ZNF541 encodes a transcription regulator that is essential for male fertility by controlling gene expression during meiosis in spermatocytes, specifically regulating progression through the pachytene stage and suppressing aberrant DNA double-strand break formation. This gene is extremely intolerant to loss-of-function mutations (pLI ~1.0, LOEUF 0.155), but no human diseases have been definitively associated with ZNF541 mutations to date. Given its critical role in male meiosis and high constraint scores, mutations would likely cause male infertility with autosomal dominant or recessive inheritance patterns.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.15
Clinical SummaryZNF541
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 6.17
OE 0.06 (0.030.15)
Highly constrained

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

Missense Constraint
2.64Z-score
OE missense 0.73 (0.680.78)
534 obs / 735.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.030.15)
00.351.4
Missense OE0.73 (0.680.78)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 3 / 50.1Missense obs/exp: 534 / 735.8Syn Z: 1.50
DN
0.2199th %ile
GOF
0.1999th %ile
LOF
0.86top 5%

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

LOFprediction above median · LOEUF 0.15

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZNF541 · 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.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found