The Tissue Nonspecific Alkaline Phosphatase
Gene Mutations Database

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 : May 06, 2015
Total number of mutations described : 300



Hypophosphatasia (MIM 146300, 241500, 241510)

Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization and deficiency of serum and bone alkaline phosphatase activity. For severe forms, the prevalence of the disease has been estimated to 1/300,000 in Europe and 1/100 000 in Canada. 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, localized on chromosome 1p36-34 (Greenberg et al. 1990), consists of 12 exons distributed over 50 kb (Weiss et al. 1988) and is subject to very strong allelic heterogeneity. To date, at least 300 distinct mutations are known (see the list of mutations below and the list of polymorphisms). The patients examined mostly consisted of European, North-American, Australian and Japanese individuals.

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

Exon Base change
Amino acid change (standardized nomenclature)
Reference Clinical form in patient Genotype of patient % WT ref. Conservation
1 c.-195C>T   Taillandier et al. 2000 perinatal c.-195C>T/p.C201Y     na
2 c.3G>A p.M1I Mentrup et al. 2011 adult p.M1I/? 1.0 22 ++
2 c.17T>A p.L6X Taillandier et al. 2000 childhood p.L6X/?     na
2 c.41T>C p.L14P Versailles lab Jul 2010 adult p.L14P/p.E191K     +
2 c.43_46delACTA p.N16PfsX2 Versailles lab March 2011 infantile c.43_46delACTA/p.R220Q     na
2 c.50C> T p.S17F Mornet et al. 1998 infantile p.S17F/p.G75S 19.0 1 +
IVS2 c.62-1G>C   Versailles lab March 2013 perinatal c.62-1G>C/c.62-1G>C     na
3 c.69_74delGAAAGA   Versailles lab May 2012 perinatal c.69_74delGAAAGA/p.N49I     na
3 c.82T>G p.Y28D Yang et al. 2013 odonto p.Y28D/p.Y388H 0 26 ++
3 c.83A>G p.Y28C Taillandier et al. 2001 infantile p.Y28C/p.R136H 7.2 2 ++
3 c.88C>T p.R30X Versailles lab Dec 2010 perinatal p.R30X/p.G129R     na
3 c.94C>T p.Q32X Versailles lab. Apr 2011 perinatal p.Q32X/c.648+1G>A     na
3 c.98C>T p.A33V Henthorn et al. 1992 childhood p.A33V/p.Y436H     +
3 c.106A>C p.T36P Versailles lab Nov 2008 perinatal p.T36P/p.T36P     ++
3 c.110T>C p.L37P Versailles lab oct. 2003 perinatal p.L37P/p.L37P     ++
3 c.119C>T p.A40V Mornet et al. 1998 perinatal p.A40V/p.G473S 2.3 1 +
3 c.129delT p.Q44RfsX23 Whyte et al. 2015 childhood c.129delT/p.Y436C     na
3 c.130C>T p.Q44X Mornet E, unpublished perinatal p.Q44X/c.662insG     na
3 c.146A>T p.N49I Versailles lab May 2012 perinatal p.N49I/c.69_74delGAAAGA     +
3 c.151G>T p.A51S Mumm et al. 2002 infantile p.A51S/p.T134H     ++
3 c.152C>T p.A51V Taillandier et al. 2001 infantile p.A51V/p.V459M     ++
3 c.180T>C p.D60E Whyte et al. 2015 childhood p.D60E/N     ++
IVS3 c.182-2A>C   Whyte et al. 2015 childhood c.182-2A>C     na
4 c.184A>T p.M62L Taillandier et al. 1999 infantile p.M62L/c.1172delC 27.4 1 ++
4 c.184A>G p.M62V Spentchian et al. 2003 infantile p.M62V/p.M62V     ++
4 c.186G>C p.M62I Taillandier et al.2005 childhood p.M62I/p.E191K 0 16 ++
4 c.187G>C p.G63R Spentchian et al. 2003 infantile p.G63R/p.G63R     ++
4 c.187_205del19 p.G63LfsX53 Versailles lab Jan 2010 adult c.187_205del/N     na
4 c.188_205dup18 p.G63_T68dup Guanabens et al. 2013 adult c.188_205dup18/N     na
4 c.188G>T p.G63V Lia-Baldini et al. 2001 infantile p.G63V/N 0.8 3 ++
4 c.203C>T p.T68M Orimo et al. 2002 childhood p.T68M/p.A177T 5.2 4 ++
4 c.211C>T p.R71C Henthorn et al. 1992 infantile p.R71C/p.D294A 0 17 ++
4 c.211C>A p.R71S Orimo et al. 2002 childhood p.R71S/? 2.9 4 ++
4 c.212G>C p.R71P Henthorn et al. 1992 perinatal p.R71P/p.Q207P     ++
4 c.212G>A p.R71H Taillandier et al. 2001 perinatal p.A40V/p.R71H 1.0 20 ++
4 c.215T>C p.I72T Versailles lab oct. 2004 odonto p.I72T/N 5.1 20 ++
4 c.216A>G p.I72V Versailles lab dec. 2014 infantile p.I72V/p.I72V     ++
4 c.217_219delCTC p.L73del Versailles lab aug. 2013 asymptomatic* p.F73del/N     na
4 c.223G>A p.G75S Mornet et al. 1998 infantile p.S17F/p.G75S 3.5 1 ++
4 c.227A>G p.Q76R Mornet et al. 2001 infantile p.Q76R/p.T134N     ++
4 c.242delC p.P81LfsX41 Versailles lab Jul 2009 perinatal c.240delC/c.240delC     na
4 c.247G>T p.E83X Versailles lab Apr 2011 infantile p.E83X/p.E83X     na
4 c.251A>T p.E84V Wei et al. 2010 odonto p.E84V/N     +
4 c.262G>A p.E88K Mohn et al. 2011 infantile p.E88K/p.P307L     ++
4 c.277C>T p.P93S Peach et al. 2007 prenat. benign p.P93S/p.T134H     ++
IVS4 c.297+3G>T   Versailles lab. Jan 2011 infantile c.297+3G>T/p.T100M     na
IVS4 c.298-2A>G   Taillandier et al. 2000 perinatal c.298-2A>G/c.997+3A>C     na
IVS4 c.298-1G>A   Zhang et al. 2012 adult c.298-1G>A/c.298-1G>A     na
5 c.299C>T p.T100M Mornet et al. 2001 infantile p.T100M/p.E191K 1.3 20 ++
5 c.301T>G p.Y101D Versailles lab. Feb 2012 Odonto p.Y101D/N     ++
5 c.303_311del p.N102_N104del Versailles lab Jul 2007 perinatal c.303_311del/p.G491R     na
5 c.318G>C p.Q106H Balasubramaniam et al. 2010 infantile p.Q106H/p.Q106H     ++
5 c.323C>T p.P108L Herasse et al. 2003 odonto p.P108L/N 0.4 unp. ++
5 c.331G>A p.A111T Goseki-Sone et al. 1998 odonto p.A111T/? 2.0 20 ++
5 c.334G>A p.G112S Witters et al. 2004 infantile p.G112S/p.R391C     ++
5 c.334G>C p.G112R Whyte et al. 2015 odonto. p.G112R/N     ++
5 c.335_340dupGCACCG p.G112_113dup Wenkert et al. 2011 prenatal benign G95_96dup/p.E191K     na
5 c.340G>A p.A114T Mumm et al. 2001 infantile p.A114T/p.D294A     ++
5 c.341C>G p.A114G Draguet et al. 2004 perinatal

p.A114G+c.348_349insACCGTC
/p.G326R

    ++
5 c.346G>T p.A116S Versailles lab Jul 2007 adult p.A116S/p.N417S     ++
5 c.346G>A p.A116T Hu et al. 2000 adult p.A116T/N 0.8 3 ++
5 c.348_349insACCGTC p.A116_Y117insTV Draguet et al. 2004 perinatal p.A116G+c.348_349insACCGTC
/p.G326R
    na
5 c.343_348dupACCGCC p.T115_A116dup Versailles lab March 2009 odonto c.348_349insACCGCC     na
5 c.350A>G p.Y117C Whyte et al. 2009 childhood p.Y117C/p.T134H     +
5 c.358G>A p.G120R Mornet et al. 1998 perinatal p.G120R/c.648+1G>A     ++
5 c.368C>A p.A123D Spentchian et al. 2006 perinatal p.A123D/p.S266_H267del     +
5 c.382G>A p.V128M Mumm et al. 2002 perinatal p.V128M/p.R223W     +
5 c.385G>A p.G129R Mornet et al. 1998 perinatal p.G129R/p.G491R     ++
5 c.388_391delGTAA p.V130AfsX34 Spentchian et al. 2003 perinatal p.E311K/c.388_391delGTAA     na
5 c.389delT p.V130EfsX35 Spentchian et al. 2003 perinatal c.389delT/c.389delT     na
5 c.392delG p.S131TfsX34 Mumm et al. 2002 perinat/infant c.392delG/p.A348T     na
5 c.394G>A p.A132T Versailles lab Jul 2006 adult p.A132T/p.E191K     ++
5 c.395C>T p.A132V Watanabe et al. 2001 adult p.A132V/? 16.9 14 ++
5 c.400_401AC>CA p.T134H Mumm et al. 2002 perinatal p.T134H/p.F327del     +
5 c.401C>A p.T134N Taillandier et al. 2000 perinatal p.T134N/p.T134N 20.5 5 +
5 c.406C>T p.R136C Versailles lab oct. 2003 odonto p.R136C/p.R136H     ++
5 c.407G>A p.R136H Taillandier et al. 1999 infantile p.R136H/p.G162V 33.4 1 ++
5 c.407G>T p.R136L Yang et al. 2013 childhood p.R136L/p.T389N 35 26 ++
5 c.422C>A p.T141N Whyte et al. 2015 childhood p.141N/p.H210R     ++
5 c.422C>T p.T141I Versailles lab Jul 2008 infantile p.T141I/p.P307L     ++
5 c.427delC p.Q143RfsX22 Whyte et al. 2015 childhood c.427delC/p.H482N     na
5 c.436G>A p.E146K Nielson et al. 2012 asymptomatic, low BMD p.E146K/N     ++
5 c.442A>G p.T148A Michigami et al. 2005 perinatal p.T148A/?     ++
5 c.443C>T p.T148I Spentchian et al. 2003 infantile p.T148I/p.G162S     ++
5 c.454C>T p.R152C Versailles lab Nov. 2009 adult p.R152C/p.R184W     +
5 c.457T>C p.W153R Wenkert et al. 2011 prenatal benign p.I412V/p.W153R     ++
5 c.472+1G>A   Liu et al. 2010 odonto c.472+1G>A/p.V374M     na
6 c.480delT   Versailles lab. Jan. 2008 perinatal c.480delT/p.R223W     na
6 c.484G>A p.G162S Spentchian et al. 2003 infantile p.T148I/p.G162S     ++
6 c.485G>T p.G162V Taillandier et al. 1999 infantile p.R136H/p.G162V 1.3 1 ++
6 c.491T>G p.V164G Versailles lab March 2009 infantile p.V164G/p.D294A     ++
6 c.500C>T p.T167M Versailles lab Oct. 2003 infantile p.T167M/p.E191K 0   +
6 c.508A>G p.N170D Mornet et al. 1998 perinatal p.N170D/p.N170D 0 13 +
6 c.511C>T p.H171Y Taillandier et al. 1999 infantile p.H171Y/p.E191K 2.1 1 ++
6 c.512A>G p.H171R Mornet E, unpublished adult p.H171R/p.E191K     ++
6 c.526G>A p.A176T Taillandier et al. 2000 childhood p.A176T/p.R246S 45.4 5 ++
6 c.529G>A p.A177T Goseki-Sone et al. 1998 adult p.A177T/p.F327L 83.8 4 +
6 c.535G>A p.A179T Weiss et al. 1988 perinatal p.A179T/p.A179T 18 6 ++
6 c.542C>T p.S181L Lia-Baldini et al. 2001 infantile p.S181L/del(ex12) 1.3 3 ++
6 c.544delG p.A182LfsX16 Taillandier et al. 1999 perinatal p.G249V/c.544delG     na
6 c.547G>C p.D183H Versailles lab Nov 2008 infantile p.D183H/p.D294A     +
6 c.550C>T p.R184W Mornet et al. 1998 perinatal p.R184W/p.W270X 0.6 3 ++
6 c.551G>A p.R184Q Versailles lab. Nov. 2013 Infantile p.R184Q/p.T68M     ++
6 c.567C>A p.D189E Spentchian et al. 2003 perinatal p.D189E/p.D189E     ++
6 c.568_570delAAC p.N190del Michigami et al. 2005 perinatal c.1559delT/p.N190del     na
6 c.571G>A p.E191K Henthorn et al. 1992 infantile p.E191K/p.D378V 88.0 1 ++
6 c.572A>G p.E191G Goseki-Sone et al. 1998 odonto p.E191G/c.1559delT     ++
6 c.575T>C p.M192T Versailles lab Jul 2007 infantile p.M192T/p.E311K     ++
6 c.577C>G p.P193A Mumm et al. 2002 adult p.A114T/p.P193A     +
6 c.599G>A p.G200D Versailles lab April 2014 adult p.G200D/N     ++
6 c.602G>A p.C201Y Taillandier et al. 1999 perinatal c.-195C>T/p.C201Y 0 23 ++
6 c.609C>G p.D203E Versailles lab oct. 2004 perinatal p.D203E/p.D203E     ++
6 c.614C>T p.A205V Versailles lab aug. 2013 asymptomatic* p.A205V/N     +
6 c.620A>C p.Q207P Henthorn et al. 1992 perinatal p.R71P/p.Q207P     ++
6 c.622C>T p.L208F Versailles lab april 2009 perinatal p.L208F/p.L208F     ++
6 c.629A>G p.H210R Whyte et al. 2015 childhood p.H210R/p.T141N     +
6 c.630_637dupTAACATCA p.R213IfsX8 Versailles lab June 2011 perinatal c.630_637dupTAACATCA/c.792G>A     na
6 c.631A>G p.N211D Taillandier et al. 2001 infantile p.A116T/p.N211D     ++
6 c.634A>T p.I212F Souka et al. 2002 perinatal p.I212F/p.E354D     +
6 c.644T>C p.I215T Versailles lab. march 2011 infantile p.I215T/p.S181L     ++
IVS6 c.648+1G>T   Brun-Heath et al. 2005 perinatal c.648+1G>T/p.D294A     na
IVS6 c.648+1G>A   Mornet et al. 1998 perinatal p.G120R/c.648+1G>A     na
IVS6 c.648+2_3insT   Versailles lab jan 2013 perinatal c.648+2_3insT/p.A399V     na
IVS6 c.649-1_3delinsAA   Versailles lab Jul 2006 perinatal c.649-1_3delinsAA/c.649-1_3delinsAA     na
7 c.650delTinsCTAA p.217delVinsAK Chang et al. 2011 perinatal c.650delTinsCTAA/p.F327del     na
7 c.653T>C p.I218T

Utsch et al., 2009

perinatal p.I218T/p.R391C 3.7 19 ++
7 c.655A>G p.M219V Yang et al. 2013 odonto p.M219V/p.A111T 75 26 +
7 c.658G>A p.G220R Versailles lab Dec 2011 perinatal p.G220R/p.G220R     ++
7 c.659G>T p.G220V Taillandier et al. 2001 odonto p.E191K/p.G220V     ++
7 c.659G>C p.G220A Spentchian et al. 2003 perinatal p.G220A/p.G220A     ++
7 c.661G>C p.G221R Versailles lab March 2009 perinatal p.G221R/?     ++
7 c.662_663insG p.G222WfsX10 Mornet E, unpublished perinatal p.Q44X/c.662_663insG     na
7 c.662delG p.G221VfsX56 Spentchian et al. 2003 perinatal p.R272L/c.662delG     na
7 c.662G>T p.G221V Versailles lab oct. 2004 perinatal p.G221V/p.M355T     ++
7 c.667C>T p.R223W Mornet et al. 1998 perinatal p.R223W/? 2.8 3 ++
7 c.668G>A p.R223Q Mumm et al. 2002 perinatal p.R223Q/deletion 2.9 25 ++
7 c.670A>G p.K224E Mochizuki et al. 2000 infantile p.K224E/p.G426C 43 15 ++
7 c.677T>C p.M226T Baumgartner-Sigl et al. 2007 infantile p.M226T/p.T371I     ++
7 c.704A>G p.E235G Taillandier et al. 2001 adult p.E235G/p.A399S 3.6 7 ++
7 c.738G>T p.R246S Taillandier et al. 2000 childhood p.A176T/p.R246S 4.4 5 ++
7 c.746G>T p.G249V Fedde et al. 1996 perinatal p.G249V/N 34.5 3 +
7 c.791A>G p.K264R Brun-Heath et al. 2007 perinatal p.K264R/p.D378V     +
7 c.792G>A p.K264K Versailles lab june 2011 perinatal p.K264K/c.630_637dupTAACATCA     na
8 c.797_802del p.S266_H267del Spentchian et al. 2006 perinatal p.A123D/p.S266_p.H267del     na
8 c.809G>A p.W270X Mornet et al. 1998 perinatal p.R184W/p.W270X 1.2 1 na
8 c.814C>T p.R272C Spentchian et al. 2006 perinatal p.R272C/p.T134H     ++
8 c.814delC p.R272AfsX5 Versailles lab June 2011 perinatal c.814delT/p.H381R     na
8 c.815G>T p.R272L Spentchian et al. 2003 perinatal p.R272L/c.662delG     ++
8 c.815G>A p.R272H Brun-Heath et al. 2005 infantile p.R272H/p.R272H 6.8 16 ++
8 c.818C>T p.T273M Nielson et al. 2012 asymptomatic, low BMD p.T273M/N     +
8 c.824T>C p.L275P Orimo et al. 2002 childhood p.L275P/p.A177T 3.3 4 ++
8 c.853_854insGATC p.Y285X Michigami et al. 2005 perinatal c1559delT/p.Y285X     na
IVS8 c.862+5G>A   Taillandier et al. 1999 infantile c.862+5G>A/c.862+5G>A     na
9 c.865C>T p.L289F Sugimoto et al. 1998 infantile p.L289F/? 50 8 ++
9 c.871G>A p.E291K Mornet et al. 1998 infantile p.E191K/p.E291K 8.3 1 ++
9 c.871G>T p.E291X Taillandier et al. 2000 perinatal p.A111T/p.E291X     na
9 c.871G>C p.E291Q Versailles lab Jun 2010 perinatal p.E291Q/p.E291Q     ++
9 c.874C>A p.P292T Brun-Heath et al. 2005 infantile p.P292T/p.A33V 4.0 16 ++
9 c.875_881delCAGGGGAinsT   Belachew et al. 2013 perinatal c.875_881delCAGGGGAinsT/c.1559delT     na
9 c.876_881delAGGGGA p.G293_D294del Spentchian et al. 2003 perinatal p.G293_p.D294del/c.962delG     na
9 c.880G>T p.D294Y Taillandier et al. 2001 infantile p.A176T/p.D294Y     ++
9 c.881A>C p.D294A Henthorn et al. 1992 infantile p.R71C/p.D294A 35 17 ++
9 c.883A>G p.M295V Mornet et al. 2001 childhood p.E191K/p.M295V     +
9 c.884T>C p.M295T Brun-Heath et al. 2005 perinatal p.M295T/p.R223W 8.5 16 +
9 c.885G>A p.M295I Michigami et al. 2005 perinatal p.M295I/c.1559delT     +
9 c.886C>T p.Q296X Plendl et al. 2011 adult p.Q296X/?     na
9 c.889T>G p.Y297D Brun-Heath et al. 2005 childhood p.R136H/p.Y297D 1.3 16 ++
9 c.889T>C p.Y297H Bertola et al. 2009 perinatal p.Y297H/c.648+1G>A     ++
9 c.891C>A p.Y297X Balasubramaniam et al. 2010 Infantile p.Y297X/p.G491R     na
9 c.892G>A p.E298K Orimo et al. 1994 infantile p.E298K/c.1559delT     ++
9 c.896T>C p.L299P Versailles lab oct. 2003 infantile p.L299P/p.L299P 9.7 15 ++
9 c.917A>T p.D306V Taillandier et al. 1999 infantile p.D306V/p.D306V 0 12 ++
9 c.919C>T p.P307S Versailles lab oct. 2004 infantile p.P307S/p.M467T     ++
9 c.920C>T p.P307L Versailles lab Jul. 2006 childhood p.P307L/p.S181L     ++
9 c.928_929delTC p.S310RfsX27 Brun-Heath et al. 2005 perinatal T394A/c.928_929delTC     na
9 c.931G>A p.E311K Spentchian et al. 2003 perinatal p.E311K/c.388_391delGTAA     ++
9 c.952C>T p.Q318X Versailles lab Dec 2011 perinatal p.Q318X/p.D406N     na
9 c.963delG p.K322RfsX44 Spentchian et al. 2003 perinatal p.G293_D294del/c.963delG     na
9 c.969C>G p.N323K Versailles lab oct. 2009 childhood p.N323K/c.648+1G>A     ++
9 c.976G>C p.G326R Litmanovitz et al. 2002 perinatal p.G326R/p.E291K     ++
9 c.977G>T p.G326V Versailles lab Jul 2008 perinatal p.G326V/pG326V     ++
9 c.984_986delCTT p.F328del Orimo et al. 1997 infantile p.F328del/c.1559delT ~10 15 na
9 c.979T>G p.F327C Mornet et al. 2001 perinatal p.T134N/p.F327C     ++
9 c.979_980TT>GG p.F327G Taillandier et al. 2001 adult p.E191K/p.F327G     ++
9 c.979T>C p.F327L Ozono et al. 1996 infantile p.F327L/p.G456R 72 9 ++
9 c.982T>C p.F328L Michigami et al. 2005 perinatal non-lethal p.F328L/p.T100M ~10 15 ++
9 c.997+1G>T   Liu et al. 2010 odonto c.997+1G>T/p.Y388H     na
IVS9 c.997+2T>A   Taillandier et al. 2000 perinatal c.997+2T>A/p.C489S     na
IVS9 c.997+2T>G   Brun-Heath et al. 2005 perinatal c.997+2T>G/c.997+2T>G     na
IVS9 c.997+3A>C   Mornet et al. 1998 perinatal c.997+3A>C/c.997+3A>C     na
IVS9 c.997+3A>G   Wenkert et al. 2011 prenatal benign c.1181_1182delCT/c.997+3A>G     na
IVS9 c.998-1G>T   Taillandier et al. 2001 perinatal p.E191K/c.998-1G>T     na
10 c.1000G>C p.G334R Fauvert et al. 2009 odonto p.G334R/N 5.0 20 ++
10 c.1001G>A p.G334D Greenberg et al. 1993 perinatal p.G334D/p.G334D 0 10 ++
10 c.1010A>G p.D337G Whyte et al. 2015 childhood p.D337G/p.E191K     ++
10 c.1015G>A p.G339R Mumm et al. 2002 perinatal p.G339R/p.A176T 1.1 20 ++
10 c.1015G>C p.G339R Versailles lab. Jan 2010 adult p.G339R/p.E191K     ++
10 c.1016G>A p.G339E Versailles lab oct. 2004 infantile p.G339E/p.V128M     ++
10 c.1042G>A p.A348T Taillandier et al. 2000 infantile p.E191K/p.A348T 33.2 5 ++
10 c.1044_1055del12 p.L349_A352del Spentchian et al. 2006 perinatal p.L349_p.A352del/p.G491R     na
10 c.1062G>C p.E354D Souka et al. 2002 perinatal p.I212F/p.E354D     ++
10 c.1064T>C p.M355T Versailles lab oct. 2004 perinatal p.G221V/p.M355T     ++
10 c.1065G>A p.M355I Versailles lab. Jan. 2008 infantile p.M355I/p.R391C     ++
10 c.1068C>A p.D356E Versailles lab Apr 2011 perinatal p.D356E/p.R223Q     ++
10 c.1070G>T p.R357L Nielson et al. 2012 asymptomatic, low BMD p.R357L/N     +
10 c.1077C>G p.I359M Whyte et al. 2012 infantile p.D359M/p.D378V     ++
10 c.1101_1103delCTC p.S368del Versailles lab oct. 2004 perinatal c.1101_1103delCTC/p.T389I     na
10 c.1112C>T p.T371I Baumgartner-Sigl et al. 2007 infantile p.M226T/p.T371I     ++
10 c.1120G>A p.V374M Versailles lab oct. 2004 adult p.V374M/p.E298K 57.6 25 +
10 c.1130C>T p.A377V Mornet et al. 2001 perinatal p.A377V/p.A377V     ++
10 c.1132G>T p.D378Y Versailles lab. Apr. 2010 odonto. p.D378Y/N     ++
10 c.1132G>C p.D378H Whyte et al. 2015 childhood p.D378H/p.E191K     ++
10 c.1133A>T p.D378V Henthorn et al. 1992 infantile p.E191K/p.D378V 1.2 3 ++
10 c.1142A>G p.H381R Taillandier et al. 2000 infantile p.A40V/p.H381R     ++
10 c.1144G>A p.V382I Goseki-Sone et al. 1998 childhood p.F327L/p.V382I 0 11 ++
10 c.1162T>C p.Y388H Liu et al. 2010 odonto p.Y388H/c.997+1G>T 39.7 25 ++
10 c.1166C>T p.T389I Versailles lab oct. 2004 perinatal p.T389I/p.S368del     ++
10 c.1166C>A p.T389N Yang et al. 2013 childhood p.T389N/p.R136L 0 26 ++
10 c.1171C>T p.R391C Zurutuza et al. 1999 childhood p.E191K/p.R391C 10.3 1 ++
10 c.1172G>A p.R391H Orimo et al. 2002 childhood p.R391H/? 3.7 4 ++
10 c.1171delC p.R391VfsX12 Taillandier et al. 1999 infantile p.M62L/c.1171delC     na
10 c.1175G>C p.G392A Versailles lab. Jan. 2008 perinatal p.G392A/p.R136C     ++
10 c.1178A>T p.N393I Versailles lab March 2013 infantile moderate p.N393I/p.E191K     +
10 c.1181_1182delCT frameshift Wenkert et al. 2011 prenatal benign c.1181_1182delCT/c.997+3A>G     na
10 c.1183A>G p.I395V Wenkert et al. 2011 prenatal benign p.I395V/p.W153R     ++
10 c.1184T>C p.I395T Versailles lab Jul. 2006 perinatal p.I395T/p.E191K     ++
IVS10 c.1189+5delG   Whyte et al. 2015 childhood c.1189+5delG/p.A443V     na
11 c.1190G>A p.G397D Whyte et al. 2015 odonto. p.G397D/N     ++
11 c.1195G>T p.A399S Taillandier et al. 2001 adult p.E235G/p.A399S     ++
11 c.1196C>T p.A399V Spentchian et al. 2006 adult p.A399V/p.A33V     ++
11 c.1199C>T p.P400L Spentchian et al. 2006 infantile p.P400L/p.P400L     ++
11 c.1214_1215delCA p.T405RfsX22 Versailles lab Jul. 2006 adult c.1214_1215delCA/p.E191K     na
11 c.1216_1219delGACA p.D406RfsX77 Brun-Heath et al. 2005 perinatal c.1216_1219delGACA/?     na
11 c.1216G>A p.D406N Versailles lab Dec 2011 perinatal p.Q318X/p.D406N     -
11 c.1217A>G p.D406G Taillandier et al. 2000 odonto. p.D406G/p.R450H 14.9 5 -
11 c.1228T>C p.F410L Versailles lab oct. 2004 infantile p.F410L/p.E191K     +
11 c.1231A>G p.T411A Brun-Heath et al. 2005 perinatal p.T411A/c.926_927delTC 0.3 16 ++
11 c.1240C>A p.L414M Mumm et al. 2002 perinatal p.L414M/p.D294A 0.4 20 ++
11 c.1250A>G p.N417S Sergi et al. 2001 perinatal p.N417S/c.648+1G>A 3 20 ++
11 c.1256delC p.P419LfsX65 Taillandier et al. 2000 perinatal c.1256delC/?     na
11 c.1258G>A p.G420S Glaser et al. 2004 perinatal p.G420S/p.G420S 0.4 unp. ++
11 c.1259G>C p.G420A Fauvert et al. 2009 childhood p.G420A/p.E191K 4.2 20 ++
11 c.1268T>C p.V423A Taillandier et al. 2001 perinatal p.A116T/p.V423A 15.7 2 +
11 c.1270G>A p.V424M Versailles lab jan. 2007 adult p.V424M/p.V424M     +
11 c.1271T>C p.V424A Zhang et al. 2012 adult p.V424A/p.V424A     +
11 c.1276G>T p.G426C Mochizuki et al. 2000 infantile p.K224A/p.G426C 18.5 15 ++
11 c.1276G>A p.G426S Versailles lab Apr 2011 infantile p.G426S/p.G426S     ++
11 c.1277G>A p.G426D Mumm et al. 2002 childhood p.G426D/p.E191K     ++
11 c.1282C>T p.R428X Taillandier et al. 1999 perinatal p.R428X/p.R428X     na
11 c.1283G>C p.R428P Spentchian et al. 2006 perinatal p.R428P/c.997+2T>A     ++
11 c.1283G>A p.R428Q Versailles lab Jul. 2010 prenatal benign p.R428Q/N     ++
11 c.1283G>T p.R428L Plendl et al. 2011 adult p.R428L/?     ++
11 c.1285G>A p.E429K Versailles lab Jul. 2006 odonto. p.E429K/? 1.3 20 ++
11 c.1289A>G p.N430S Whyte et al. 2015 infantile p.N430S/p.E191K     ++
11 c.1292T>C p.V431A Versailles lab Apr 2015 odonto. p.V431A/N     +
11 c.1306T>C p.Y436H Henthorn et al. 1992 childhood p.A33V/p.Y436H     ++
11 c.1307A>G p.Y436C Taketani et al. 2013 Infantile p.Y436C/c.1559delT     ++
11 c.1307A>C p.Y436S Nielson et al. 2012 asymptomatic, low BMD p.Y436S/N     ++
12 c.1313A>T p.H438L Versailles lab oct. 2009 infantile p.H438L/p.H438L     ++
12 c.1318_1320 delAAC p.N440del Martins et al. 2013 odonto. p.R152C/p.N440del     na
12 c.1323C>A p.Y441X Hofmann et al. 2013 perinatal p.Y441X/p.R223W 1.0 24 na
12 c.1328C>T p.A443V Fauvert et al. 2009 adult p.A443V/N 1.4 20 ++
12 c.1333T>C p.S445P Mornet et al. 1998 infantile p.S445P/? 2.1 1 +
12 c.1336G>A p.A446T Versailles lab Jan 2013 perinatal p.A446T/p.A446T     ++
12 c.1349G>A p.R450H Taillandier et al. 2000 odonto. p.D406G/p.R450H     +
12 c.1348C>T p.R450C Mornet et al. 1998 infantile p.R450C/p.R450C 4.0 1 +
12 c.1354G>A p.E452K Spentchian et al. 2003 perinatal p.A111T/p.E452K 1.4 20 ++
12 c.1361A>G p.H454R Versailles lab oct. 2003 childhood p.E191K/p.H454R     ++
12 c.1363G>A p.G455S Draguet et al. 2004 adult p.G455S/p.G491R 71.0 21 ++
12 c.1364G>A p.G455D Versailles lab jan. 2007 perinatal pG455D/pG455D     ++
12 c.1366G>T p.G456W Versailles lab oct. 2003 childhood pG456W/? 0.8 20 ++
12 c.1366G>A p.G456R Ozono et al. 1996 infantile pG456R/? 1.5 unp. ++
12 c.1372G>A p.D458N Versailles lab Dec 2011 adult pD458N/pE191K     ++
12 c.1373A>G p.D458G Plendl et al. 2011 infantile pD458G/pE191K     ++
12 c.1375G>A p.V459M Taillandier et al. 2000 infantile pA51V/p.V459M     ++
12 c.1375G>T p.V459L Versailles lab oct. 2004 perinatal p.V459L/p.E452K 0 20 ++
12 c.1381G>A p.V461I Nielson et al. 2012 asymptomatic, low BMD p.V461I/N     +
12 c.1397C>T p.P466L Versailles lab oct. 2003 perinatal p.P466L/?     +
12 c.1400T>C p.M467T Versailles lab oct. 2004 infantile p.M467T/p.P307S     +
12 c.1402G>A p.A468T Spentchian et al. 2003 perinatal p.A468T/p.A468T     ++
12 c.1412_1429del18 p.L471_E476del Plendl et al. 2011 adult p.L471_p.E476del/?     na
12 c.1414C>T p.H472Y V. Buzzi, P. La Verde, Milan, Italy perinatal p.H472Y/p.T100M     ++
12 c.1417G>A p.G473S Mornet et al. 1998 perinatal p.A40V/p.G473S     ++
12 c.1426G>A p.E476K Taillandier et al. 1999 perinatal p.A111T/p.E476K     ++
12 c.1427A>G p.E476G Mornet et al. 2001 perinatal p.E476G/p.E476G     ++
12 c.1427A>C p.E476A Versailles lab March 2009 adult p.E476A/? 0.4 20 ++
12 c.1433A>T p.N478I Taillandier et al. 2000 childhood p.N478I/N 1.1 3 ++
12 c.1444C>A p.H482N Nielson et al. 2012 asymptomatic, low BMD p.H482N/N     ++
12 c.1444_1445insC p.H482Pfs Brun-Heath et al. 2005 perinatal c.1444_1445insC/p.G334D     na
12 c.1460C>T p.A487V Versailles lab July 2014 perinatal p.A487V/p.F327del     ++
12 c.1466G>C p.C489S Taillandier et al. 2000 perinatal p.C489S/c.997+2T>A 9.4 5 ++
12 c.1468A>T p.I490F Lia-Baldini et al. 2001 adult p.I490F/? 37.1 3 +
12 c.1471G>A p.G491R Mornet et al. 1998 perinatal p.G129R/p.G491R     ++
12 c.1474delG p.A492PfsX29 Brun-Heath et al. 2005 odonto c.1474delG/p.R136H     na
12 c.1553_1569del17 p.Y518Ffs Versailles lab nov. 2009 perinatal c.1553_1569del/p.D294A     na
12 c.1559delT p.L520RfsX86 Orimo et al. 1994 infantile p.E298K/c.1559delT 28 18 na


Large deletions

deletion of exon 1   Versailles lab july 2012 perinatal homozygote     na
deletion of exon 2   Versailles lab july 2013 perinatal homozygote     na
deletion of exons 3-5   Spentchian et al. 2006 perinatal homozygote     na
deletion of exon 12 (3' part)   Spentchian et al. 2006 infantile compound heterozygote
with S164L
    na

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

 

Statistics

Type of mutation Number of mutations %
Missense 224 74,6
Small deletions 33 11.0
Splicing 18 9.0
Nonsense 11 3.7
Small insertions 7 2.3
Large deletions 4 1.3
Ins/Del 2 0.7
Regulatory 1 0.4
Total 300 100

Legend to database items

Nomenclature : see the nomenclature section below.
Reference : reference of the publication reporting the mutation.
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 or pedigree evidence of dominant transmission).
N : normal allele (dominant mutation on the other chromosome, evidenced by molecular or pedigree data.
%WT : alkaline phosphatase activity of cells transfected with mutated cDNAs, expressed in percentage of the activity found in cells transfected with wild type (WT) cDNA.
ref : reference reporting transfections experiments.
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 and the Nomenclature Working Group (S.E. Antonarakis and the Nomenclature Working Group, Hum. Mut. 11:1-3, 1998): the first nucleotide (+1) corresponds to the A of the ATG initiation codon. The reference cDNA sequence is NM_000478.4

Amino acids numbering is given according to the standardized nomenclature : the first codon is the ATG initiation codon. In publications before 2008 a non-standardized nomenclature was used: 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_000478.4

p: protein numbering; c: nucleotide numbering of the coding sequence.

References: