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

TNAP, Akp-2, ALP, TNSALP, 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

137469044-137523695 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 137471112 bp (GRCm39)

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
Adam25	A	G	8: 41,208,521 (GRCm39)	T596A	probably benign	Het
Adamts6	A	G	13: 104,450,207 (GRCm39)	I303V	probably damaging	Het
Cachd1	G	A	4: 100,845,325 (GRCm39)	R939H	probably damaging	Het
Cd22	G	A	7: 30,569,494 (GRCm39)	R541C	probably benign	Het
Cenpf	A	T	1: 189,391,801 (GRCm39)	M660K	probably benign	Het
Cmya5	A	T	13: 93,231,888 (GRCm39)	S1067T	possibly damaging	Het
Col5a2	C	T	1: 45,461,147 (GRCm39)	G250D	probably damaging	Het
Cylc2	C	T	4: 51,229,651 (GRCm39)	T331M	unknown	Het
Dgka	A	G	10: 128,568,962 (GRCm39)	M201T	probably benign	Het
Dnajc13	T	C	9: 104,048,004 (GRCm39)	I1804V	probably benign	Het
Dym	T	A	18: 75,419,754 (GRCm39)	Y642N	probably damaging	Het
Efr3b	A	T	12: 4,050,886 (GRCm39)	D26E	probably damaging	Het
Emilin1	A	T	5: 31,075,040 (GRCm39)	K427M	possibly damaging	Het
Fam187b	T	C	7: 30,676,659 (GRCm39)	L56S	probably benign	Het
Fbh1	C	T	2: 11,760,469 (GRCm39)	V694I	probably benign	Het
Fgd2	C	T	17: 29,597,997 (GRCm39)	T644I	probably benign	Het
G6pc1	T	G	11: 101,265,533 (GRCm39)		probably null	Het
Gli2	A	G	1: 118,764,417 (GRCm39)	S1245P	probably benign	Het
Gpr137b	T	C	13: 13,533,991 (GRCm39)	Y355C		Het
Ighv1-84	T	C	12: 115,944,524 (GRCm39)	D50G	probably benign	Het
Impdh1	C	A	6: 29,216,214 (GRCm39)		probably benign	Het
Inhca	C	T	9: 103,136,627 (GRCm39)	A525T	probably benign	Het
Irf4	A	T	13: 30,945,433 (GRCm39)	D393V	possibly damaging	Het
Kalrn	A	G	16: 34,181,305 (GRCm39)	L111P	probably damaging	Het
Lrch3	T	C	16: 32,802,223 (GRCm39)	V58A	possibly damaging	Het
Lrif1	C	T	3: 106,640,097 (GRCm39)	T394I	probably damaging	Het
Map4k1	A	G	7: 28,693,498 (GRCm39)	T434A	probably benign	Het
Mcur1	G	A	13: 43,695,193 (GRCm39)	T327M	probably damaging	Het
Myo9b	G	T	8: 71,786,966 (GRCm39)	S716I	probably benign	Het
Nol10	T	A	12: 17,419,772 (GRCm39)		probably benign	Het
Nos3	A	G	5: 24,573,841 (GRCm39)	T202A	possibly damaging	Het
Odad1	A	G	7: 45,597,116 (GRCm39)	T456A	probably benign	Het
Or14j7	T	C	17: 38,235,168 (GRCm39)	V237A	probably benign	Het
Or2d4	A	C	7: 106,543,905 (GRCm39)	M101R	probably benign	Het
Parp12	A	T	6: 39,094,856 (GRCm39)	S80T	probably benign	Het
Pde1a	C	T	2: 79,758,086 (GRCm39)	V50I	probably benign	Het
Pfkl	A	T	10: 77,833,356 (GRCm39)		probably null	Het
Phkg1	A	T	5: 129,895,056 (GRCm39)	Y207N	probably damaging	Het
Pik3r4	A	G	9: 105,535,728 (GRCm39)	T640A	possibly damaging	Het
Pip5k1c	C	A	10: 81,147,827 (GRCm39)	H411N	probably damaging	Het
Pla2g4e	A	G	2: 120,075,172 (GRCm39)	S73P	probably damaging	Het
Polr2b	T	C	5: 77,483,510 (GRCm39)	V662A	probably damaging	Het
Prss43	C	T	9: 110,658,494 (GRCm39)	R265C	possibly damaging	Het
Rap1b	A	T	10: 117,658,746 (GRCm39)	V29D	probably damaging	Het
Rraga	A	G	4: 86,495,048 (GRCm39)	E298G	probably damaging	Het
Rrp8	A	T	7: 105,382,781 (GRCm39)	I418N	probably damaging	Het
Siglecf	T	C	7: 43,005,030 (GRCm39)	V420A	probably benign	Het
Snx14	T	A	9: 88,297,746 (GRCm39)	N174I	probably damaging	Het
Speer4e1	T	C	5: 14,984,129 (GRCm39)	N229S	probably benign	Het
Spopfm2	T	C	3: 94,083,427 (GRCm39)	D128G	probably benign	Het
Teddm3	A	G	16: 20,971,685 (GRCm39)	*295Q	probably null	Het
Tfap2c	A	G	2: 172,393,926 (GRCm39)	D245G	possibly damaging	Het
Tfap2d	A	G	1: 19,178,508 (GRCm39)	N191S	probably benign	Het
Tmt1b	A	T	10: 128,796,476 (GRCm39)	M111K	possibly damaging	Het
Unc80	A	G	1: 66,651,427 (GRCm39)	R1591G	possibly damaging	Het
Vmn1r116	T	C	7: 20,606,616 (GRCm39)	W146R	probably damaging	Het
Vps13b	C	G	15: 35,925,535 (GRCm39)	S3823R	probably damaging	Het
Wiz	T	A	17: 32,586,821 (GRCm39)	D163V	probably damaging	Het
Xylt1	G	C	7: 116,980,594 (GRCm39)	A61P	unknown	Het
Zfp521	A	C	18: 13,978,701 (GRCm39)	F571V	probably damaging	Het
Zfp664	T	A	5: 124,963,133 (GRCm39)	C176S	possibly damaging	Het
Zfyve26	T	C	12: 79,334,227 (GRCm39)	N264D	probably benign	Het

Other mutations in Alpl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01099:Alpl	APN	4	137,470,624 (GRCm39)	splice site	probably benign
IGL02164:Alpl	APN	4	137,481,290 (GRCm39)	missense	probably damaging	1.00
IGL02379:Alpl	APN	4	137,469,869 (GRCm39)	missense	probably damaging	1.00
IGL02632:Alpl	APN	4	137,481,217 (GRCm39)	missense	probably damaging	0.98
IGL02926:Alpl	APN	4	137,469,945 (GRCm39)	missense	probably damaging	1.00
R0492:Alpl	UTSW	4	137,476,887 (GRCm39)	splice site	probably null
R1157:Alpl	UTSW	4	137,481,331 (GRCm39)	missense	probably damaging	1.00
R2013:Alpl	UTSW	4	137,482,458 (GRCm39)	missense	probably benign	0.00
R2067:Alpl	UTSW	4	137,476,856 (GRCm39)	unclassified	probably benign
R4412:Alpl	UTSW	4	137,485,939 (GRCm39)	missense	possibly damaging	0.84
R4440:Alpl	UTSW	4	137,475,124 (GRCm39)	missense	probably damaging	1.00
R5275:Alpl	UTSW	4	137,476,919 (GRCm39)	missense	probably benign	0.00
R5295:Alpl	UTSW	4	137,476,919 (GRCm39)	missense	probably benign	0.00
R5529:Alpl	UTSW	4	137,473,733 (GRCm39)	missense	probably damaging	0.99
R6706:Alpl	UTSW	4	137,473,740 (GRCm39)	missense	probably benign	0.00
R7291:Alpl	UTSW	4	137,480,009 (GRCm39)	missense	probably damaging	1.00
R7693:Alpl	UTSW	4	137,471,120 (GRCm39)	missense	probably damaging	1.00
R7694:Alpl	UTSW	4	137,471,120 (GRCm39)	missense	probably damaging	1.00
R8247:Alpl	UTSW	4	137,473,764 (GRCm39)	missense	probably damaging	1.00
R8725:Alpl	UTSW	4	137,475,127 (GRCm39)	missense	probably benign
R8727:Alpl	UTSW	4	137,475,127 (GRCm39)	missense	probably benign
X0017:Alpl	UTSW	4	137,473,778 (GRCm39)	missense	probably damaging	1.00
Z1176:Alpl	UTSW	4	137,481,321 (GRCm39)	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