Mutagenetix > Incidental Mutation

Incidental Mutation 'R8686:Alpl'

662029

Institutional Source

Beutler Lab

Gene Symbol

Alpl

Ensembl Gene

ENSMUSG00000028766

Gene Name

alkaline phosphatase, liver/bone/kidney

Synonyms

TNSALP, TNAP, Akp-2, Akp2

MMRRC Submission

068541-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R8686 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

137741733-137796384 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 137743801 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 341 (H341Q)

Ref Sequence

ENSEMBL: ENSMUSP00000030551 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030551]

AlphaFold

P09242

Predicted Effect

probably damaging
Transcript: ENSMUST00000030551
AA Change: H341Q

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000030551
Gene: ENSMUSG00000028766
AA Change: H341Q

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
alkPPc	52	491	4.69e-285	SMART
low complexity region	500	520	N/A	INTRINSIC

Meta Mutation Damage Score

0.9632

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

100% (58/58)

MGI Phenotype

FUNCTION: This gene encodes a preproprotein that is proteolytically cleaved to yield a signal peptide and a proproptein that is subsequently processed to generate the active mature peptide. The encoded protein is a membrane-bound glycosylated enzyme that catalyzes the hydrolysis of phosphate esters at alkaline pH. The mature peptide maintains the ratio of inorganic phosphate to inorganic pyrophosphate required for bone mineralization. Mice that lack this enzyme show symptoms of osteomalacia, softening of the bones. In humans, mutations in this gene are associated with hypophosphatasia, an inherited metabolic bone disease in which deficiency of this enzyme inhibits bone mineralization leading to skeletal defects. Mutations in the mouse gene mirror the symptoms of human hypophosphatasia. A pseudogene of this gene is present on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
PHENOTYPE: Males hemizygous for a null mutation exhibit reduced body size, shortened hindlimbs and tail, osteomalacia, and markedly reduced plasma phosphate levels due to impaired kidney reabsorption. Female heterozygotes exhibit milder symptoms. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 62 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1300017J02Rik	C	T	9: 103,259,428	A525T	probably benign	Het
Adam25	A	G	8: 40,755,484	T596A	probably benign	Het
Adamts6	A	G	13: 104,313,699	I303V	probably damaging	Het
Cachd1	G	A	4: 100,988,128	R939H	probably damaging	Het
Ccdc114	A	G	7: 45,947,692	T456A	probably benign	Het
Cd22	G	A	7: 30,870,069	R541C	probably benign	Het
Cenpf	A	T	1: 189,659,604	M660K	probably benign	Het
Cmya5	A	T	13: 93,095,380	S1067T	possibly damaging	Het
Col5a2	C	T	1: 45,421,987	G250D	probably damaging	Het
Cylc2	C	T	4: 51,229,651	T331M	unknown	Het
Dgka	A	G	10: 128,733,093	M201T	probably benign	Het
Dnajc13	T	C	9: 104,170,805	I1804V	probably benign	Het
Dym	T	A	18: 75,286,683	Y642N	probably damaging	Het
Efr3b	A	T	12: 4,000,886	D26E	probably damaging	Het
Emilin1	A	T	5: 30,917,696	K427M	possibly damaging	Het
Fam187b	T	C	7: 30,977,234	L56S	probably benign	Het
Fbxo18	C	T	2: 11,755,658	V694I	probably benign	Het
Fgd2	C	T	17: 29,379,023	T644I	probably benign	Het
G6pc	T	G	11: 101,374,707		probably null	Het
Gli2	A	G	1: 118,836,687	S1245P	probably benign	Het
Gm10696	T	C	3: 94,176,120	D128G	probably benign	Het
Gpr137b	T	C	13: 13,359,406	Y355C		Het
Ighv1-84	T	C	12: 115,980,904	D50G	probably benign	Het
Impdh1	C	A	6: 29,216,215		probably benign	Het
Irf4	A	T	13: 30,761,450	D393V	possibly damaging	Het
Kalrn	A	G	16: 34,360,935	L111P	probably damaging	Het
Lrch3	T	C	16: 32,981,853	V58A	possibly damaging	Het
Lrif1	C	T	3: 106,732,781	T394I	probably damaging	Het
Map4k1	A	G	7: 28,994,073	T434A	probably benign	Het
Mcur1	G	A	13: 43,541,717	T327M	probably damaging	Het
Mettl7b	A	T	10: 128,960,607	M111K	possibly damaging	Het
Myo9b	G	T	8: 71,334,322	S716I	probably benign	Het
Nol10	T	A	12: 17,369,771		probably benign	Het
Nos3	A	G	5: 24,368,843	T202A	possibly damaging	Het
Olfr128	T	C	17: 37,924,277	V237A	probably benign	Het
Olfr710	A	C	7: 106,944,698	M101R	probably benign	Het
Parp12	A	T	6: 39,117,922	S80T	probably benign	Het
Pde1a	C	T	2: 79,927,742	V50I	probably benign	Het
Pfkl	A	T	10: 77,997,522		probably null	Het
Phkg1	A	T	5: 129,866,215	Y207N	probably damaging	Het
Pik3r4	A	G	9: 105,658,529	T640A	possibly damaging	Het
Pip5k1c	C	A	10: 81,311,993	H411N	probably damaging	Het
Pla2g4e	A	G	2: 120,244,691	S73P	probably damaging	Het
Polr2b	T	C	5: 77,335,663	V662A	probably damaging	Het
Prss43	C	T	9: 110,829,426	R265C	possibly damaging	Het
Rap1b	A	T	10: 117,822,841	V29D	probably damaging	Het
Rraga	A	G	4: 86,576,811	E298G	probably damaging	Het
Rrp8	A	T	7: 105,733,574	I418N	probably damaging	Het
Siglecf	T	C	7: 43,355,606	V420A	probably benign	Het
Snx14	T	A	9: 88,415,693	N174I	probably damaging	Het
Speer4e	T	C	5: 14,934,115	N229S	probably benign	Het
Teddm3	A	G	16: 21,152,935	*295Q	probably null	Het
Tfap2c	A	G	2: 172,552,006	D245G	possibly damaging	Het
Tfap2d	A	G	1: 19,108,284	N191S	probably benign	Het
Unc80	A	G	1: 66,612,268	R1591G	possibly damaging	Het
Vmn1r116	T	C	7: 20,872,691	W146R	probably damaging	Het
Vps13b	C	G	15: 35,925,389	S3823R	probably damaging	Het
Wiz	T	A	17: 32,367,847	D163V	probably damaging	Het
Xylt1	G	C	7: 117,381,359	A61P	unknown	Het
Zfp521	A	C	18: 13,845,644	F571V	probably damaging	Het
Zfp664	T	A	5: 124,886,069	C176S	possibly damaging	Het
Zfyve26	T	C	12: 79,287,453	N264D	probably benign	Het

Other mutations in Alpl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01099:Alpl	APN	4	137743313	splice site	probably benign
IGL02164:Alpl	APN	4	137753979	missense	probably damaging	1.00
IGL02379:Alpl	APN	4	137742558	missense	probably damaging	1.00
IGL02632:Alpl	APN	4	137753906	missense	probably damaging	0.98
IGL02926:Alpl	APN	4	137742634	missense	probably damaging	1.00
R0492:Alpl	UTSW	4	137749576	splice site	probably null
R1157:Alpl	UTSW	4	137754020	missense	probably damaging	1.00
R2013:Alpl	UTSW	4	137755147	missense	probably benign	0.00
R2067:Alpl	UTSW	4	137749545	unclassified	probably benign
R4412:Alpl	UTSW	4	137758628	missense	possibly damaging	0.84
R4440:Alpl	UTSW	4	137747813	missense	probably damaging	1.00
R5275:Alpl	UTSW	4	137749608	missense	probably benign	0.00
R5295:Alpl	UTSW	4	137749608	missense	probably benign	0.00
R5529:Alpl	UTSW	4	137746422	missense	probably damaging	0.99
R6706:Alpl	UTSW	4	137746429	missense	probably benign	0.00
R7291:Alpl	UTSW	4	137752698	missense	probably damaging	1.00
R7693:Alpl	UTSW	4	137743809	missense	probably damaging	1.00
R7694:Alpl	UTSW	4	137743809	missense	probably damaging	1.00
R8247:Alpl	UTSW	4	137746453	missense	probably damaging	1.00
R8725:Alpl	UTSW	4	137747816	missense	probably benign
R8727:Alpl	UTSW	4	137747816	missense	probably benign
X0017:Alpl	UTSW	4	137746467	missense	probably damaging	1.00
Z1176:Alpl	UTSW	4	137754010	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACAGGCTGCTTCGCTGTATC -3'
(R):5'- ACTTGGCCATGAGATGCCTG -3'

Sequencing Primer
(F):5'- TGTATCCCAGGGACAGGCTACTC -3'
(R):5'- CCATGAGATGCCTGAGGTAGACC -3'

Posted On

2021-03-08