MAF1

Chr 8

MAF1 negative regulator of RNA polymerase III

NCBI Gene: 84232ENSG00000179632UniProt: Q9H063OMIM: 610210

This gene encodes a protein that is similar to Maf1, a Saccharomyces cerevisiae protein highly conserved in eukaryotic cells. Yeast Maf1 is a negative effector of RNA polymerase III (Pol III). It responds to changes in the cellular environment and represses pol III transcription. Biochemical studies identified the initiation factor TFIIIB as a target for Maf1-dependent repression. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.34
Clinical Summary— MAF1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 VUS of 42 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — MAF1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.34LOEUF
pLI 0.948
Z-score 3.18
OE 0.07 (0.03–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.22Z-score
OE missense 0.48 (0.39–0.59)
69 obs / 143.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.07 (0.03–0.34)
0≤0.351.4
Missense OE?0.48 (0.39–0.59)
0≤0.61.4
Synonymous OE?1.55
0≤1.21.6
LoF obs/exp: 1 / 13.7Missense obs/exp: 69 / 143.9Syn Z: -3.25

This gene — mechanism propensity

DN
0.3991th %ile
GOF
0.3292th %ile
LOF
0.64top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.34

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

42 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22
Likely Benign4
Benign1
22
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
22
0
0
22
Likely Benign
0
3
0
1
4
Benign
0
0
0
1
1
Total0250227

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

61 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap MAF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

MAF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients