Mutagenetix > Incidental Mutation

Incidental Mutation 'R2067:Alpl'

226747

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

040072-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2067 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

137469044-137523695 bp(-) (GRCm39)

Type of Mutation

unclassified

DNA Base Change (assembly)

T to C at 137476856 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000116308 (fasta)

Gene Model

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

AlphaFold

P09242

Predicted Effect

probably benign
Transcript: ENSMUST00000030551

SMART Domains

Protein: ENSMUSP00000030551
Gene: ENSMUSG00000028766

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: ENSMUST00000139951

SMART Domains

Protein: ENSMUSP00000125041
Gene: ENSMUSG00000028766

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000141451

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

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.5%
20x: 95.7%

Validation Efficiency

97% (76/78)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9530002B09Rik	T	A	4: 122,583,115 (GRCm39)		probably benign	Het
Abca2	A	T	2: 25,327,517 (GRCm39)	I669F	possibly damaging	Het
Acin1	T	A	14: 54,902,711 (GRCm39)	Q360H	probably damaging	Het
Aldh3b1	T	A	19: 3,971,755 (GRCm39)	D72V	probably benign	Het
Alox12e	G	A	11: 70,206,828 (GRCm39)	R620W	probably damaging	Het
Amy2a1	T	C	3: 113,324,217 (GRCm39)	I108V	probably benign	Het
Ascc2	A	T	11: 4,631,496 (GRCm39)	M646L	probably benign	Het
Bod1l	G	A	5: 41,974,429 (GRCm39)	T2295M	probably benign	Het
Ccdc9	A	T	7: 16,012,475 (GRCm39)		probably null	Het
Clptm1l	C	T	13: 73,755,842 (GRCm39)	Q153*	probably null	Het
Csmd1	A	G	8: 15,950,782 (GRCm39)	S3476P	probably benign	Het
Ddias	A	T	7: 92,508,907 (GRCm39)	M336K	possibly damaging	Het
Ehd1	T	C	19: 6,348,108 (GRCm39)	L362P	probably benign	Het
Epha1	G	T	6: 42,342,987 (GRCm39)	H187Q	probably benign	Het
Espl1	T	C	15: 102,207,525 (GRCm39)	S330P	probably damaging	Het
Fbln7	G	T	2: 128,719,386 (GRCm39)	R61L	probably damaging	Het
Fbxo41	C	T	6: 85,455,453 (GRCm39)	W577*	probably null	Het
Fgb	C	A	3: 82,956,996 (GRCm39)	D25Y	probably benign	Het
Gc	T	A	5: 89,594,376 (GRCm39)	K37N	probably damaging	Het
Gfpt1	T	C	6: 87,034,736 (GRCm39)	I178T	probably benign	Het
Gm12695	T	C	4: 96,657,963 (GRCm39)	T69A	probably benign	Het
Gm3944	C	A	12: 18,903,895 (GRCm39)	S8*	probably null	Het
Gm9912	T	C	3: 148,890,795 (GRCm39)	T113A	unknown	Het
Gpr156	A	G	16: 37,799,113 (GRCm39)	D109G	probably benign	Het
Hoxd1	A	T	2: 74,593,710 (GRCm39)	T89S	probably benign	Het
Htt	C	T	5: 34,983,326 (GRCm39)	T975I	probably benign	Het
Itpr3	G	A	17: 27,317,050 (GRCm39)	M768I	probably benign	Het
Krt4	C	A	15: 101,833,099 (GRCm39)	A3S	possibly damaging	Het
Mrto4	T	C	4: 139,076,334 (GRCm39)	K86E	probably benign	Het
Mup4	T	A	4: 59,960,622 (GRCm39)		probably benign	Het
Myh1	G	A	11: 67,105,446 (GRCm39)	D1079N	possibly damaging	Het
Myo1a	A	G	10: 127,541,347 (GRCm39)	N43D	probably benign	Het
Napa	A	T	7: 15,849,203 (GRCm39)		probably benign	Het
Ndufa12	A	G	10: 94,056,569 (GRCm39)	D99G	probably damaging	Het
Neb	A	G	2: 52,174,275 (GRCm39)	I1528T	probably benign	Het
Nek1	T	C	8: 61,460,196 (GRCm39)	S41P	probably damaging	Het
Nolc1	C	T	19: 46,072,046 (GRCm39)	T612M	probably damaging	Het
Nsun5	T	G	5: 135,403,926 (GRCm39)	Y301D	probably damaging	Het
Oas1g	T	C	5: 121,023,946 (GRCm39)	E121G	probably damaging	Het
Or1e1f	A	G	11: 73,855,740 (GRCm39)	Y102C	probably damaging	Het
Or2ab1	A	G	11: 58,488,396 (GRCm39)	N58S	probably damaging	Het
Or5d41	A	G	2: 88,054,818 (GRCm39)	V186A	possibly damaging	Het
Or6ae1	T	A	7: 139,742,822 (GRCm39)	I14F	possibly damaging	Het
Or8b46	T	A	9: 38,450,576 (GRCm39)	N128K	probably benign	Het
Or8k38	G	T	2: 86,488,781 (GRCm39)	T7K	probably damaging	Het
Osmr	T	C	15: 6,844,896 (GRCm39)	N957D	probably benign	Het
Parn	G	A	16: 13,420,933 (GRCm39)	S473L	probably damaging	Het
Phc2	T	C	4: 128,640,929 (GRCm39)	F672S	probably damaging	Het
Pik3c2b	T	C	1: 133,027,349 (GRCm39)	S1283P	probably damaging	Het
Pole2	G	A	12: 69,274,926 (GRCm39)	R5W	probably benign	Het
Prl7a2	T	A	13: 27,844,870 (GRCm39)	Y172F	probably damaging	Het
Ptprz1	A	G	6: 23,050,388 (GRCm39)		probably benign	Het
Rapgef3	C	A	15: 97,664,842 (GRCm39)	G7V	probably damaging	Het
Ripor1	T	A	8: 106,344,340 (GRCm39)	S491R	probably benign	Het
Rnf141	A	G	7: 110,420,572 (GRCm39)		probably benign	Het
Ryr3	C	T	2: 112,777,302 (GRCm39)	R285Q	probably damaging	Het
Sall4	T	C	2: 168,598,465 (GRCm39)	N125S	probably benign	Het
Schip1	A	G	3: 68,525,119 (GRCm39)	K360R	probably damaging	Het
Senp6	T	A	9: 79,997,151 (GRCm39)	V55E	probably benign	Het
Skint1	T	A	4: 111,882,730 (GRCm39)	V258D	probably benign	Het
Slc25a16	T	A	10: 62,768,530 (GRCm39)	H130Q	probably benign	Het
Styx	T	C	14: 45,611,020 (GRCm39)	V217A	probably benign	Het
Syne2	G	A	12: 75,935,116 (GRCm39)		probably null	Het
Tagap1	A	G	17: 7,224,259 (GRCm39)	S146P	probably benign	Het
Tatdn2	A	G	6: 113,681,103 (GRCm39)	K379E	probably benign	Het
Thrap3	T	C	4: 126,069,189 (GRCm39)	Y654C	possibly damaging	Het
Tle2	T	C	10: 81,416,385 (GRCm39)	L135P	probably damaging	Het
Tmc1	A	G	19: 20,801,673 (GRCm39)	F451S	possibly damaging	Het
Trpm7	G	A	2: 126,639,647 (GRCm39)	P1650S	probably damaging	Het
Ttll4	G	A	1: 74,719,541 (GRCm39)	R16H	possibly damaging	Het
Ttn	T	C	2: 76,544,717 (GRCm39)	N32795S	probably damaging	Het
Tubgcp6	T	C	15: 88,988,692 (GRCm39)	E803G	probably benign	Het
Ubr2	A	G	17: 47,274,071 (GRCm39)		probably null	Het
Ugt2b35	A	G	5: 87,149,412 (GRCm39)	D221G	probably damaging	Het
Unc45b	G	A	11: 82,802,515 (GRCm39)	A4T	probably benign	Het
Vmn1r70	A	T	7: 10,368,264 (GRCm39)	I251F	possibly damaging	Het
Vmn2r120	T	A	17: 57,831,553 (GRCm39)	H412L	possibly damaging	Het
Zfp59	A	G	7: 27,552,935 (GRCm39)	N129S	probably benign	Het
Zgrf1	T	C	3: 127,406,999 (GRCm39)	C1589R	probably damaging	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
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
R8686:Alpl	UTSW	4	137,471,112 (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'- CACACGACATTCCCTGTGTC -3'
(R):5'- TAGAACCCTGGGTGTGATGG -3'

Sequencing Primer
(F):5'- ATCCAGGTGACTCCCTGAC -3'
(R):5'- GATGGCTCCTTTGTCCCTCAGG -3'

Posted On

2014-09-17