Mutagenetix > Incidental Mutation

Incidental Mutation 'R2013:Alpl'

222328

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

040022-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R2013 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

137469044-137523695 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 137482458 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Histidine to Asparagine at position 79 (H79N)

Ref Sequence

ENSEMBL: ENSMUSP00000121548 (fasta)

Gene Model

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

AlphaFold

P09242

Predicted Effect

probably benign
Transcript: ENSMUST00000030551
AA Change: H79N

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000030551
Gene: ENSMUSG00000028766
AA Change: H79N

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
AA Change: H79N

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000121548
Gene: ENSMUSG00000028766
AA Change: H79N

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133566

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000138463

Predicted Effect

probably benign
Transcript: ENSMUST00000139951
AA Change: H79N

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000125041
Gene: ENSMUSG00000028766
AA Change: H79N

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: ENSMUST00000143757

Predicted Effect

probably benign
Transcript: ENSMUST00000153588
AA Change: H79N

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000116308
Gene: ENSMUSG00000028766
AA Change: H79N

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: 99.1%
3x: 98.5%
10x: 96.8%
20x: 93.7%

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: 80 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700122O11Rik	T	G	17: 48,347,723 (GRCm39)	T194P	possibly damaging	Het
4921504E06Rik	T	A	2: 19,545,124 (GRCm39)	M110L	probably benign	Het
Acad9	T	G	3: 36,127,737 (GRCm39)	I113R	probably damaging	Het
Adam34l	T	C	8: 44,079,442 (GRCm39)	S261G	possibly damaging	Het
Adamts6	A	T	13: 104,450,812 (GRCm39)	I332F	probably damaging	Het
Adcy8	C	T	15: 64,639,727 (GRCm39)	G678S	probably benign	Het
Afg3l2	C	T	18: 67,564,842 (GRCm39)	V211I	probably damaging	Het
Ahnak	T	C	19: 8,991,937 (GRCm39)	I4407T	probably damaging	Het
Apc	A	G	18: 34,448,644 (GRCm39)	I1813V	probably damaging	Het
Ascc3	T	C	10: 50,525,908 (GRCm39)	M540T	probably damaging	Het
Blm	T	C	7: 80,152,147 (GRCm39)	E600G	probably damaging	Het
Btbd8	T	C	5: 107,658,655 (GRCm39)	W1742R	probably damaging	Het
Cadps	T	A	14: 12,522,337 (GRCm38)	D609V	probably damaging	Het
Ccdc69	C	T	11: 54,941,983 (GRCm39)	M174I	probably benign	Het
Cdk13	A	T	13: 17,913,748 (GRCm39)	L877*	probably null	Het
Cdk14	T	C	5: 5,143,047 (GRCm39)	Y228C	probably damaging	Het
Dip2c	C	T	13: 9,617,882 (GRCm39)	Q426*	probably null	Het
Dsp	A	G	13: 38,375,434 (GRCm39)	N1073S	probably damaging	Het
Epyc	T	C	10: 97,511,655 (GRCm39)	I216T	probably damaging	Het
Erbin	A	G	13: 103,994,041 (GRCm39)	S300P	probably damaging	Het
Ercc3	A	G	18: 32,381,482 (GRCm39)	T433A	probably benign	Het
Exoc4	A	G	6: 33,243,026 (GRCm39)	T80A	probably damaging	Het
Foxm1	T	A	6: 128,352,465 (GRCm39)		probably null	Het
Gaa	A	G	11: 119,175,409 (GRCm39)		probably null	Het
H2-Q4	A	G	17: 35,599,526 (GRCm39)	E203G	probably damaging	Het
Helt	T	C	8: 46,745,355 (GRCm39)	D214G	probably damaging	Het
Hlcs	A	G	16: 94,063,599 (GRCm39)	V487A	probably benign	Het
Hmmr	A	T	11: 40,619,259 (GRCm39)	S74T	possibly damaging	Het
Hspa9	A	T	18: 35,079,701 (GRCm39)	Y243N	probably damaging	Het
Htt	T	G	5: 35,010,215 (GRCm39)	L1556R	probably damaging	Het
Ift80	T	C	3: 68,898,117 (GRCm39)	K73E	possibly damaging	Het
Il6st	G	A	13: 112,635,423 (GRCm39)	A551T	probably null	Het
Kdm5a	T	C	6: 120,408,951 (GRCm39)	S1545P	probably benign	Het
Lef1	T	A	3: 130,905,236 (GRCm39)	I39N	probably damaging	Het
Lmo2	T	C	2: 103,811,407 (GRCm39)	Y147H	probably damaging	Het
Lrp6	A	G	6: 134,457,337 (GRCm39)		probably null	Het
Macf1	T	C	4: 123,577,807 (GRCm39)	D59G	probably damaging	Het
Maged1	T	C	X: 93,580,523 (GRCm39)	Y636C	possibly damaging	Het
Mamdc4	T	A	2: 25,453,584 (GRCm39)	D1195V	probably damaging	Het
Mob3b	A	G	4: 35,083,922 (GRCm39)	V89A	probably benign	Het
Mogs	C	T	6: 83,094,631 (GRCm39)	R483*	probably null	Het
Mybphl	A	C	3: 108,282,718 (GRCm39)	T203P	probably benign	Het
Myo15a	A	G	11: 60,385,057 (GRCm39)	T1720A	probably damaging	Het
Myo16	T	A	8: 10,552,796 (GRCm39)	F945I	probably damaging	Het
Nbeal2	G	A	9: 110,463,139 (GRCm39)	L1309F	probably benign	Het
Nes	A	G	3: 87,883,985 (GRCm39)	Q748R	possibly damaging	Het
Nhsl1	A	T	10: 18,387,340 (GRCm39)	R205W	probably damaging	Het
Nlrc3	A	C	16: 3,782,974 (GRCm39)	L161R	probably damaging	Het
Npy2r	T	A	3: 82,448,487 (GRCm39)	D96V	probably damaging	Het
Or4d11	T	A	19: 12,013,518 (GRCm39)	E196V	probably damaging	Het
Or5w18	T	G	2: 87,632,847 (GRCm39)	V38G	probably damaging	Het
Pappa2	C	T	1: 158,662,498 (GRCm39)	C1159Y	probably damaging	Het
Phf21a	T	C	2: 92,058,828 (GRCm39)		probably null	Het
Pik3c2a	T	A	7: 115,950,166 (GRCm39)		probably null	Het
Psg22	A	T	7: 18,453,560 (GRCm39)	Y85F	possibly damaging	Het
Pttg1ip2	T	A	5: 5,505,964 (GRCm39)	I106L	probably benign	Het
Qtrt2	A	G	16: 43,689,455 (GRCm39)	I181T	probably damaging	Het
Sash1	A	T	10: 8,605,177 (GRCm39)	V1071D	probably benign	Het
Scn10a	A	T	9: 119,442,802 (GRCm39)	I1481N	probably damaging	Het
Slc15a1	G	A	14: 121,713,399 (GRCm39)	A376V	possibly damaging	Het
Slc25a46	A	T	18: 31,742,778 (GRCm39)	H29Q	probably benign	Het
Slit2	T	C	5: 48,459,832 (GRCm39)	C1354R	probably damaging	Het
Ssu2	C	T	6: 112,360,902 (GRCm39)	E52K	possibly damaging	Het
Taar7e	A	T	10: 23,913,732 (GRCm39)	H74L	possibly damaging	Het
Tcte1	A	T	17: 45,852,237 (GRCm39)	N490I	probably benign	Het
Tent4b	T	A	8: 88,972,223 (GRCm39)		probably null	Het
Tpst2	G	T	5: 112,455,880 (GRCm39)	G140C	probably damaging	Het
Trip11	A	T	12: 101,803,981 (GRCm39)	F1634I	probably damaging	Het
Trpm2	A	G	10: 77,761,600 (GRCm39)	F1017L	probably damaging	Het
Utp18	A	G	11: 93,766,948 (GRCm39)	V253A	possibly damaging	Het
Vmn2r102	A	G	17: 19,897,006 (GRCm39)	T118A	probably benign	Het
Vmn2r14	T	C	5: 109,369,109 (GRCm39)	T155A	probably benign	Het
Vmn2r19	T	A	6: 123,292,954 (GRCm39)	M332K	probably benign	Het
Vmn2r71	T	A	7: 85,269,845 (GRCm39)	M452K	probably benign	Het
Vmn2r79	T	G	7: 86,653,289 (GRCm39)	L518R	possibly damaging	Het
Vps13b	T	C	15: 35,607,288 (GRCm39)	S1074P	probably damaging	Het
Vps13d	A	G	4: 144,835,078 (GRCm39)	S2757P	probably damaging	Het
Wdr33	C	A	18: 32,022,029 (GRCm39)	Q860K	unknown	Het
Zfp423	T	A	8: 88,509,025 (GRCm39)	I440F	probably benign	Het
Zup1	A	G	10: 33,805,820 (GRCm39)	V437A	possibly 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
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
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'- TGAACTAAATGCTTGGGAATGGC -3'
(R):5'- CCTACCGCCCTGAGAATATG -3'

Sequencing Primer
(F):5'- GGAATGGCTCCTGGTTTCACC -3'
(R):5'- TGCGGCGACATGTCATG -3'

Posted On

2014-08-25