Incidental Mutation 'G4846:Cyp3a13'
| ID |
530 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Cyp3a13
|
| Ensembl Gene |
ENSMUSG00000029727 |
| Gene Name |
cytochrome P450, family 3, subfamily a, polypeptide 13 |
| Synonyms |
steroid inducible, IIIAm2 |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
G4846 (G3)
of strain
Worker
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
5 |
| Chromosomal Location |
137891194-137919881 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
C to T
at 137897085 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Glutamic Acid to Lysine
at position 410
(E410K)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000031741
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000031741]
|
| AlphaFold |
Q64464 |
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000031741
AA Change: E410K
PolyPhen 2
Score 0.549 (Sensitivity: 0.88; Specificity: 0.91)
|
| SMART Domains |
Protein: ENSMUSP00000031741
Gene: ENSMUSG00000029727
AA Change: E410K
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
14 |
24 |
N/A |
INTRINSIC |
|
Pfam:p450
|
38 |
493 |
1.3e-130 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000121449
|
| Meta Mutation Damage Score |
0.3285 |
| Coding Region Coverage |
|
| Het Detection Efficiency |
29.1% |
| Validation Efficiency |
90% (104/115) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the cytochrome P450 superfamily of enzymes, which participate in drug metabolism and the synthesis of cholesterol, steroids and other lipids. This enzyme hydroxylates testosterone and dehydroepiandrosterone 3-sulphate, which is involved in the formation of estriol during pregnancy. This gene is part of a cluster of related genes on chromosome 7q21.1. Naturally-occurring readthrough transcription occurs between this gene and the downstream CYP3A51P pseudogene and is represented by GeneID:100861540. [provided by RefSeq, Jan 2015]
PHENOTYPE: Mice homozygous for a knock-out allele show no apparent alterations in hematology, plasma clinical chemistry or pathology. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(6) : Targeted, knock-out(1) Targeted, other(2) Gene trapped(3) |
| Other mutations in this stock |
Total: 11 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2700049A03Rik |
A |
G |
12: 71,184,683 (GRCm39) |
I24V |
probably benign |
Het |
| Col4a2 |
T |
C |
8: 11,458,872 (GRCm39) |
|
probably benign |
Homo |
| Gm20518 |
A |
T |
16: 17,654,509 (GRCm39) |
|
probably benign |
Homo |
| Nbea |
T |
A |
3: 55,994,918 (GRCm39) |
D166V |
probably damaging |
Het |
| Or5au1 |
T |
A |
14: 52,273,434 (GRCm39) |
M45L |
probably benign |
Het |
| Or6c88 |
A |
T |
10: 129,407,039 (GRCm39) |
I172F |
probably damaging |
Het |
| Plxna4 |
T |
A |
6: 32,169,207 (GRCm39) |
D1330V |
probably damaging |
Het |
| Ppl |
A |
G |
16: 4,905,070 (GRCm39) |
S1742P |
probably damaging |
Homo |
| Samd4 |
T |
A |
14: 47,253,776 (GRCm39) |
I80N |
probably damaging |
Het |
| Spinkl |
T |
A |
18: 44,302,173 (GRCm39) |
|
probably benign |
Het |
| Ttll5 |
T |
A |
12: 86,071,018 (GRCm39) |
I1297N |
probably damaging |
Het |
|
| Other mutations in Cyp3a13 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00501:Cyp3a13
|
APN |
5 |
137,910,195 (GRCm39) |
missense |
probably benign |
0.08 |
|
IGL01879:Cyp3a13
|
APN |
5 |
137,917,265 (GRCm39) |
missense |
probably benign |
|
|
IGL01886:Cyp3a13
|
APN |
5 |
137,897,082 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02048:Cyp3a13
|
APN |
5 |
137,917,257 (GRCm39) |
splice site |
probably benign |
|
|
IGL02102:Cyp3a13
|
APN |
5 |
137,909,865 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL02285:Cyp3a13
|
APN |
5 |
137,908,229 (GRCm39) |
missense |
probably benign |
0.38 |
|
IGL03213:Cyp3a13
|
APN |
5 |
137,892,529 (GRCm39) |
utr 3 prime |
probably benign |
|
|
IGL03238:Cyp3a13
|
APN |
5 |
137,897,151 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL02988:Cyp3a13
|
UTSW |
5 |
137,897,272 (GRCm39) |
nonsense |
probably null |
|
|
PIT4486001:Cyp3a13
|
UTSW |
5 |
137,908,228 (GRCm39) |
missense |
probably benign |
0.17 |
|
R0319:Cyp3a13
|
UTSW |
5 |
137,897,124 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1024:Cyp3a13
|
UTSW |
5 |
137,892,626 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R1189:Cyp3a13
|
UTSW |
5 |
137,909,892 (GRCm39) |
splice site |
probably null |
|
|
R1464:Cyp3a13
|
UTSW |
5 |
137,903,827 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R1464:Cyp3a13
|
UTSW |
5 |
137,903,827 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R1501:Cyp3a13
|
UTSW |
5 |
137,909,892 (GRCm39) |
splice site |
probably null |
|
|
R1838:Cyp3a13
|
UTSW |
5 |
137,909,894 (GRCm39) |
splice site |
probably null |
|
|
R1956:Cyp3a13
|
UTSW |
5 |
137,908,204 (GRCm39) |
missense |
probably benign |
0.02 |
|
R1981:Cyp3a13
|
UTSW |
5 |
137,910,118 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R2048:Cyp3a13
|
UTSW |
5 |
137,908,237 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R2140:Cyp3a13
|
UTSW |
5 |
137,919,716 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R4844:Cyp3a13
|
UTSW |
5 |
137,915,813 (GRCm39) |
missense |
probably benign |
|
|
R5001:Cyp3a13
|
UTSW |
5 |
137,897,178 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5062:Cyp3a13
|
UTSW |
5 |
137,897,161 (GRCm39) |
missense |
possibly damaging |
0.52 |
|
R5420:Cyp3a13
|
UTSW |
5 |
137,897,243 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5855:Cyp3a13
|
UTSW |
5 |
137,917,318 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R6089:Cyp3a13
|
UTSW |
5 |
137,908,215 (GRCm39) |
missense |
probably benign |
0.07 |
|
R6927:Cyp3a13
|
UTSW |
5 |
137,893,546 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6978:Cyp3a13
|
UTSW |
5 |
137,903,801 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7283:Cyp3a13
|
UTSW |
5 |
137,903,818 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7571:Cyp3a13
|
UTSW |
5 |
137,897,125 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R7781:Cyp3a13
|
UTSW |
5 |
137,897,136 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R8281:Cyp3a13
|
UTSW |
5 |
137,892,559 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8987:Cyp3a13
|
UTSW |
5 |
137,909,849 (GRCm39) |
missense |
probably benign |
|
|
R9154:Cyp3a13
|
UTSW |
5 |
137,919,758 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9765:Cyp3a13
|
UTSW |
5 |
137,909,883 (GRCm39) |
missense |
probably damaging |
0.98 |
|
RF007:Cyp3a13
|
UTSW |
5 |
137,892,525 (GRCm39) |
makesense |
probably null |
|
|
RF020:Cyp3a13
|
UTSW |
5 |
137,892,525 (GRCm39) |
makesense |
probably null |
|
|
X0024:Cyp3a13
|
UTSW |
5 |
137,898,653 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified a G to A transition at position 1335 of the Cyp3a13 transcript in exon 11 of 13 total exons. The mutated nucleotide causes a glutamic acid to lysine substitution at amino acid 4317 for the longest predicted isoform using NCBI record XP_918762. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
| Protein Function and Prediction |
The Cyp3a13 gene encodes a 503 amino acid member of the cytochrome P450 family. Cytochrome P450 3A (CYP3A) enzymes constitute an important detoxification system that contributes to primary metabolism of more than half of all prescribed medications. The protein is localized to the peripheral membrane, the endoplasmic reticulum membrane, and microsomal membranes. The enzyme binds iron at amino acid 444 (Uniprot Q64464). Mice lacking all functional Cyp3a genes are viable, fertile, and without marked physiological abnormalities. However, these mice exhibited increased sensitivity and severely impaired detoxification capacity when exposed to the chemotherapeutic agent docetaxel, suggesting a primary role for Cyp3a in xenobiotic detoxification.
The E410K change is predicted to be benign by the PolyPhen program. |
| Posted On |
2010-11-02 |
Incidental Mutation