Mutagenetix > Incidental Mutation

Incidental Mutation 'R7291:Alpl'

566400

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

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7291 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

137741733-137796384 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 137752698 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Tryptophan at position 168 (R168W)

Ref Sequence

ENSEMBL: ENSMUSP00000030551 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030551] [ENSMUST00000133473] [ENSMUST00000139951] [ENSMUST00000153588]

AlphaFold

P09242

Predicted Effect

probably damaging
Transcript: ENSMUST00000030551
AA Change: R168W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000030551
Gene: ENSMUSG00000028766
AA Change: R168W

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

Predicted Effect

probably benign
Transcript: ENSMUST00000133473

SMART Domains

Protein: ENSMUSP00000121548
Gene: ENSMUSG00000028766

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
Pfam:Alk_phosphatase	51	98	5.3e-19	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000139951
AA Change: R168W

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000125041
Gene: ENSMUSG00000028766
AA Change: R168W

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
Pfam:Alk_phosphatase	51	216	5.2e-72	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000153588

SMART Domains

Protein: ENSMUSP00000116308
Gene: ENSMUSG00000028766

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
Pfam:Alk_phosphatase	51	158	2e-44	PFAM

Coding Region Coverage

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

Validation Efficiency

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9430069I07Rik	T	C	15: 34,355,553	E51G	possibly damaging	Het
9530053A07Rik	A	C	7: 28,140,220	D486A	probably benign	Het
Abca14	C	A	7: 120,289,609	C1259*	probably null	Het
Ablim1	T	C	19: 57,215,908	E17G	probably benign	Het
Acsf3	G	A	8: 122,813,577	V505I	probably benign	Het
Actn1	T	C	12: 80,174,085	M650V	probably benign	Het
Adamts4	G	A	1: 171,256,528	V525I	probably benign	Het
Adh1	T	C	3: 138,282,808	Y181H	probably damaging	Het
Ate1	T	G	7: 130,519,931	K11Q	probably benign	Het
Atpaf1	T	A	4: 115,811,091	F314L	probably damaging	Het
Baiap3	T	A	17: 25,244,317	D1004V	probably damaging	Het
Bpifb9a	C	T	2: 154,267,696	T504M	probably damaging	Het
C1s2	T	A	6: 124,625,384	I623F	probably benign	Het
Card11	T	C	5: 140,901,070	D308G	probably damaging	Het
Cul9	C	T	17: 46,540,433	V354I	probably benign	Het
Dnah1	A	T	14: 31,298,705	F1236I	probably damaging	Het
Dync2h1	T	A	9: 6,929,590	I4266F	possibly damaging	Het
Ear10	A	T	14: 43,922,920	V150D	probably damaging	Het
Elfn2	C	T	15: 78,672,983	A455T	probably benign	Het
Erp44	A	G	4: 48,208,792	Y223H	probably damaging	Het
Fam110b	T	A	4: 5,798,895	H104Q	probably benign	Het
Fcgbp	A	G	7: 28,101,392	N1288D	probably benign	Het
Fcrl1	T	C	3: 87,385,781		probably null	Het
Fmo2	G	T	1: 162,887,702	P117Q	probably benign	Het
Fsip2	A	G	2: 82,980,519	K2394R	possibly damaging	Het
Gab1	T	G	8: 80,800,151	K106T	probably damaging	Het
Gatad2b	T	C	3: 90,351,414	V248A	probably damaging	Het
Gemin6	T	C	17: 80,227,775	S55P	possibly damaging	Het
Gfm2	G	A	13: 97,175,024	V701I	probably benign	Het
Gm3250	T	C	10: 77,782,227	T106A	unknown	Het
Gm7356	T	C	17: 14,001,581	N62S	probably benign	Het
Gsdmc4	T	C	15: 63,902,840	T31A	possibly damaging	Het
H2-M10.1	T	A	17: 36,325,729	D61V	probably damaging	Het
Heatr5a	A	G	12: 51,925,339	L716S	probably damaging	Het
Hecw2	A	G	1: 53,914,594	Y831H	probably damaging	Het
Ifi202b	C	T	1: 173,974,815	S151N	probably benign	Het
Il15ra	C	T	2: 11,718,381	T72I	probably damaging	Het
Ints1	A	G	5: 139,765,074	L858P	probably damaging	Het
Kat2a	C	T	11: 100,710,900	V230I	possibly damaging	Het
Kcnq2	A	T	2: 181,088,379	I498N	possibly damaging	Het
Kif26b	C	T	1: 178,679,046	T229I	possibly damaging	Het
Ly75	T	A	2: 60,329,993	I957F	probably damaging	Het
Map3k12	T	A	15: 102,502,166	R459W	probably damaging	Het
Mia2	T	A	12: 59,158,369		probably null	Het
Mrgprf	A	G	7: 145,307,469	I53V	unknown	Het
Mttp	A	G	3: 138,091,203	L846P	probably damaging	Het
Myrip	C	T	9: 120,417,141	L112F	probably damaging	Het
Nav1	A	G	1: 135,465,859	F1047S	probably damaging	Het
Nfkbib	T	C	7: 28,759,203	D327G	possibly damaging	Het
Notch1	C	T	2: 26,476,375	V776I	probably benign	Het
Obsl1	G	T	1: 75,489,517	D1522E	probably damaging	Het
Olfr1464-ps1	A	T	19: 13,282,153	F302I	unknown	Het
Olfr605	T	A	7: 103,442,788	M112L	probably benign	Het
Olfr823	T	C	10: 130,112,224	K189E	probably benign	Het
Olfr859	T	C	9: 19,808,648	M110T	possibly damaging	Het
Pde7a	T	C	3: 19,227,674	N471D	probably benign	Het
Pla2r1	T	C	2: 60,530,435	H203R	probably benign	Het
Plch2	C	A	4: 154,998,472	C573F	probably damaging	Het
Polr1a	G	A	6: 71,941,456	R666Q	probably benign	Het
Prepl	T	C	17: 85,081,240	N145S	probably benign	Het
Psen2	C	T	1: 180,238,956	V139M	probably benign	Het
Ptgdr	A	T	14: 44,859,192	M21K	possibly damaging	Het
Rapgef6	T	C	11: 54,691,239	W1331R	probably benign	Het
Rp1l1	G	A	14: 64,032,298	G1778S	probably benign	Het
Rrbp1	A	T	2: 143,969,462	M824K	probably benign	Het
Sel1l	T	C	12: 91,848,965	T23A	probably benign	Het
Sele	A	G	1: 164,053,868	S515G	possibly damaging	Het
Slc22a23	T	C	13: 34,197,839	N421D	probably damaging	Het
Slc35f3	T	G	8: 126,394,558	L386R	probably benign	Het
Stab2	G	A	10: 86,946,220	S699L	probably damaging	Het
Synrg	A	T	11: 84,009,381	L726F	probably damaging	Het
Syt3	G	A	7: 44,395,919	V528M	probably damaging	Het
Szt2	A	G	4: 118,391,249	I655T	probably damaging	Het
Tbr1	T	C	2: 61,812,256	S622P	probably damaging	Het
Tex36	C	T	7: 133,587,223	G207S	probably benign	Het
Trav5n-4	G	A	14: 53,312,942	W13*	probably null	Het
Trdn	A	T	10: 33,437,736	E500V	probably null	Het
Ugt2b38	A	T	5: 87,411,895	N379K	probably damaging	Het
Unc13d	T	C	11: 116,074,050	R248G	possibly damaging	Het
Vmn1r195	C	T	13: 22,278,749	L130F	probably damaging	Het
Vmn2r110	T	C	17: 20,574,209	I733V	probably benign	Het
Zfp870	T	A	17: 32,883,854	N167I	probably damaging	Het
Zmynd10	A	T	9: 107,549,304	M179L	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
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
R8686:Alpl	UTSW	4	137743801	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'- AATGGGTTGGGAGCTCTTCC -3'
(R):5'- TCATGTAACCTAGGGAAACTGAG -3'

Sequencing Primer
(F):5'- TTCCTAGGCCACCCTGG -3'
(R):5'- AGGCCCAGGCAACCAGAG -3'

Posted On

2019-06-26