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

TNAP, Akp-2, ALP, TNSALP, Akp2

MMRRC Submission

045322-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7291 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

137469044-137523695 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 137480009 bp (GRCm39)

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: 34,355,699 (GRCm39)	E51G	possibly damaging	Het
Abca14	C	A	7: 119,888,832 (GRCm39)	C1259*	probably null	Het
Ablim1	T	C	19: 57,204,340 (GRCm39)	E17G	probably benign	Het
Acsf3	G	A	8: 123,540,316 (GRCm39)	V505I	probably benign	Het
Actn1	T	C	12: 80,220,859 (GRCm39)	M650V	probably benign	Het
Adamts4	G	A	1: 171,084,097 (GRCm39)	V525I	probably benign	Het
Adh1	T	C	3: 137,988,569 (GRCm39)	Y181H	probably damaging	Het
Ate1	T	G	7: 130,121,661 (GRCm39)	K11Q	probably benign	Het
Atpaf1	T	A	4: 115,668,288 (GRCm39)	F314L	probably damaging	Het
Baiap3	T	A	17: 25,463,291 (GRCm39)	D1004V	probably damaging	Het
Bpifb9a	C	T	2: 154,109,616 (GRCm39)	T504M	probably damaging	Het
C1s2	T	A	6: 124,602,343 (GRCm39)	I623F	probably benign	Het
Card11	T	C	5: 140,886,825 (GRCm39)	D308G	probably damaging	Het
Cul9	C	T	17: 46,851,359 (GRCm39)	V354I	probably benign	Het
Dnah1	A	T	14: 31,020,662 (GRCm39)	F1236I	probably damaging	Het
Dync2h1	T	A	9: 6,929,590 (GRCm39)	I4266F	possibly damaging	Het
Ear10	A	T	14: 44,160,377 (GRCm39)	V150D	probably damaging	Het
Elfn2	C	T	15: 78,557,183 (GRCm39)	A455T	probably benign	Het
Erp44	A	G	4: 48,208,792 (GRCm39)	Y223H	probably damaging	Het
Fam110b	T	A	4: 5,798,895 (GRCm39)	H104Q	probably benign	Het
Fcgbp	A	G	7: 27,800,817 (GRCm39)	N1288D	probably benign	Het
Fcgbpl1	A	C	7: 27,839,645 (GRCm39)	D486A	probably benign	Het
Fcrl1	T	C	3: 87,293,088 (GRCm39)		probably null	Het
Fmo2	G	T	1: 162,715,271 (GRCm39)	P117Q	probably benign	Het
Fsip2	A	G	2: 82,810,863 (GRCm39)	K2394R	possibly damaging	Het
Gab1	T	G	8: 81,526,780 (GRCm39)	K106T	probably damaging	Het
Gatad2b	T	C	3: 90,258,721 (GRCm39)	V248A	probably damaging	Het
Gemin6	T	C	17: 80,535,204 (GRCm39)	S55P	possibly damaging	Het
Gfm2	G	A	13: 97,311,532 (GRCm39)	V701I	probably benign	Het
Gm3250	T	C	10: 77,618,061 (GRCm39)	T106A	unknown	Het
Gm7356	T	C	17: 14,221,843 (GRCm39)	N62S	probably benign	Het
Gsdmc4	T	C	15: 63,774,689 (GRCm39)	T31A	possibly damaging	Het
H2-M10.1	T	A	17: 36,636,621 (GRCm39)	D61V	probably damaging	Het
Heatr5a	A	G	12: 51,972,122 (GRCm39)	L716S	probably damaging	Het
Hecw2	A	G	1: 53,953,753 (GRCm39)	Y831H	probably damaging	Het
Ifi202b	C	T	1: 173,802,381 (GRCm39)	S151N	probably benign	Het
Il15ra	C	T	2: 11,723,192 (GRCm39)	T72I	probably damaging	Het
Ints1	A	G	5: 139,750,829 (GRCm39)	L858P	probably damaging	Het
Kat2a	C	T	11: 100,601,726 (GRCm39)	V230I	possibly damaging	Het
Kcnq2	A	T	2: 180,730,172 (GRCm39)	I498N	possibly damaging	Het
Kif26b	C	T	1: 178,506,611 (GRCm39)	T229I	possibly damaging	Het
Ly75	T	A	2: 60,160,337 (GRCm39)	I957F	probably damaging	Het
Map3k12	T	A	15: 102,410,601 (GRCm39)	R459W	probably damaging	Het
Mia2	T	A	12: 59,205,155 (GRCm39)		probably null	Het
Mrgprf	A	G	7: 144,861,206 (GRCm39)	I53V	unknown	Het
Mttp	A	G	3: 137,796,964 (GRCm39)	L846P	probably damaging	Het
Myrip	C	T	9: 120,246,207 (GRCm39)	L112F	probably damaging	Het
Nav1	A	G	1: 135,393,597 (GRCm39)	F1047S	probably damaging	Het
Nfkbib	T	C	7: 28,458,628 (GRCm39)	D327G	possibly damaging	Het
Notch1	C	T	2: 26,366,387 (GRCm39)	V776I	probably benign	Het
Obsl1	G	T	1: 75,466,161 (GRCm39)	D1522E	probably damaging	Het
Or52s6	T	A	7: 103,091,995 (GRCm39)	M112L	probably benign	Het
Or5b110-ps1	A	T	19: 13,259,517 (GRCm39)	F302I	unknown	Het
Or7e168	T	C	9: 19,719,944 (GRCm39)	M110T	possibly damaging	Het
Or9r3	T	C	10: 129,948,093 (GRCm39)	K189E	probably benign	Het
Pde7a	T	C	3: 19,281,838 (GRCm39)	N471D	probably benign	Het
Pla2r1	T	C	2: 60,360,779 (GRCm39)	H203R	probably benign	Het
Plch2	C	A	4: 155,082,929 (GRCm39)	C573F	probably damaging	Het
Polr1a	G	A	6: 71,918,440 (GRCm39)	R666Q	probably benign	Het
Prepl	T	C	17: 85,388,668 (GRCm39)	N145S	probably benign	Het
Psen2	C	T	1: 180,066,521 (GRCm39)	V139M	probably benign	Het
Ptgdr	A	T	14: 45,096,649 (GRCm39)	M21K	possibly damaging	Het
Rapgef6	T	C	11: 54,582,065 (GRCm39)	W1331R	probably benign	Het
Rp1l1	G	A	14: 64,269,747 (GRCm39)	G1778S	probably benign	Het
Rrbp1	A	T	2: 143,811,382 (GRCm39)	M824K	probably benign	Het
Sel1l	T	C	12: 91,815,739 (GRCm39)	T23A	probably benign	Het
Sele	A	G	1: 163,881,437 (GRCm39)	S515G	possibly damaging	Het
Slc22a23	T	C	13: 34,381,822 (GRCm39)	N421D	probably damaging	Het
Slc35f3	T	G	8: 127,121,297 (GRCm39)	L386R	probably benign	Het
Stab2	G	A	10: 86,782,084 (GRCm39)	S699L	probably damaging	Het
Synrg	A	T	11: 83,900,207 (GRCm39)	L726F	probably damaging	Het
Syt3	G	A	7: 44,045,343 (GRCm39)	V528M	probably damaging	Het
Szt2	A	G	4: 118,248,446 (GRCm39)	I655T	probably damaging	Het
Tbr1	T	C	2: 61,642,600 (GRCm39)	S622P	probably damaging	Het
Tex36	C	T	7: 133,188,952 (GRCm39)	G207S	probably benign	Het
Trav5n-4	G	A	14: 53,550,399 (GRCm39)	W13*	probably null	Het
Trdn	A	T	10: 33,313,732 (GRCm39)	E500V	probably null	Het
Ugt2b38	A	T	5: 87,559,754 (GRCm39)	N379K	probably damaging	Het
Unc13d	T	C	11: 115,964,876 (GRCm39)	R248G	possibly damaging	Het
Vmn1r195	C	T	13: 22,462,919 (GRCm39)	L130F	probably damaging	Het
Vmn2r110	T	C	17: 20,794,471 (GRCm39)	I733V	probably benign	Het
Zfp870	T	A	17: 33,102,828 (GRCm39)	N167I	probably damaging	Het
Zmynd10	A	T	9: 107,426,503 (GRCm39)	M179L	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
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'- AATGGGTTGGGAGCTCTTCC -3'
(R):5'- TCATGTAACCTAGGGAAACTGAG -3'

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

Posted On

2019-06-26