MARF1

Chr 16

meiosis regulator and mRNA stability factor 1

Also known as: KIAA0430, LKAP, LMKB, PPP1R34

NCBI Gene: 9665 ENSG00000166783 UniProt: Q9Y4F3 OMIM: 614593

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a putative peroxisomal protein that appears to be conserved across Euteleostomi. In humans, it may be autoantigenic. [provided by RefSeq, Jul 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.12

Clinical Summary— MARF1

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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.

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ClinVar Variants

52 VUS of 81 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 7.64

OE 0.05 (0.03–0.12)

Highly constrained

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

Missense Constraint?

2.73Z-score

OE missense 0.75 (0.71–0.80)

733 obs / 972.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.05 (0.03–0.12)

0≤0.351.4

Missense OE?0.75 (0.71–0.80)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 4 / 75.7Missense obs/exp: 733 / 972.5Syn Z: -1.59

This gene — mechanism propensity

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

81 submitted variants in ClinVar

ClinVar

Classification Summary

VUS52

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	52	52
Likely Benign	0	0
Benign	0	0
Total	52	52

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap MARF1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →