COL8A1
protein-codingcollagen type VIII alpha 1 chain, the group of C1q domain containing|Collagens
Gene summary
This gene encodes one of the two alpha chains of type VIII collagen. The gene product is a short chain collagen and a major component of the basement membrane of the corneal endothelium. The type VIII collagen fibril can be either a homo- or a heterotrimer. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Dec 2011]
- C3orf7
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~160.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to COL8A1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020351.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | 6 | |||
| missense | 69 | 3 | 1 | 73 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 69 | 6 | 4 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065084.2 | 2 | MANE Select | |
| Ensembl | ENSP00000498483.1 | 2 | MANE Select | |
| RefSeq | NP_001841.2 | 2 | Standard | |
| Ensembl | ENSP00000261037.3 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| col8a1a | Danio rerio | Structure: notochord outer sheath cell Quality: deformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Assembly of collagen fibrils and other multimeric structures
- Collagen chain trimerization
- Collagen biosynthesis and modifying enzymes
- Collagen formation
- Extracellular matrix organization
Biological Process
- angiogenesis
- cell adhesion
- positive regulation of cell-substrate adhesion
- extracellular matrix organization
- endodermal cell differentiation
Molecular Function
- extracellular matrix structural constituent
- protein binding
- extracellular matrix structural constituent conferring tensile strength
Cellular Component
- extracellular region
- collagen type VIII trimer
- extracellular space
- endoplasmic reticulum lumen
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261037
- Coding exons
- 2
- Length
- 160752
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125748
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.44 | 337 | 420 | 0.802 | 0.0000214 | 4636 |
| Missense (PolyPhen) | 76 | 64.085 | 1.1859 | 711 | ||
| Synonymous | 0.480 | 157 | 165 | 0.952 | 0.00000945 | 1733 |
| Loss of Function | 3.08 | 4 | 18.2 | 0.220 | 9.22e-7 | 236 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000081 | 0.000079 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Macromolecular component of the subendothelium. Major component of the Descemet's membrane (basement membrane) of corneal endothelial cells. Also component of the endothelia of blood vessels. Necessary for migration and proliferation of vascular smooth muscle cells and thus, has a potential role in the maintenance of vessel wall integrity and structure, in particular in atherogenesis. {ECO:0000269|PubMed:11708810}.;
Recessive Scores
- pRec
- 0.173
Intolerance Scores
- LoFtool
- 0.0623
- RVIS EVS
- -1.46
- RVIS percentile EVS
- 3.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.739
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |