F8 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- F8 (HGNC:3546) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- coagulation factor VIII
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- F8C
- Alias symbols
- FVIII, DXS1253E, HEMA
- %HI
- 30.72(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.09(Read more about gnomAD LOEUF score)
- Cytoband
- Xq28
- Genomic Coordinates
-
GRCh37/hg19: chrX:154064067-154250998 NCBI Ensembl UCSC GRCh38/hg38: chrX:154835792-155022723 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000132.4 ENST00000360256.9 (Read more about MANE Select)
- Function
- Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- hemophilia A Monarch
-
PUBMED:
2987704
Gitschier (1985) screened 92 haemophiliacs by southern blot analysis of the F8 gene using the TaqI enzyme. They identified two different stopgain mutations and two microdeletions. A de novo stopgain mutation in exon 24 of F8 (ARG2209TER) was identified by Southern blotting in a male subject (H2) with haemophilia A and no family history of disease. The stopgain mutation was confirmed by amplification and sequencing of exon 24 in this family. A maternally inherited stopgain in exon 26 of F8 (ARG2307TER) was identified in a male subject (H22) and his affected male sibling and occurs 26 amino acids upstream of the termination codon. This variant occurs in the last exon and is not predicted to result in nonsense mediated decay. Two instances of partial deletion of the F8 gene include an ~39.0 kb in-frame deletion of exons 23-25 identified in a male subject (H96), and an exon 26 deletion identified in a second male subject (H51). The breakpoints were estimated by Southern blot analysis and were not sequenced.
-
PUBMED:
23534532
Rossetti (2013) genotyped 260 Argentinian haemophilia A patients using inverse shifting PCR (inversion detection), multiplex PCR (large deletions), and conformation sensitive gel electrophoresis (indels and point mutations). They identified a causative variant in 104/104 patients with severe Haemophilia A. This included 59 patients with a recurrent inversion disrupting F8 with one breakpoint positioned in intron 22 (Inv22), 12 patients with large deletions, 12 patients with nonsense mutations, 18 patients with frameshift variants, and three subjects with missense variants.
-
PUBMED:
23551875
You (2013) analyzed DNA samples from 10 patients with severe haemophilia A who were presumed to carry deletions in the F8 gene due to previous failures to amplify exons by conventional PCR analysis. They used a multiplex fluorescence competitive amplification technique (AccuCopy) to detect copy number, and sequenced deletion breakpoints using PCR. The ten exonic deletions included two exon 1 deletions, three frameshift deletions (exons 2-6, exons 2-12, and exon 15), and five in-frame deletions. A DNA sample was available for the mother of a male patient (5-P) with a 27.7 kb in-frame deletion of exons 4-7, and she was confirmed to be a carrier of the deletion.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.