999 50.5 Fauvert et al. 2009 ++
10 c.1172G>A p.Arg391His P Arg374His Orimo et al. 2002 childhood c.[1172G>A];[?] 3.7 Orimo et al. 2001 29.1 Fauvert et al. 2009 ++
10 c.1171delC p.Arg391Valfs P Arg374Valfs

Taillandier et al. 1999

infantile

c.[184A>T];[1172delC]

        na
10 c.1175G>C p.Gly392Ala P Gly375Ala Versailles lab. Jan. 2008 perinatal c.[1175G>C];[406C>T]         ++
10 c.1178A>T p.Asn393Ile   Asn376Ile Versailles lab March 2013 infantile moderate c.[571G>A];[1178A>T]         +
10 c.1181_1182delCT p.Ser394fs P Ser377fs Wenkert et al. 2011 prenatal benign c.[997+3A>G];[1181_1182delCT]         na
10 c.1182dup p.Ile395fs   Ile395fs communicated by Dr Rhonda Singhapong (Alexion) adult c.[1182dup] ;[=]         na
10 c.1183A>G p.Ile395Val P Ile378Val

Wenkert et al. 2011

Katsuyuki et al. 2019

prenatal benign

childhood

c.[1183A>G];[457T>C]

c.[1183A>G];[1559delT]

19 Chen et al. 2017 50 Chen et al. 2017 ++
10 c.1184T>C p.Ile395Thr P Ile378Thr Versailles lab Jul. 2006 perinatal c.[1184T>C];[571G>A]         ++
IVS10 c.1189+5delG   P   Whyte et al. 2015 childhood c.[1189+5delG];[1328C>T]         na
                         
11 c.1190G>A p.Gly397Asp P Gly380Asp

Whyte et al. 2015

odonto.

c.[1190G>A];[=]

        ++
11 c.1190G>T p.Gly397Val   Gly380Asp Versailles lab Dec. 2019 childhood (moderate) c.[1190G>T];[=]         ++
11 c.1195G>T p.Ala399Ser P Ala382Ser Taillandier et al. 2001 adult c.[704A>G];[1195G>T]         ++
11 c.1196C>T p.Ala399Val P Ala382Val Spentchian et al. 2006 adult c.[98C>T];[1196C>T]         ++
11 c.1199C>T p.Pro400Leu P Pro383Leu Spentchian et al. 2006 infantile c.[1199C>T];[1199C>T]         ++
11 c.1214_1215delCA p.Thr405Argfs P Thr388Argfs Versailles lab Jul. 2006 adult c.[571G>A];[1214_1215delCA]         na
11 c.1216_1219delGACA p.Asp406Argfs P Asp389Argfs Brun-Heath et al. 2005 perinatal c.[1216_1219delGACA];[?]         na
11 c.1216G>A p.Asp406Asn   Asp389Asn Versailles lab Dec 2011 perinatal c.[952C>T];[1216G>A]         -
11 c.1217A>G p.Asp406Gly P Asp389Gly Taillandier et al. 2000 odonto. c.[1217A>G];[1349G>A] 14.9 Taillandier et al. 2000     -
11 c.1228T>C p.Phe410Leu P Phe393Leu Versailles lab oct. 2004 infantile c.[571G>A];[1228T>C]         +
11 c.1231A>G p.Thr411Ala P Thr394Ala Brun-Heath et al. 2005 perinatal c.[928_929delTC];[1231A>G] 0.3 Brun-Heath et al. 2005     ++
11 c.1238T>C p.Ile413Thr   p.Ile396Thr University of Brasilia Lab, July 2016 childhood c.[1238T>C];[?]         ++
11 c.1240C>A p.Leu414Met P Leu397Met Mumm et al. 2002 perinatal c.[1240C>A];[811A>C] 0.4 Fauvert et al. 2009 23.5 Fauvert et al. 2009 ++
11 c.1243T>G p.Tyr415Asp   Tyr398Asp Saglam et al. 2017 perinatal c.[1243T>G];[1243T>G]         ++
11 c.1250A>G p.Asn417Ser P Asn400Ser

Sergi et al. 2001

perinatal

c.[1250A>G];[648+1G>A]

3 Fauvert et al. 2009 26.5 Fauvert et al. 2009 ++
11 c.1256delC p.Pro419Leufs P Pro402Leufs Taillandier et al. 2000 perinatal c.[1256delC];[?]         na
11 c.1258G>A p.Gly420Ser P Gly403Ser Glaser et al. 2004 perinatal c.[1258G>A];[1258G>A]

0

Makita et al. 2012

40

Makita et al. 2012 ++
11 c.1259G>C p.Gly420Ala P Gly403Ala Fauvert et al. 2009 childhood c.[571G>A];[1259G>C] 4.2 Fauvert et al. 2009 19.7 Fauvert et al. 2009 ++
11 c.1259G>A p.Gly420Asp   Gly403Asp Versailles lab Feb. 2019 childhood c.[1259G>A];[=]         ++
11 c.1265A>G p.Lys422Arg   Lys405Arg Versailles lab April 2018 adult c.[1265A>G];[=]         +
11 c.1268T>C p.Val423Ala P Val406Ala Taillandier et al. 2001 perinatal c.[346G>A];[1268T>C] 15.7 Numa et al. 2008     +
11 c.1270G>A p.Val424Met P Val407Met Versailles lab jan. 2007 adult c.[1270G>A];[1270G>A]         +
11 c.1271T>C p.Val424Ala P Val407Ala Zhang et al. 2012 adult c.[1271T>C];[1271T>C]         +
11 c.1276G>T p.Gly426Cys P Gly409Cys

Mochizuki et al. 2000

infantile

c.[670A>G];[1276G>T]

18.5 Michigami et al. 2005     ++
11 c.1276G>A p.Gly426Ser P Gly409Ser

Versailles lab Apr 2011

infantile

c.[1276G>A];[1276G>A]

10

Al-Shawafi et al. 2016 50 Al-Shawafi et al. 2016 ++
11 c.1277G>A p.Gly426Asp P Gly409Asp Mumm et al. 2002 childhood c.[571G>A];[1277G>A] 0 Al-Shawafi et al. 2016 60 Al-Shawafi et al. 2016 ++
11 c.1282C>T p.Arg428* P Arg411Ter Taillandier et al. 1999 perinatal c.[1282C>T];[1282C>T]         na
11 c.1283G>C p.Arg428Pro P Arg411Pro Spentchian et al. 2006 perinatal c.[997+2T>A];[1283G>C]         ++
11 c.1283G>A p.Arg428Gln   Arg411Gln Versailles lab Jul. 2010 prenatal benign c.[1283G>A];[=]         ++
11 c.1283G>T p.Arg428Leu   Arg411Leu Plendl et al. 2011 adult c.[1283G>T];[?]         ++
11 c.1285G>A p.Glu429Lys P Glu412Lys Versailles lab Jul. 2006 odonto. c.[1285G>A];[?] 1.3 Fauvert et al. 2009 31.0 Fauvert et al. 2009 ++
11 c.1289A>G p.Asn430Ser P Asn413Ser Whyte et al. 2015 infantile c.[571G>A];[1289A>G] 0 Komaru et al. 2016

58

Komaru et al. 2016 ++
11 c.1292T>A p.Val431Asp LP Val414Asp Esmel-Vilomara et al. 2019 prenatal benign c.[1292T>A];[=]         +
11 c.1292T>C p.Val431Ala P Val414Ala Taillandier et al. 2015 odonto. c.[1292T>C];[=]         +
11 c.1306T>C p.Tyr436His P Tyr419His Henthorn et al. 1992 childhood c.[98C>T];[1306T>C]         ++
11 c.1307A>G p.Tyr436Cys P Tyr419Cys Taketani et al. 2013 infantile c.[1307A>G];[1559delT]         ++
11 c.1307A>C p.Tyr436Ser   Tyr419Ser Nielson et al. 2012 asymptomatic*, low BMD c.[1307A>C];[=]         ++
                         
12 c.1313A>T p.His438Leu P His421Leu Versailles lab oct. 2009 infantile c[.1313A>T].[1313A>T]         ++
12 c.1318_1320 delAAC p.Asn440del P Asn423del Martins et al. 2013 odonto. c.[454C>T];[1318_1320delAAC]         na
12 c.1323C>A p.Tyr441* P Tyr424* Hofmann et al. 2013 perinatal c.[667C>T];[1323C>A] 1.0 Hofmann et al. 2013 58.3 Hofmann et al. 2013 na
12 c.1327G>A p.Ala443Thr   Ala426Thr Garcia-Fontana et al. 2019 Adult c.[1327G>A];[=]         ++
12 c.1328C>T p.Ala443Val P Ala426Val

Fauvert et al. 2009

adult

c.[1328C>T];[=]

1.4 Fauvert et al. 2009 53.1 Fauvert et al. 2009 ++
12 c.1328C>A p.Ala443Glu P Ala426Glu Khandwala et al. 2006 adult c.[1328C>A];[=]         ++
12 c.1333T>C p.Ser445Pro P Ser428Pro Mornet et al. 1998 infantile c.[1333T>C];[?] 2.1 Zurutuza et al. 1999 35.1 Fauvert et al. 2009 +
12 c.1336G>A p.Ala446Thr P Ala429Thr Versailles lab Jan 2013 perinatal c.[1336G>A];[1336G>A]         ++
12 c.1349G>A p.Arg450His P Arg433His Taillandier et al. 2000 odonto. c.[1217A>G];[1349G>A]         +
12 c.1348C>T p.Arg450Cys P Arg433Cys Mornet et al. 1998 infantile c.[1348C>T];[1348C>T] 4.0 Zurutuza et al. 1999     +
12 c.1354G>A p.Glu452Lys P Glu435Lys Spentchian et al. 2003 perinatal c.[331G>A];[1354G>A] 1.4 Fauvert et al. 2009 27.5 Fauvert et al. 2009 ++
12 c.1361A>G p.His454Arg P His437Arg Versailles lab oct. 2003 childhood c.[571G>A];[1361A>G]         ++
12 c.1363G>A p.Gly455Ser P Gly438Ser Draguet et al. 2004 adult c.[1363G>A];[1471G>A] 71.0 Brun-Heath et al. 2007     ++
12 c.1364G>A p.Gly455Asp P Gly438Asp Versailles lab jan. 2007 perinatal c.[1364G>A];[1364G>A]         ++
12 c.1366G>T p.Gly456Trp P Gly439Trp Versailles lab oct. 2003 childhood c.[1366G>T];[?] 0.8 Fauvert et al. 2009 14.5 Fauvert et al. 2009 ++
12 c.1366G>A p.Gly456Arg   Gly439Arg Ozono et al. 1996 infantile c.[1366G>A];[?] 1.5 Fauvert et al. 2009 50.5 Fauvert et al. 2009 ++
12 c.1367G>A p.Gly456Glu   Gly439Glu Versailles lab. Dec 2018 Odonto c.[1367G>A];[=]         ++
12 c.1372G>A p.Asp458Asn   Asp441Asn Versailles lab Dec 2011 adult c.[571G>A];[372G>A]         ++
12 c.1373A>G p.Asp458Gly   Asp441Gly Plendl et al. 2011 infantile c.[571G>A];[1373A>G]         ++
12 c.1375G>A p.Val459Met P Val442Met

Taillandier et al. 2000

Whyte et al. 2016

infantile

infantile

c.[152C>T];[1375G>A]

c.[252G>C];[1375G>A]

        ++
12 c.1375G>T p.Val459Leu P Val442Leu Versailles lab oct. 2004 perinatal c.[1354G>A];[1375G>T] 0 Fauvert et al. 2009 41.1 Fauvert et al. 2009 ++
12 c.1376T>C p.Val459Ala   Val442Ala Xu et al. 2018 adult c.[1376T>C];[=]         ++
12 c.1381G>A p.Val461Ile LP Val444Ile Nielson et al. 2012 asymptomatic*, low BMD c.[1381G>A];[?]         +
12 c.1397C>T p.Pro466Leu P Pro449Leu Versailles lab oct. 2003 perinatal c.[1397C>T];[?]         +
12 c.1400T>C p.Met467Thr P Met450Thr Versailles lab oct. 2004 infantile c.[919C>T];[1400T>C]         +
12 c.1402G>A p.Ala468Thr P Ala451Thr Spentchian et al. 2003 perinatal c.[1402G>A];[1402G>A]         ++
12 c.1403C>T p.Ala468Val   Ala451Val Taillandier et al. 2017 adult c.[1403C>T];[=]         ++
12 c.1412_1429del18 p.Leu471_Glu476del   Leu454_Glu459del Plendl et al. 2011 adult c.[1412_1429del18];[?]         na
12 c.1414C>T p.His472Tyr   His455Tyr V. Buzzi, P. La Verde, Milan, Italy perinatal c.[299C>T];[1414C>T]         ++
12 c.1417G>A p.Gly473Ser P Gly456Ser

Mornet et al. 1998

Martins et al. 2019

perinatal

adult

c.[119C>T];[1417C>T]

c.[1417C>T];[1460C>T]

        ++
12 c.1418G>A p.Gly473Asp   Gly456Asp Nakamura-Utsunomiya et al. 2010 perinatal c.[1418G>A];[1559delT]         ++
12 c.1418_1438dup p.Gly473_Tyr479dup LP Gly456_Tyr62dup Versailles lab Dec. 2019 asymptomatic c.[1418_1438dup];[=]         na
12 c.1426G>A p.Glu476Lys P Glu459Lys Taillandier et al. 1999 perinatal c.[331G>A];[1426G>A]         ++
12 c.1426G>T p.Glu476*   Glu459* Clinvar (Counsyl) infantile not provided         ++
12 c.1427A>G p.Glu476Gly P Glu459Gly Mornet et al. 2001 perinatal c.[1427A>G];[1427A>G]         ++
12 c.1427A>C p.Glu476Ala P Glu459Ala Versailles lab March 2009 adult c.[1427A>C];[?] 0.4 Fauvert et al. 2009 39.3 Fauvert et al. 2009 ++
12 c.1433A>T p.Asn478Ile P Asn461Ile Taillandier et al. 2000 childhood c.[1433A>T];[=] 1.1 Lia-Baldini et al. 2001 38.2 Lia-Baldini et al. 2001 ++
12 c.1444C>A p.His482Asn P His465Asn Nielson et al. 2012 asymptomatic*, low BMD c.[1444C>A];[=]         ++
12 c.1444_1445dupC p.His482Profs   His465Profs Brun-Heath et al. 2005 perinatal c.[1444_1445insC];[1001G>A]         na
12 c.1447G>A p.Val483Met   Val466Met Research center for medical genetics, Moscow, Aug. 2016 childhood c.[1447G>A];[?]         +
12 c.1460C>T p.Ala487Val P Ala470Val

Taillandier et al. 2015

Martins et al. 2019

perinatal

adult

c.[1460C>T];[.984_986delCTT]

c.[1417C>T];[1460C>T]

        ++
12 c.1466G>C p.Cys489Ser P Cys472Ser Taillandier et al. 2000 perinatal c.[997+2T>A];[1466G>C] 9.4 Taillandier et al. 2000     ++
12 c.1468A>T p.Ile490Phe P Ile473Phe Lia-Baldini et al. 2001 adult c.[1468A>T];[?] 37.1 Lia-Baldini et al. 2001 77.4 Lia-Baldini et al. 2001 +
12 c.1471G>A p.Gly491Arg P Gly474Arg Mornet et al. 1998 perinatal c.[385G>A];[1471G>A]         ++
12 c.1474delG p.Ala492Profs P Ala475Profs

Brun-Heath et al. 2005
Galeano-Valle et al. 2019

odonto

adult

c.[1474delG];[407G>A]

c.[1474delG];[=]

        na
12 c.1479C>A p.Asn493Lys P Asn476Lys Porntaveetus et al. 2017 infantile c.[1460C>T];[1479C>A]         -
12 c.1483G>A p.Gly495Ser   Gly478Ser Michigami et al.2019 infantile c.[1483G>A];[1483G>A]         -
12 c.1489T>A p.Cys497Ser   Cys480Ser Xu et al. 2018 adult c.[1489T>A];[=]         ++
12 c.1530_1549del20 p.Leu512Profs   Leu495Profs Clinvar (Counsyl) infantile not provided         na
12 c.1540G>A p.Ala514Thr LP Ala497Thr Tenorio et al. 2017 infantile c.[1540G>A];[407G>A]         +
12 c.1553_1569del17 p.Tyr518Phefs   Tyr501Phefs Versailles lab nov. 2009 perinatal c.[1553_1569del];[881A>C]         na
12 c.1554C>A p.Tyr518*   Tyr501* Dr S. Monnot, Necker Hospital, Paris, France, Feb. 2019 perinatal c.[1554C>A];[1554C>A]         na
12 c.1559delT p.Leu520Argfs P Leu503Argfs

Orimo et al. 1994

Katsuyuki et al. 2019

Michigami et al.2019

Michigami et al.2019

Michigami et al.2019

Michigami et al.2019

Michigami et al.2019

Michigami et al.2019

Michigami et al.2019

infantile

childhood

perinatal severe

perinatal benign

odonto

odonto

odonto

odonto

odonto

c.[892G>A];[1559delT]

c.[1183A>G];[1559delT]

c.[1559delT];[1559delT]

c.[572A>G];[1559delT]

c.[704A>T];[1559delT]

c.[407G>A];[1559delT]

c.[979T>C];[1559delT]

c.[572A>G];[1559delT]

p.[Pro409Ala];c.[1559delT]

28 Komaru et al. 2005     na
12 c.*124_126delinsAG   VUS   Versailles lab Sept 2019 adult c.[124_126delinsAG]       na


Large deletions/duplications

Due to the incertainty of borders, all large deletions/duplications submitted to the database will be included. However, each type will be counted only once.

deletion of exon 1       Versailles lab July 2012 perinatal homozygote         na

3kb deletion in IVS1

      Versailles lab Oct. 2016 infantile

compound heterozygote with
deletion exon 1 - IVS1 - exon 2

        na
deletion exon 1 - IVS1 - exon 2       Versailles lab May 2016 infantile compound heterozygote with 3kb deletion in IVS1         na
deletion of exon 2       Versailles lab July 2013 perinatal homozygote         na
deletion of exon 2       H Mateus, Alexion Pharmaceuticals, Colombia infantile compound heterozygote with c.[382G>A]         na
deletion of exon 2       Versailles lab Nov. 2018 adult heterozygote         na
del IVS3       Whyte et al. 2015 odonto. heterozygote         na
deletion exons 2-6       Dr I. Rau , Institut für Humangenetik, Hamburg, Germany adult heterozygote         na
duplication of exons 2-6   P   Hacihamdioglu et al. 2018 perinatal homozygote         na
deletion of exons 3-5   P   Spentchian et al. 2006 perinatal homozygote         na
indel in exon 5       Whyte et al. 2015 odonto. heterozygote         na
deletion of exon 5       Versailles lab April 2018 adult heterozygote         na
deletion of exon 9 (3' part)       Versailles lab Dec. 2015 prenat. benign compound heterozygote with c.407G>A         na
deletion of exon 12 (3' part)   P   Spentchian et al. 2006 infantile compound heterozygote
with c.542C>T
        na

* Phenotype "asymptomatic": repeatedly low serum alkaline phosphatase, no hypophosphatasia clinical symptom

 

Statistics

Type of mutation Number of mutations %
Missense 291 71.1
Small deletions 41 10.0
Splicing 24 5.8
Nonsense 18 4.4
Small insertions 15 3.7
Large del/dup 12 2.9
Ins/Del 6 1.5
Regulatory 2 0.5
Total 409 100

 

 

 

 

Legend to database items
  • Nomenclature : see the nomenclature section below.
  • Reference : reference of the publication reporting the mutation.
  • Pathogenicity: : classification of the variant according to Richards et al. (2015) and Karbassi et al. (2015). The classification give a score of pathogenicity : B benign; LB likely benign; VUS variant of unknown significance; LP likely pathogenic; P pathogenic
  • Clinical form : clinical form of the patient in whom the mutation was detected for the first time.
  • Genotype : genotype of the patient in whom the mutation was detected for the first time.
  • ? : uncharacterized allele (only one detected mutation without molecular, pedigree, or in silico evidence of dominant transmission).
  • N : normal allele (dominant mutation on the other chromosome, evidenced by molecular, pedigree, or in silico data.
  • %WT : residual activity of the mutant protein. Alkaline phosphatase activity of cells transfected with mutant cDNAs, expressed in percentage of the activity found in cells transfected with wild type (WT) cDNA.
  • % 50/50 : dominant negative effect of the mutation. Alkaline phosphatase activity of cells co-transfected with equal quantities of wild type and mutant cDNAs, expressed in percentage of the activity found in cells transfected with wild type (WT) cDNA. For mutations producing no residual activity, the value is expected to be 50% if there is no dominant negative effect, and <50% if there is a dominant negative effect (Lia-Baldini et al. 2001).
  • unp. : unpublished.
  • Conservation : conservation of the affected amino acid among 58 mammalian TNSALP according to Silvent et al. (2014). ++ conserved residue ; + conservative changes only, - residue not conserved, na not applicable.

Nomenclature

  • Nucleotides numbering is given according to Weiss et al. 1988, the Nomenclature Working Group (S.E. Antonarakis and the Nomenclature Working Group, Hum. Mut. 11:1-3, 1998) and the HGVS recommendations: the first nucleotide (+1) corresponds to the A of the ATG initiation codon. The reference cDNA sequence is NM_000478.5
  • Amino acids numbering is given according to both the standardized and the non-standardized nomenclatures.
    The standardized nomenclature follows the HGVS recommendations: the first codon is the ATG initiation codon.
    The non-standardized nomenclature was used in publications before 2008-2009 : this nomenclature takes into account of a 17-residues signal peptide, i.e. the ATG initiation codon is numbered as residue minus (-)17 (Weiss et al. 1988). The reference cDNA sequence is NM_000478.5
  • p: protein numbering; c: nucleotide numbering of the coding sequence.

References:

Contact database: