ZNF541

Chr 19

zinc finger protein 541

NCBI Gene: 84215 ENSG00000118156 UniProt: Q9H0D2 OMIM: 619942

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable transcription corepressor activity. Predicted to be involved in male meiotic nuclear division and regulation of DNA-templated transcription. Predicted to be located in nucleus. Predicted to be part of histone deacetylase complex and transcription regulator complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.15

Clinical Summary— ZNF541

⚡

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

1 VUS of 10 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?

0.15LOEUF

pLI 1.000

Z-score 6.17

OE 0.06 (0.03–0.15)

Highly constrained

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

Missense Constraint?

2.64Z-score

OE missense 0.73 (0.68–0.78)

534 obs / 735.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.03–0.15)

0≤0.351.4

Missense OE?0.73 (0.68–0.78)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 3 / 50.1Missense obs/exp: 534 / 735.8Syn Z: 1.50

This gene — mechanism propensity

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

10 submitted variants in ClinVar

ClinVar

Classification Summary

VUS1

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Synonymous	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	1	1
Likely Benign	2	2
Benign	0	0
Total	3	3

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ZNF541 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →