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 : July 24, 2014
Total number of mutations described : 280



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 280 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 Reference Clinical form in patient Genotype of patient % WT ref. E.coli
Non-standardized nomenclature Standardized nomenclature
1 c.-195C>T     Taillandier et al. 2000 perinatal c.-195C>T/C184Y     na
2 c.3G>A M-17I p.M1I Mentrup et al. 2011 adult M-17I/? 1.0 22 +
2 c.17T>A L-12X p.L6X Taillandier et al. 2000 childhood L-12X/?     na
2 c.41T>C L-4P p.L14P Versailles lab Jul 2010 adult L-4P/E174K     na
2 c.43_46delACTA   p.N16PfsX2 Versailles lab March 2011 infantile c.43_46delACTA/R206Q     na
2 c.50C> T S-1F p.S17F Mornet et al. 1998 infantile S-1F/G58S 19.0 1 na
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/N32I     na
3 c.82T>G Y11D p.Y28D Yang et al. 2013 odonto Y11D/Y371H 0 26 -
3 c.83A>G Y11C p.Y28C Taillandier et al. 2001 infantile Y11C/R119H 7.2 2 -
3 c.88C>T R13X p.R30X Versailles lab Dec 2010 perinatal R13X/G112R     na
3 c.94C>T Q15X p.Q32X Versailles lab. Apr 2011 perinatal Q15X/c.648+1G>A     na
3 c.98C>T A16V p.A33V Henthorn et al. 1992 childhood A16V/Y419H     -
3 c.106A>C T19P p.T36P Versailles lab Nov 2008 perinatal T19P/T19P     +
3 c.110T>C L20P p.L37P Versailles lab oct. 2003 perinatal L20P/L20P     +
3 c.119C>T A23V p.A40V Mornet et al. 1998 perinatal A23V/G456S 2.3 1 +
3 c.130C>T Q27X p.Q44X Mornet E, unpublished perinatal Q27X/c.662insG     na
3 c.146A>T N32I p.N49I Versailles lab May 2012 perinatal N32I/c.69_74delGAAAGA     -
3 c.151G>T A34S p.A51S Mumm et al. 2002 infantile A34S/T117H     +
3 c.152C>T A34V p.A51V Taillandier et al. 2001 infantile A34V/V442M     +
4 c.184A>T M45L p.M62L Taillandier et al. 1999 infantile M45L/c.1172delC 27.4 1 +
4 c.184A>G M45V p.M62V Spentchian et al. 2003 infantile M45V/M45V     +
4 c.186G>C M45I p.M62I Taillandier et al.2005 childhood M45I/E174K 0 16 +
4 c.187G>C G46R p.G63R Spentchian et al. 2003 infantile G46R/G46R     +
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 G46V p.G63V Lia-Baldini et al. 2001 infantile G46V/N 0.8 3 +
4 c.203C>T T51M p.T68M Orimo et al. 2002 childhood T51M/A160T 5.2 4 +
4 c.211C>T R54C p.R71C Henthorn et al. 1992 infantile R54C/D277A 0 17 +
4 c.211C>A R54S p.R71S Orimo et al. 2002 childhood R54S/? 2.9 4 +
4 c.212G>C R54P p.R71P Henthorn et al. 1992 perinatal R54P/Q190P     +
4 c.212G>A R54H p.R71H Taillandier et al. 2001 perinatal A23V/R54H 1.0 20 +
4 c.215T>C I55T p.I72T Versailles lab oct. 2004 odonto I55T/N 5.1 20 -
4 c.217_219delCTC L56del p.L73del Versailles lab aug. 2013 asymptomatic* F56del/N     na
4 c.223G>A G58S p.G75S Mornet et al. 1998 infantile S-1F/G58S 3.5 1 +
4 c.227A>G Q59R p.Q76R Mornet et al. 2001 infantile Q59R/T117N     -
4 c.242delC   p.P81LfsX41 Versailles lab Jul 2009 perinatal c.240delC/c.240delC     na
4 c.247G>T E66X p.E83X Versailles lab Apr 2011 infantile E66X/E66X     na
4 c.251A>T E67V p.E84V Wei et al. 2010 odonto E67V/N     -
4 c.262G>A E71K p.E88K Mohn et al. 2011 infantile E71K/P290L     -
4 c.277C>T P76S p.P93S Peach et al. 2007 prenat. benign P76S/T117H     -
IVS4 c.297+3G>T     Versailles lab. Jan 2011 infantile c.297+3G>T/T83M     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      
5 c.299C>T T83M p.T100M Mornet et al. 2001 infantile T83M/E174K 1.3 20 +
5 c.301T>G Y84D p.Y101D Versailles lab. Feb 2012 Odonto Y84D/N     -
5 c.303_311del N85_N87del p.N102_N104del Versailles lab Jul 2007 perinatal c.303_311del/G474R     na
5 c.318G>C Q89H p.Q106H Balasubramaniam et al. 2010 infantile Q89H/Q89H     -
5 c.323C>T P91L p.P108L Herasse et al. 2003 odonto P91L/N 0.4 unp. -
5 c.331G>A A94T p.A111T Goseki-Sone et al. 1998 odonto A94T/? 2.0 20 +
5 c.334G>A G95S p.G112S Witters et al. 2004 infantile G95S/R374C     -
5 c.335_340dupGCACCG G95_96dup p.G112_113dup Wenkert et al. 2011 prenatal benign G95_96dup/E174K     na
5 c.340G>A A97T p.A114T Mumm et al. 2001 infantile A97T/D277A     +
5 c.341C>G A97G p.A114G Draguet et al. 2004 perinatal

A97G+c.348_349insACCGTC
/G309R

    +
5 c.346G>T A99S p.A116S Versailles lab Jul 2007 adult A99S/N400S     +
5 c.346G>A A99T p.A116T Hu et al. 2000 adult A99T/N 0.8 3 +
5 c.348_349insACCGTC   p.A116_Y117insTV Draguet et al. 2004 perinatal A97G+c.348_349insACCGTC
/G309R
    na
5 c.343_348dupACCGCC   p.T115_A116dup Versailles lab March 2009 odonto c.348_349insACCGCC      
5 c.350A>G Y100C p.Y117C Whyte et al. 2009 childhood Y100C/T117H     -
5 c.358G>A G103R p.G120R Mornet et al. 1998 perinatal G103R/648+1G>A     +
5 c.368C>A A106D p.A123D Spentchian et al. 2006 perinatal A106D/S249_H250del     -
5 c.382G>A V111M p.V128M Mumm et al. 2002 perinatal V111M/R206W     -
5 c.385G>A G112R p.G129R Mornet et al. 1998 perinatal G112R/G474R     +
5 c.388_391delGTAA   p.V130AfsX34 Spentchian et al. 2003 perinatal E294K/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/A331T     na
5 c.394G>A A115T p.A132T Versailles lab Jul 2006 adult A115T/E174K      
5 c.395C>T A115V p.A132V Watanabe et al. 2001 adult A115V/? 16.9 14 -
5 c.400_401AC>CA T117H p.T134H Mumm et al. 2002 perinatal T117H/F310del     -
5 c.401C>A T117N p.T134N Taillandier et al. 2000 perinatal T117N/T117N 20.5 5 -
5 c.406C>T R119C p.R136C Versailles lab oct. 2003 odonto R119C/R119H     -
5 c.407G>A R119H p.R136H Taillandier et al. 1999 infantile R119H/G145V 33.4 1 -
5 c.407G>T R119L p.R136L Yang et al. 2013 childhood R119L/T372N 35 26 -
5 c.422C>T T124I p.T141I Versailles lab Jul 2008 infantile T124I/P290L     +
5 c.442A>G T131A p.T148A Michigami et al. 2005 perinatal T131A/?     -
5 c.443C>T T131I p.T148I Spentchian et al. 2003 infantile T131I/G145S     -
5 c.454C>T R135C p.R152C Versailles lab Nov. 2009 adult R135C/R167W     -
5 c.457T>C W136R p.W153R Wenkert et al. 2011 prenatal benign I395V/W136R     -
5 c.472+1G>A     Liu et al. 2010 odonto c.472+1G>A/V357M     na
6 c.480delT     Versailles lab. Jan. 2008 perinatal c.480delT/R206W     na
6 c.484G>A G145S p.G162S Spentchian et al. 2003 infantile T131I/G145S     +
6 c.485G>T G145V p.G162V Taillandier et al. 1999 infantile R119H/G145V 1.3 1 +
6 c.491T>G V147G p.V164G Versailles lab March 2009 infantile V147G/D277A     +
6 c.500C>T T150M p.T167M Versailles lab Oct. 2003 infantile T150M/E174K 0   +
6 c.508A>G N153D p.N170D Mornet et al. 1998 perinatal N153D/N153D 0 13 -
6 c.511C>T H154Y p.H171Y Taillandier et al. 1999 infantile H154Y/E174K 2.1 1 -
6 c.512A>G H154R p.H171R Mornet E, unpublished adult H154R/E174K     -
6 c.526G>A A159T p.A176T Taillandier et al. 2000 childhood A159T/R229S 45.4 5 +
6 c.529G>A A160T p.A177T Goseki-Sone et al. 1998 adult A160T/F310L 83.8 4 -
6 c.535G>A A162T p.A179T Weiss et al. 1988 perinatal A162T/A162T 18 6 +
6 c.542C>T S164L p.S181L Lia-Baldini et al. 2001 infantile S164L/del(ex12) 1.3 3 -
6 c.544delG   p.A182LfsX16 Taillandier et al. 1999 perinatal G232V/544delG     na
6 c.547G>C D166H p.D183H Versailles lab Nov 2008 infantile D166H/D277A     -
6 c.550C>T R167W p.R184W Mornet et al. 1998 perinatal R167W/W253X 0.6 3 +
6 c.551G>A R167Q p.R184Q Versailles lab. Nov. 2013 Infantile R167Q/T51M     +
6 c.567C>A D172E p.D189E Spentchian et al. 2003 perinatal D172E/D172E     -
6 c.568_570delAAC N173del p.N190del Michigami et al. 2005 perinatal c.1559delT/N173del     -
6 c.571G>A E174K p.E191K Henthorn et al. 1992 infantile E174K/D361V 88.0 1 -
6 c.572A>G E174G p.E191G Goseki-Sone et al. 1998 odonto E174G/c.1559delT     -
6 c.575T>C M175T p.M192T Versailles lab Jul 2007 infantile M175T/E294K     -
6 c.577C>G P176A p.P193A Mumm et al. 2002 adult A97T/P176A     +
6 c.599G>A G183D p.G200D Versailles lab April 2014 adult G183D/N     +
6 c.602G>A C184Y p.C201Y Taillandier et al. 1999 perinatal c.-195C>T/C184Y 0 23 -
6 c.609C>G D186E p.D203E Versailles lab oct. 2004 perinatal D186E/D186E     -
6 c.614C>T A188V p.A205V Versailles lab aug. 2013 asymptomatic* A188V/N     -
6 c.620A>C Q190P p.Q207P Henthorn et al. 1992 perinatal R54P/Q190P     +
6 c.622C>T L191F p.L208F Versailles lab april 2009 perinatal L191F/L191F     +
6 c.630_637dupTAACATCA   p.R213IfsX8 Versailles lab June 2011 perinatal c.630_637dupTAACATCA/c.792G>A     na
6 c.631A>G N194D p.N211D Taillandier et al. 2001 infantile A99T/N194D     +
6 c.634A>T I195F p.I212F Souka et al. 2002 perinatal I195F/E337D     -
6 c.644T>C I198T p.I215T Versailles lab. march 2011 infantile I198T/S164L     -
IVS6 c.648+1G>T     Brun-Heath et al. 2005 perinatal c.648+1G>T/D277A      
IVS6 c.648+1G>A     Mornet et al. 1998 perinatal G103R/c.648+1G>A     na
IVS6 c.648+2_3insT     Versailles lab jan 2013 perinatal c.648+2_3insT/A382V     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/F310del     na
7 c.653T>C I201T p.I218T

Utsch et al., 2009

perinatal I201T/R374C 3.7 19 -
7 c.655A>G M202V p.M219V Yang et al. 2013 odonto M202V/A94T 75 26 -
7 c.658G>A G203R p.G220R Versailles lab Dec 2011 perinatal G203R/G203R     +
7 c.659G>T G203V p.G220V Taillandier et al. 2001 odonto E174K/G203V     +
7 c.659G>C G203A p.G220A Spentchian et al. 2003 perinatal G203A/G203A     +
7 c.661G>C G204R p.G221R Versailles lab March 2009 perinatal G204R/?     +
7 c.662_663insG   p.G222WfsX10 Mornet E, unpublished perinatal Q27X/662_663insG     na
7 c.662delG   p.G221VfsX56 Spentchian et al. 2003 perinatal R255L/c.662delG     na
7 c.662G>T G204V p.G221V Versailles lab oct. 2004 perinatal G204V/M338T     +
7 c.667C>T R206W p.R223W Mornet et al. 1998 perinatal R206W/? 2.8 3 -
7 c.668G>A R206Q p.R223Q Mumm et al. 2002 perinatal R206Q/deletion 2.9 25 -
7 c.670A>G K207E p.K224E Mochizuki et al. 2000 infantile K207E/G409C 43 15 +
7 c.677T>C M209T p.M226T Baumgartner-Sigl et al. 2007 infantile M209T/T354I     -
7 c.704A>G E218G p.E235G Taillandier et al. 2001 adult E218G/A382S 3.6 7 +
7 c.738G>T R229S p.R246S Taillandier et al. 2000 childhood A159T/R229S 4.4 5 -
7 c.746G>T G232V p.G249V Fedde et al. 1996 perinatal G232V/N 34.5 3 +
7 c.791A>G K247R p.K264R Brun-Heath et al. 2007 perinatal K247R/D361V     -
7 c.792G>A K247K p.K264K Versailles lab june 2011 perinatal K247K/c.630_637dupTAACATCA     na
8 c.797_802del S249_H250del p.S266_H267del Spentchian et al. 2006 perinatal A106D/S249_H250del      
8 c.809G>A W253X p.W270X Mornet et al. 1998 perinatal R167W/W253X 1.2 1 na
8 c.814C>T R255C p.R272C Spentchian et al. 2006 perinatal R255C/T117H     -
8 c.814delC   p.R272AfsX5 Versailles lab June 2011 perinatal c.814delT/H364R     na
8 c.815G>T R255L p.R272L Spentchian et al. 2003 perinatal R255L/c.662delG     -
8 c.815G>A R255H p.R272H Brun-Heath et al. 2005 infantile R255H/R255H 6.8 16 -
8 c.824T>C L258P p.L275P Orimo et al. 2002 childhood L258P/A160T 3.3 4 -
8 c.853_854insGATC Y268X p.Y285X Michigami et al. 2005 perinatal c1559delT/Y268X     na
IVS8 c.862+5G>A     Taillandier et al. 1999 infantile c.862+5G>A/c.862+5G>A     na
9 c.865C>T L272F p.L289F Sugimoto et al. 1998 infantile L272F/? 50 8 -
9 c.871G>A E274K p.E291K Mornet et al. 1998 infantile E174K/E274K 8.3 1 -
9 c.871G>T E274X p.E291X Taillandier et al. 2000 perinatal A94T/E274X     -
9 c.871G>C E274Q p.E291Q Versailles lab Jun 2010 perinatal E274Q/E274Q     -
9 c.874C>A P275T p.P292T Brun-Heath et al. 2005 infantile P275T/A16V 4.0 16 +
9 c.875_881delCAGGGGAinsT     Belachew et al. 2013 perinatal c.875_881delCAGGGGAinsT/c.1559delT     na
9 c.876_881delAGGGGA G276_D277del p.G293_D294del Spentchian et al. 2003 perinatal G276_D277del/c.962delG     na
9 c.880G>T D277Y p.D294Y Taillandier et al. 2001 infantile A159T/D277Y     -
9 c.881A>C D277A p.D294A Henthorn et al. 1992 infantile R54C/D277A 35 17 -
9 c.883A>G M278V p.M295V Mornet et al. 2001 childhood E174K/M278V     -
9 c.884T>C M278T p.M295T Brun-Heath et al. 2005 perinatal M278T/R206W 8.5 16 -
9 c.885G>A M278I p.M295I Michigami et al. 2005 perinatal M278I/c.1559delT     -
9 c.886C>T Q279X p.Q296X Plendl et al. 2011 adult p.Q296X/?     na
9 c.889T>G Y280D p.Y297D Brun-Heath et al. 2005 childhood R119H/Y280D 1.3 16 -
9 c.889T>C Y280H p.Y297H Bertola et al. 2009 perinatal Y280H/c.648+1G>A     -
9 c.891C>A Y280X p.Y297X Balasubramaniam et al. 2010 Infantile Y280X/G474R     na
9 c.892G>A E281K p.E298K Orimo et al. 1994 infantile E281K/1559delT     -
9 c.896T>C L282P p.L299P Versailles lab oct. 2003 infantile L282P/L282P 9.7 15 -
9 c.917A>T D289V p.D306V Taillandier et al. 1999 infantile D289V/D289V 0 12 -
9 c.919C>T P290S p.P307S Versailles lab oct. 2004 infantile P290S/M450T     +
9 c.920C>T P290L p.P307L Versailles lab Jul. 2006 childhood P290L/S164L      
9 c.928_929delTC   p.S310RfsX27 Brun-Heath et al. 2005 perinatal T394A/c.928_929delTC      
9 c.931G>A E294K p.E311K Spentchian et al. 2003 perinatal E294K/c.388_391delGTAA     -
9 c.952C>T Q301X p.Q318X Versailles lab Dec 2011 perinatal Q301X/D389N     na
9 c.963delG   p.K322RfsX44 Spentchian et al. 2003 perinatal G276_D277del/c.963delG     na
9 c.969C>G N306K p.N323K Versailles lab oct. 2009 childhood N306K/c.648+1G>A     +
9 c.976G>C G309R p.G326R Litmanovitz et al. 2002 perinatal G309R/E274K     +
9 c.977G>T G309V p.G326V Versailles lab Jul 2008 perinatal G309V/G309V     +
9 c.984_986delCTT F310del p.F328del Orimo et al. 1997 infantile F310del/c.1559delT ~10 15 +
9 c.979T>G F310C p.F327C Mornet et al. 2001 perinatal T117N/F310C     +
9 c.979_980TT>GG F310G p.F327G Taillandier et al. 2001 adult E174K/F310G     +
9 c.979T>C F310L p.F327L Ozono et al. 1996 infantile F310L/G439R 72 9 +
9 c.982T>C F311L p.F328L Michigami et al. 2005 perinatal non-lethal F311L/T83M ~10 15 +
9 c.997+1G>T     Liu et al. 2010 odonto c.997+1G>T/Y371H     na
IVS9 c.997+2T>A     Taillandier et al. 2000 perinatal c.997+2T>A/C472S     na
IVS9 c.997+2T>G     Brun-Heath et al. 2005 perinatal c.997+2T>G/c.997+2T>G      
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      
IVS9 c.998-1G>T     Taillandier et al. 2001 perinatal E174K/c.998-1G>T     na
10 c.1000G>C G317R p.G334R Fauvert et al. 2009 odonto G317R/N 5.0 20 -
10 c.1001G>A G317D p.G334D Greenberg et al. 1993 perinatal G317D/G317D 0 10 -
10 c.1015G>A G322R p.G339R Mumm et al. 2002 perinatal G322R/A159T 1.1 20 -
10 c.1015G>C G322R p.G339R Versailles lab. Jan 2010 adult G322R/E174K     -
10 c.1016G>A G322E p.G339E Versailles lab oct. 2004 infantile G322E/V111M     -
10 c.1042G>A A331T p.A348T Taillandier et al. 2000 infantile E174K/A331T 33.2 5 -
10 c.1044_1055del12 L332_A335del p.L349_A352del Spentchian et al. 2006 perinatal L332_A335del/G474R      
10 c.1062G>C E337D p.E354D Souka et al. 2002 perinatal I195F/E337D     +
10 c.1064T>C M338T p.M355T Versailles lab oct. 2004 perinatal G204V/M338T     -
10 c.1065G>A M338I p.M355I Versailles lab. Jan. 2008 infantile M338I/R374C     -
10 c.1068C>A D339E p.D356E Versailles lab Apr 2011 perinatal D339E/R206Q     +
10 c.1077C>G I342M p.I359M Whyte et al. 2012 infantile D342M/D361V     -
10 c.1101_1103delCTC S351del p.S368del Versailles lab oct. 2004 perinatal c.1101_1103delCTC/T372I      
10 c.1112C>T T354I p.T371I Baumgartner-Sigl et al. 2007 infantile M209T/T354I     -
10 c.1120G>A V357M p.V374M Versailles lab oct. 2004 adult V357M/E281K 57.6 25 +
10 c.1130C>T A360V p.A377V Mornet et al. 2001 perinatal A360V/A360V     +
10 c.1132G>T D361Y p.D378Y Versailles lab. Apr. 2010 odonto. D361Y/N     +
10 c.1133A>T D361V p.D378V Henthorn et al. 1992 infantile E174K/D361V 1.2 3 +
10 c.1142A>G H364R p.H381R Taillandier et al. 2000 infantile A23V/H364R     +
10 c.1144G>A V365I p.V382I Goseki-Sone et al. 1998 childhood F310L/V365I 0 11 +
10 c.1162T>C Y371H p.Y388H Liu et al. 2010 odonto Y371H/c.997+1G>T 39.7 25 -
10 c.1166C>T T372I p.T389I Versailles lab oct. 2004 perinatal T372I/S351del     -
10 c.1166C>A T372N p.T389N Yang et al. 2013 childhood T372N/R119L 0 26 -
10 c.1171C>T R374C p.R391C Zurutuza et al. 1999 childhood E174K/R374C 10.3 1 -
10 c.1172G>A R374H p.R391H Orimo et al. 2002 childhood R374H/? 3.7 4 -
10 c.1171delC   p.R391VfsX12 Taillandier et al. 1999 infantile M45L/c.1171delC     na
10 c.1175G>C G375A p.G392A Versailles lab. Jan. 2008 perinatal G375A/R119C     -
10 c.1178A>T N376I p.N393I Versailles lab March 2013 infantile moderate p.N393I/p.E191K     -
10 c.1181_1182delCT frameshift frameshift Wenkert et al. 2011 prenatal benign c.1181_1182delCT/c.997+3A>G      
10 c.1183A>G I378V p.I395V Wenkert et al. 2011 prenatal benign I395V/W136R     +
10 c.1184T>C I378T p.I395T Versailles lab Jul. 2006 perinatal I378T/E174K     +
11 c.1195G>T A382S p.A399S Taillandier et al. 2001 adult E218G/A382S     -
11 c.1196C>T A382V p.A399V Spentchian et al. 2006 adult A382V/A16V     -
11 c.1199C>T P383L p.P400L Spentchian et al. 2006 infantile P383L/P383L     +
11 c.1214_1215delCA   p.T405RfsX22 Versailles lab Jul. 2006 adult c.1214_1215delCA/E174K      
11 c.1216_1219delGACA   p.D406RfsX77 Brun-Heath et al. 2005 perinatal c.1216_1219delGACA/?      
11 c.1216G>A D389N p.D406N Versailles lab Dec 2011 perinatal Q301X/D389N     +
11 c.1217A>G D389G p.D406G Taillandier et al. 2000 odonto. D389G/R433H 14.9 5 +
11 c.1228T>C F393L p.F410L Versailles lab oct. 2004 infantile F393L/E174K     -
11 c.1231A>G T394A p.T411A Brun-Heath et al. 2005 perinatal T394A/c.926_927delTC 0.3 16 -
11 c.1240C>A L397M p.L414M Mumm et al. 2002 perinatal L397M/D277A 0.4 20 -
11 c.1250A>G N400S p.N417S Sergi et al. 2001 perinatal N400S/c.648+1G>A 3 20 +
11 c.1256delC   p.P419LfsX65 Taillandier et al. 2000 perinatal c.1256delC/?     na
11 c.1258G>A G403S p.G420S Glaser et al. 2004 perinatal G403S/G403S 0.4 unp. -
11 c.1259G>C G403A p.G420A Fauvert et al. 2009 childhood G403A/E174K 4.2 20 -
11 c.1268T>C V406A p.V423A Taillandier et al. 2001 perinatal A99T/V406A 15.7 2 -
11 c.1270G>A V407M p.V424M Versailles lab jan. 2007 adult V407M/V407M     -
11 c.1271T>C V407A p.V424A Zhang et al. 2012 adult V407A/V407A     -
11 c.1276G>T G409C p.G426C Mochizuki et al. 2000 infantile K207A/G409C 18.5 15 -
11 c.1276G>A G409S p.G426S Versailles lab Apr 2011 infantile G409S/G409S     -
11 c.1277G>A G409D p.G426D Mumm et al. 2002 childhood G409D/E174K     -
11 c.1282C>T R411X p.R428X Taillandier et al. 1999 perinatal R411X/R411X     na
11 c.1283G>C R411P p.R428P Spentchian et al. 2006 perinatal R411P/c.997+2T>A     -
11 c.1283G>A R411Q p.R428Q Versailles lab Jul. 2010 prenatal benign R411Q/N     -
11 c.1283G>T p.R411L p.R428L Plendl et al. 2011 adult R411L/?     -
11 c.1285G>A E412K p.E429K Versailles lab Jul. 2006 odonto. E412K/? 1.3 20  
11 c.1306T>C Y419H p.Y436H Henthorn et al. 1992 childhood A16V/Y419H     na
11 c.1307A>G Y419C p.Y436C Taketani et al. 2013 Infantile Y419C/c.1559delT     na
12 c.1313A>T H421L p.H438L Versailles lab oct. 2009 infantile H421L/H421L     -
12 c.1318_1320 delAAC N423del p.N440del Martins et al. 2013 odonto. R135C/N423del     na
12 c.1323C>A Y424X p.Y441X Hofmann et al. 2013 perinatal Y424X/R206W 1.0 24 na
12 c.1328C>T A426V p.A443V Fauvert et al. 2009 adult A426V/N 1.4 20 -
12 c.1333T>C S428P p.S445P Mornet et al. 1998 infantile S428P/? 2.1 1 -
12 c.1336G>A A429T p.A446T Versailles lab Jan 2013 perinatal A446T/A446T     -
12 c.1349G>A R433H p.R450H Taillandier et al. 2000 odonto. D389G/R433H     -
12 c.1348C>T R433C p.R450C Mornet et al. 1998 infantile R433C/R433C 4.0 1 -
12 c.1354G>A E435K p.E452K Spentchian et al. 2003 perinatal A94T/E435K 1.4 20 +
12 c.1361A>G H437R p.H454R Versailles lab oct. 2003 childhood E174K/H437R     +
12 c.1363G>A G438S p.G455S Draguet et al. 2004 adult G438S/G474R 71.0 21 -
12 c.1364G>A G438D p.G455D Versailles lab jan. 2007 perinatal G438D/G438D     -
12 c.1366G>T G439W p.G456W Versailles lab oct. 2003 childhood G439W/? 0.8 20 +
12 c.1366G>A G439R p.G456R Ozono et al. 1996 infantile G439R/? 1.5 unp. +
12 c.1372G>A D441N p.D458N Versailles lab Dec 2011 adult D441N/E174K     +
12 c.1373A>G D441G p.D458G Plendl et al. 2011 infantile D441G/E174K     +
12 c.1375G>A V442M p.V459M Taillandier et al. 2000 infantile A34V/V442M     +
12 c.1375G>T V442L p.V459L Versailles lab oct. 2004 perinatal V442L/E435K 0 20 -
12 c.1397C>T P449L p.P466L Versailles lab oct. 2003 perinatal P449L/?     +
12 c.1400T>C M450T p.M467T Versailles lab oct. 2004 infantile M450T/P290S     -
12 c.1402G>A A451T p.A468T Spentchian et al. 2003 perinatal A451T/A451T     +
12 c.1412_1429del18 L454_E459del p.L471_E476del Plendl et al. 2011 adult L454_E459del/?     na
12 c.1414C>T H455Y p.H472Y V. Buzzi, P. La Verde, Milan, Italy perinatal H455Y/T83M     -
12 c.1417G>A G456S p.G473S Mornet et al. 1998 perinatal A23V/G456S     +
12 c.1426G>A E459K p.E476K Taillandier et al. 1999 perinatal A94T/E459K     +
12 c.1427A>G E459G p.E476G Mornet et al. 2001 perinatal E459G/E459G     +
12 c.1427A>C E459A p.E476A Versailles lab March 2009 adult E459A/? 0.4 20 +
12 c.1433A>T N461I p.N478I Taillandier et al. 2000 childhood N461I/N 1.1 3 -
12 c.1444_1445insC   p.H482Pfs Brun-Heath et al. 2005 perinatal c.1444_1445insC/G317D      
12 c.1460C>T A470V p.A487V Versailles lab July 2014 perinatal A470V/F310del     -
12 c.1466G>C C472S p.C489S Taillandier et al. 2000 perinatal C472S/c.997+2T>A 9.4 5 -
12 c.1468A>T I473F p.I490F Lia-Baldini et al. 2001 adult I473F/? 37.1 3 -
12 c.1471G>A G474R p.G491R Mornet et al. 1998 perinatal G112R/G474R     -
12 c.1474delG   p.A492PfsX29 Brun-Heath et al. 2005 odonto c.1474delG/R119H      
12 c.1553_1569del17   p.Y518Ffs Versailles lab nov. 2009 perinatal c.1553_1569del/D277A      
12 c.1559delT   p.L520RfsX86 Orimo et al. 1994 infantile E281K/c.1559delT 28 18 na
Large deletions
deletion of exon 1     Versailles lab july 2012 perinatal homozygote      
deletion of exon 2     Versailles lab july 2013 perinatal homozygote      
deletion of exons 3-5     Spentchian et al. 2006 perinatal homozygote      
deletion of exon 12 (3' part)     Spentchian et al. 2006 infantile compound heterozygote
with S164L
     

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

 

Statistics

Type of mutation Number of mutations %
Missense 208 74.3
Small deletions 31 11.1
Splicing 16 5.7
Nonsense 11 3.9
Small insertions 7 2.5
Large deletions 4 1.4
Ins/Del 2 0.7
Regulatory 1 0.4
Total 280 100

Legend to database items

Nomenclature : see the nomenclature section below.
Reference : reference of the publication describing the mutation.
Clinical form in patient : clinical form of the patient in whom the mutation was detected for the first time.
Genotype of patient : genotype of the patient in whom the mutation was detected for the first time (non-standardized nomenclature)
? 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.
E.coli : conservation in E.coli of residues affected by mutations. na, not applicable ; +, conserved residue ; -, residue not conserved.

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 both the non-standardized and standardized nomenclatures :

Non-standardized nomenclature: according to Weiss et al. 1988; The nomenclature takes into account of a 17-residues signal peptide, i.e. the ATG initiation codon is numbered as residue minus (-)17.
Standardized nomenclature: according to the recommandations of the Human Genome Variation Society (HGVS): the first codon is the ATG initiation codon.
p: protein numbering; c: nucleotide numbering of the coding sequence.

References: