C8G
protein-codingcomplement C8 gamma chain, the group of Complement system activation components|Lipocalins
Gene summary
The protein encoded by this gene belongs to the lipocalin family. It is one of the three subunits that constitutes complement component 8 (C8), which is composed of a disulfide-linked C8 alpha-gamma heterodimer and a non-covalently associated C8 beta chain. C8 participates in the formation of the membrane attack complex (MAC) on bacterial cell membranes. While subunits alpha and beta play a role in complement-mediated bacterial killing, the gamma subunit is not required for the bactericidal activity. [provided by RefSeq, Jul 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.8 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 C8G variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000606.3. 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 | 1 | 12 | 1 | 14 | ||
| missense | 44 | 3 | 1 | 48 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 54 | 16 | 2 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000597.2 | 7 | MANE Select | |
| Ensembl | ENSP00000360697.3 | 7 | MANE Select | |
| Ensembl | ENSP00000497973.1 | 2 | Standard | |
| Ensembl | ENSP00000497839.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prion diseases - Homo sapiens (human)
- Complement and coagulation cascades - Homo sapiens (human)
- Systemic lupus erythematosus - Homo sapiens (human)
- Amoebiasis - Homo sapiens (human)
- Dengue-2 Interactions with Complement and Coagulation Cascades
Biological Process
- complement activation, alternative pathway
- complement activation, classical pathway
- cytolysis
- regulation of complement activation
Molecular Function
- retinol binding
Cellular Component
- extracellular region
- membrane attack complex
- extracellular exosome
- blood microparticle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000224181
- Coding exons
- 7
- Length
- 1729
- Individuals with no LoFs
- 125143
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 245
- Defined
- 125389
- p
- 0.000981
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.364 | 141 | 129 | 1.09 | 0.00000852 | 1260 |
| Missense (PolyPhen) | 30 | 35.498 | 0.84511 | 392 | ||
| Synonymous | -2.49 | 78 | 54.6 | 1.43 | 0.00000360 | 425 |
| Loss of Function | -1.86 | 21 | 13.6 | 1.54 | 8.23e-7 | 122 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00059 | 0.00056 | rare |
| Latino/Admixed American | 0.00074 | 0.00072 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0092 | 0.0091 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00035 | 0.00031 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0.0010 | 0.00098 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: C8 is a constituent of the membrane attack complex. C8 binds to the C5B-7 complex, forming the C5B-8 complex. C5-B8 binds C9 and acts as a catalyst in the polymerization of C9. The gamma subunit seems to be able to bind retinol.;
Intolerance Scores
- LoFtool
- 0.823
- RVIS EVS
- 0.2
- RVIS percentile EVS
- 67.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.693
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |