MARCHF8
Chr 10membrane associated ring-CH-type finger 8
Also known as: CMIR, MARCH-VIII, MARCH8, MIR, RNF178, c-MIR
MARCHF8 encodes a membrane-bound E3 ubiquitin ligase that regulates immune responses by ubiquitinating and targeting various proteins including viral envelope proteins, MHC class II molecules, and immune receptors for degradation. Mutations cause autosomal recessive primary immunodeficiency with recurrent infections, growth retardation, and developmental delays typically presenting in early childhood. The gene shows no intolerance to loss-of-function variants based on population genetics data.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
24 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 11 |
Likely Pathogenic | — | — | — | — | 2 |
VUS | — | — | — | — | 4 |
Likely Benign | — | — | — | — | 2 |
Benign | — | — | — | — | 1 |
| Total | — | 20 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MARCHF8 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools