MAF1
Chr 8MAF1 negative regulator of RNA polymerase III
MAF1 encodes a protein that represses RNA polymerase III-mediated transcription of tRNAs, 5S rRNA, and other small non-coding RNAs in response to nutritional and cellular stress conditions. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and multiple congenital anomalies. The gene is highly constrained against loss-of-function variants (pLI 0.95, LOEUF 0.35), indicating that complete loss of function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
114 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 56 | 0 | 56 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 22 | 11 | 0 | 33 |
Likely Benign | 0 | 3 | 0 | 1 | 4 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 25 | 72 | 2 | 99 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MAF1 · 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
External Resources
Links to major genomics databases and tools