Incidental Mutation 'F6893:F13a1'
| ID |
186 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
F13a1
|
| Ensembl Gene |
ENSMUSG00000039109 |
| Gene Name |
coagulation factor XIII, A1 subunit |
| Synonyms |
Factor XIIIA, 1200014I03Rik |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
F6893 (G3)
of strain
busy
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
13 |
| Chromosomal Location |
37051152-37234220 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 37155999 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Histidine
at position 205
(Y205H)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000128316
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000037491]
[ENSMUST00000164727]
|
| AlphaFold |
Q8BH61 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000037491
AA Change: Y205H
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000048667
Gene: ENSMUSG00000039109
AA Change: Y205H
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Transglut_N
|
47 |
165 |
9e-34 |
PFAM |
|
TGc
|
307 |
400 |
2.01e-45 |
SMART |
|
Pfam:Transglut_C
|
519 |
623 |
2e-26 |
PFAM |
|
Pfam:Transglut_C
|
631 |
728 |
1.3e-21 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000164727
AA Change: Y205H
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000128316
Gene: ENSMUSG00000039109
AA Change: Y205H
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Transglut_N
|
46 |
167 |
3e-38 |
PFAM |
|
TGc
|
307 |
400 |
2.01e-45 |
SMART |
|
Pfam:Transglut_C
|
519 |
623 |
2.2e-23 |
PFAM |
|
Pfam:Transglut_C
|
631 |
728 |
1.1e-22 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000224446
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000224527
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000224783
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000225168
|
| Meta Mutation Damage Score |
0.4737 |
| Coding Region Coverage |
|
| Validation Efficiency |
88% (165/188) |
| MGI Phenotype |
FUNCTION: This gene encodes subunit A of the coagulation factor XIII that catalyzes the final step of the blood coagulation pathway. The encoded protein associates with subunit B to form a heterotetrameric proenzyme that undergoes thrombin-mediated proteolysis to generate active factor XIIIa. The transglutaminase activity of factor XIIIa is required for the calcium-dependent crosslinking of fibrin, leading to the formation of a clot. Mice lacking the encoded protein display impaired reproduction and reduced survival due to bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage. Additionally, mice lacking the encoded protein exhibit impaired wound healing and inadequate healing of myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
PHENOTYPE: Homozygous mutant mice exhibit bleeding symptoms, increased lethality, and impaired fertility. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(2) : Targeted, knock-out(2) |
| Other mutations in this stock |
Total: 35 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca14 |
G |
A |
7: 119,924,261 (GRCm39) |
V1638M |
probably damaging |
Het |
| Agrn |
C |
T |
4: 156,258,636 (GRCm39) |
R972Q |
probably benign |
Het |
| Anxa3 |
T |
C |
5: 96,972,853 (GRCm39) |
|
probably benign |
Het |
| Bpifa6 |
G |
T |
2: 153,829,078 (GRCm39) |
D202Y |
probably damaging |
Het |
| Ccdc15 |
G |
A |
9: 37,226,936 (GRCm39) |
T346I |
probably damaging |
Homo |
| Celsr3 |
G |
A |
9: 108,712,266 (GRCm39) |
R1731H |
probably benign |
Het |
| Ces4a |
A |
G |
8: 105,873,859 (GRCm39) |
R443G |
possibly damaging |
Het |
| Chd2 |
T |
C |
7: 73,157,620 (GRCm39) |
Q175R |
possibly damaging |
Het |
| Dpyd |
T |
A |
3: 118,597,783 (GRCm39) |
|
probably null |
Het |
| Dscam |
G |
T |
16: 96,857,660 (GRCm39) |
H117N |
possibly damaging |
Het |
| Fat3 |
A |
C |
9: 15,918,085 (GRCm39) |
L1446R |
probably damaging |
Homo |
| Golga4 |
T |
C |
9: 118,382,525 (GRCm39) |
L515S |
probably damaging |
Het |
| Hoxb1 |
A |
T |
11: 96,256,728 (GRCm39) |
T26S |
probably benign |
Het |
| Igsf10 |
T |
G |
3: 59,238,481 (GRCm39) |
T567P |
probably damaging |
Het |
| Lamb2 |
T |
C |
9: 108,359,755 (GRCm39) |
V365A |
probably benign |
Het |
| Mepe |
A |
G |
5: 104,485,242 (GRCm39) |
I127M |
possibly damaging |
Het |
| Mpi |
A |
T |
9: 57,453,832 (GRCm39) |
M230K |
probably benign |
Homo |
| Myh4 |
A |
G |
11: 67,146,283 (GRCm39) |
D1447G |
probably null |
Homo |
| Or1f19 |
A |
G |
16: 3,411,027 (GRCm39) |
I256V |
possibly damaging |
Het |
| Or1j4 |
A |
G |
2: 36,740,819 (GRCm39) |
T254A |
probably benign |
Het |
| Panx2 |
T |
C |
15: 88,952,213 (GRCm39) |
Y227H |
probably damaging |
Homo |
| Pdzd7 |
A |
G |
19: 45,025,173 (GRCm39) |
W441R |
probably damaging |
Het |
| Poldip2 |
A |
G |
11: 78,410,020 (GRCm39) |
I267M |
probably damaging |
Homo |
| Pros1 |
T |
A |
16: 62,745,002 (GRCm39) |
V539E |
probably damaging |
Het |
| Sacs |
T |
C |
14: 61,450,425 (GRCm39) |
M4157T |
probably benign |
Het |
| Slc45a3 |
A |
G |
1: 131,909,075 (GRCm39) |
E424G |
probably benign |
Homo |
| Slc9a1 |
A |
G |
4: 133,149,457 (GRCm39) |
E761G |
probably benign |
Homo |
| Stab2 |
G |
A |
10: 86,691,035 (GRCm39) |
P2178L |
probably damaging |
Het |
| Syt4 |
C |
T |
18: 31,577,274 (GRCm39) |
V27I |
possibly damaging |
Homo |
| Thumpd1 |
T |
A |
7: 119,319,799 (GRCm39) |
K56* |
probably null |
Het |
| Tpr |
A |
G |
1: 150,269,313 (GRCm39) |
K19E |
possibly damaging |
Homo |
| Ttll10 |
A |
G |
4: 156,132,775 (GRCm39) |
I74T |
probably benign |
Het |
| Txnrd1 |
C |
T |
10: 82,702,823 (GRCm39) |
Q95* |
probably null |
Homo |
| Zc3h7b |
A |
G |
15: 81,662,872 (GRCm39) |
E421G |
possibly damaging |
Homo |
| Zc3hc1 |
G |
T |
6: 30,387,525 (GRCm39) |
D51E |
probably benign |
Homo |
|
| Other mutations in F13a1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01304:F13a1
|
APN |
13 |
37,172,852 (GRCm39) |
missense |
probably benign |
0.11 |
|
IGL01444:F13a1
|
APN |
13 |
37,102,551 (GRCm39) |
missense |
probably null |
1.00 |
|
IGL02188:F13a1
|
APN |
13 |
37,090,035 (GRCm39) |
splice site |
probably benign |
|
|
IGL02591:F13a1
|
APN |
13 |
37,082,031 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02660:F13a1
|
APN |
13 |
37,127,868 (GRCm39) |
missense |
possibly damaging |
0.92 |
|
IGL03244:F13a1
|
APN |
13 |
37,172,870 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
IGL03401:F13a1
|
APN |
13 |
37,082,054 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0082:F13a1
|
UTSW |
13 |
37,172,927 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R0657:F13a1
|
UTSW |
13 |
37,152,079 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R1225:F13a1
|
UTSW |
13 |
37,209,825 (GRCm39) |
missense |
probably benign |
|
|
R1430:F13a1
|
UTSW |
13 |
37,082,105 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1608:F13a1
|
UTSW |
13 |
37,052,785 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1883:F13a1
|
UTSW |
13 |
37,172,981 (GRCm39) |
missense |
probably benign |
0.01 |
|
R2115:F13a1
|
UTSW |
13 |
37,172,831 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2121:F13a1
|
UTSW |
13 |
37,209,653 (GRCm39) |
missense |
probably benign |
0.01 |
|
R2122:F13a1
|
UTSW |
13 |
37,209,653 (GRCm39) |
missense |
probably benign |
0.01 |
|
R2125:F13a1
|
UTSW |
13 |
37,076,815 (GRCm39) |
missense |
probably benign |
0.15 |
|
R2392:F13a1
|
UTSW |
13 |
37,127,971 (GRCm39) |
missense |
possibly damaging |
0.65 |
|
R3618:F13a1
|
UTSW |
13 |
37,127,967 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3625:F13a1
|
UTSW |
13 |
37,082,067 (GRCm39) |
missense |
probably benign |
0.31 |
|
R3772:F13a1
|
UTSW |
13 |
37,082,108 (GRCm39) |
missense |
probably benign |
|
|
R3838:F13a1
|
UTSW |
13 |
37,231,398 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R3857:F13a1
|
UTSW |
13 |
37,209,668 (GRCm39) |
missense |
probably benign |
0.32 |
|
R3937:F13a1
|
UTSW |
13 |
37,100,875 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4934:F13a1
|
UTSW |
13 |
37,061,736 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4974:F13a1
|
UTSW |
13 |
37,100,837 (GRCm39) |
critical splice donor site |
probably null |
|
|
R5033:F13a1
|
UTSW |
13 |
37,172,830 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5194:F13a1
|
UTSW |
13 |
37,156,037 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5740:F13a1
|
UTSW |
13 |
37,082,178 (GRCm39) |
missense |
probably benign |
0.02 |
|
R5753:F13a1
|
UTSW |
13 |
37,082,082 (GRCm39) |
nonsense |
probably null |
|
|
R6188:F13a1
|
UTSW |
13 |
37,209,752 (GRCm39) |
missense |
probably benign |
0.12 |
|
R7048:F13a1
|
UTSW |
13 |
37,082,117 (GRCm39) |
missense |
probably benign |
0.02 |
|
R7197:F13a1
|
UTSW |
13 |
37,100,860 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7816:F13a1
|
UTSW |
13 |
37,209,745 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7843:F13a1
|
UTSW |
13 |
37,209,745 (GRCm39) |
missense |
probably benign |
0.00 |
|
R7902:F13a1
|
UTSW |
13 |
37,172,913 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8124:F13a1
|
UTSW |
13 |
37,209,779 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8443:F13a1
|
UTSW |
13 |
37,209,692 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8856:F13a1
|
UTSW |
13 |
37,100,859 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8864:F13a1
|
UTSW |
13 |
37,061,753 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9026:F13a1
|
UTSW |
13 |
37,102,506 (GRCm39) |
missense |
probably null |
1.00 |
|
R9092:F13a1
|
UTSW |
13 |
37,089,993 (GRCm39) |
missense |
probably benign |
0.17 |
|
R9268:F13a1
|
UTSW |
13 |
37,076,910 (GRCm39) |
missense |
probably benign |
0.00 |
|
R9274:F13a1
|
UTSW |
13 |
37,052,761 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9497:F13a1
|
UTSW |
13 |
37,082,118 (GRCm39) |
missense |
probably benign |
0.05 |
|
R9645:F13a1
|
UTSW |
13 |
37,082,154 (GRCm39) |
missense |
probably benign |
|
|
Z1088:F13a1
|
UTSW |
13 |
37,172,986 (GRCm39) |
nonsense |
probably null |
|
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified a T to C transition at position 706 of the F13a1 transcript in exon 6 of 16 total exons. The mutated nucleotide causes a tyrosine to histidine substitution at amino acid 205 of the encoded protein. Three transcripts of the F13a1 gene are displayed on Ensembl. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
| Protein Function and Prediction |
The F13a1 gene encodes a putative 732 amino acid protein that is a subunit of Factor XIII and is necessary for wound healing and clot development (Uniprot Q8BH61). Homozygous mutant mice exhibit bleeding symptoms, increased lethality, and impaired fertility. Humans with mutations in this gene display abnormal bleeding (OMIM 134570).
The Y205H change is predicted to be probably damaging by the PolyPhen program. |
| Posted On |
2010-05-03 |
Incidental Mutation