Incidental Mutation 'R4440:Alpl'
| ID |
329712 |
| 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 |
041705-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R4440 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
4 |
| Chromosomal Location |
137469044-137523695 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 137475124 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tryptophan to Arginine
at position 270
(W270R)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000030551
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000030551]
[ENSMUST00000139951]
|
| AlphaFold |
P09242 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000030551
AA Change: W270R
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000030551
Gene: ENSMUSG00000028766
AA Change: W270R
| 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
|
| Meta Mutation Damage Score |
0.9694 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.2%
- 20x: 95.2%
|
| Validation Efficiency |
94% (46/49) |
| 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: 41 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adnp |
G |
T |
2: 168,026,721 (GRCm39) |
H191Q |
possibly damaging |
Het |
| Afdn |
T |
C |
17: 14,071,152 (GRCm39) |
W782R |
probably damaging |
Het |
| Angpt4 |
G |
T |
2: 151,786,566 (GRCm39) |
G508C |
probably damaging |
Het |
| Armc8 |
T |
A |
9: 99,366,087 (GRCm39) |
H609L |
probably benign |
Het |
| Atg2a |
T |
C |
19: 6,305,859 (GRCm39) |
|
probably null |
Het |
| Bicdl2 |
C |
T |
17: 23,886,590 (GRCm39) |
A393V |
probably benign |
Het |
| C6 |
A |
T |
15: 4,764,733 (GRCm39) |
K143M |
possibly damaging |
Het |
| Cfc1 |
T |
A |
1: 34,583,183 (GRCm39) |
|
probably benign |
Het |
| Ctnna3 |
A |
G |
10: 64,096,714 (GRCm39) |
I417M |
probably benign |
Het |
| Dnhd1 |
G |
A |
7: 105,345,935 (GRCm39) |
W2307* |
probably null |
Het |
| Dpysl5 |
T |
C |
5: 30,949,612 (GRCm39) |
F461L |
probably damaging |
Het |
| Fip1l1 |
T |
C |
5: 74,697,446 (GRCm39) |
|
probably benign |
Het |
| Fpgs |
C |
T |
2: 32,577,513 (GRCm39) |
C219Y |
probably damaging |
Het |
| Fsip2 |
A |
G |
2: 82,821,550 (GRCm39) |
D5761G |
possibly damaging |
Het |
| Hdac4 |
C |
A |
1: 91,873,717 (GRCm39) |
G957C |
probably damaging |
Het |
| Klhl8 |
A |
G |
5: 104,015,433 (GRCm39) |
I421T |
probably benign |
Het |
| Kntc1 |
T |
C |
5: 123,932,216 (GRCm39) |
C1337R |
probably damaging |
Het |
| Lpin3 |
A |
G |
2: 160,740,565 (GRCm39) |
N370S |
probably benign |
Het |
| Man2a2 |
C |
A |
7: 80,001,463 (GRCm39) |
R1148L |
probably benign |
Het |
| Mideas |
C |
T |
12: 84,203,245 (GRCm39) |
G886S |
probably benign |
Het |
| Nav2 |
C |
T |
7: 49,201,785 (GRCm39) |
T1453I |
possibly damaging |
Het |
| Nav2 |
A |
G |
7: 49,225,011 (GRCm39) |
|
probably benign |
Het |
| Ndufaf5 |
T |
A |
2: 140,012,645 (GRCm39) |
V5D |
probably benign |
Het |
| Nipbl |
G |
C |
15: 8,396,142 (GRCm39) |
Q144E |
probably damaging |
Het |
| Ntrk2 |
G |
C |
13: 59,208,126 (GRCm39) |
Q657H |
probably damaging |
Het |
| Or4a75 |
G |
T |
2: 89,448,512 (GRCm39) |
T8K |
probably damaging |
Het |
| Or4c107 |
G |
A |
2: 88,789,685 (GRCm39) |
E292K |
probably benign |
Het |
| Polr1a |
A |
G |
6: 71,927,832 (GRCm39) |
D861G |
probably damaging |
Het |
| Pramel15 |
A |
T |
4: 144,099,437 (GRCm39) |
F443I |
probably benign |
Het |
| Pwwp2b |
T |
C |
7: 138,835,555 (GRCm39) |
I332T |
probably benign |
Het |
| Rasgrf2 |
T |
C |
13: 92,131,797 (GRCm39) |
D620G |
possibly damaging |
Het |
| Slc14a2 |
A |
G |
18: 78,238,962 (GRCm39) |
V219A |
probably benign |
Het |
| Slc7a2 |
T |
C |
8: 41,355,686 (GRCm39) |
I245T |
probably benign |
Het |
| Smok3c |
T |
A |
5: 138,062,866 (GRCm39) |
Y118N |
possibly damaging |
Het |
| Taok2 |
C |
T |
7: 126,465,693 (GRCm39) |
R367Q |
possibly damaging |
Het |
| Tbl1xr1 |
A |
G |
3: 22,254,752 (GRCm39) |
|
probably null |
Het |
| Tbr1 |
A |
T |
2: 61,635,182 (GRCm39) |
D44V |
possibly damaging |
Het |
| Tespa1 |
C |
T |
10: 130,197,826 (GRCm39) |
R283C |
probably damaging |
Het |
| Tle2 |
A |
G |
10: 81,417,516 (GRCm39) |
E227G |
possibly damaging |
Het |
| Vmn1r231 |
T |
C |
17: 21,110,718 (GRCm39) |
R66G |
possibly damaging |
Het |
| Xab2 |
T |
C |
8: 3,666,353 (GRCm39) |
E185G |
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 |
|
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'- CCTTCTCCGAACTTGTTGGG -3'
(R):5'- ATCCAACAACCTCTGCATATCTGTC -3'
Sequencing Primer
(F):5'- TATGACAACTGGGGCTCATCTGC -3'
(R):5'- CTGTCATTTCTTGAGTACAGAGATGC -3'
|
| Posted On |
2015-07-21 |
Incidental Mutation