MARF1

Chr 16

meiosis regulator and mRNA stability factor 1

Also known as: KIAA0430, LKAP, LMKB, PPP1R34

MARF1 encodes an essential regulator of oogenesis that represses transposable elements and protects against DNA double-strand breaks during female meiotic progression. Mutations cause primary ovarian insufficiency with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants, indicating mutations are likely to have significant clinical consequences.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.12
Clinical SummaryMARF1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 157 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 7.64
OE 0.05 (0.030.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.73Z-score
OE missense 0.75 (0.710.80)
733 obs / 972.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.030.12)
00.351.4
Missense OE0.75 (0.710.80)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 4 / 75.7Missense obs/exp: 733 / 972.5Syn Z: -1.59
DN
0.3495th %ile
GOF
0.4578th %ile
LOF
0.72top 10%

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

LOFprediction above median · LOEUF 0.12

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

200 submitted variants in ClinVar

Classification Summary

Pathogenic8
VUS157
Likely Benign6
8
Pathogenic
157
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
147
10
0
157
Likely Benign
0
4
0
2
6
Benign
0
0
0
0
0
Total0151182171

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

View in ClinVar →

Protein Context — Lollipop Plot

MARF1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗