ZNF501

Chr 3

zinc finger protein 501

Also known as: ZNF, ZNF52

NCBI Gene: 115560ENSG00000186446UniProt: Q96CX3

The ZNF501 protein is a transcription factor that binds DNA and is essential for maintaining Golgi structural integrity. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, affecting brain development and seizure control. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.79), suggesting some tolerance to heterozygous loss.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.79
Clinical Summary— ZNF501
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 50 VUS of 57 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.281
Z-score 1.95
OE 0.25 (0.10–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.53Z-score
OE missense 1.12 (0.99–1.28)
161 obs / 143.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.25 (0.10–0.79)
0≤0.351.4
Missense OE1.12 (0.99–1.28)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 2 / 7.9Missense obs/exp: 161 / 143.2Syn Z: -0.70
DN
0.92top 5%
GOF
0.84top 5%
LOF
0.2191th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

57 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS50
5
Pathogenic
1
Likely Pathogenic
50
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
48
2
0
50
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0488056

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF501 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Bighorn sheep T2T genome assembly reveals differences in immune genes: a potential cause of high morbidity due to respiratory pathogens
Olagunju TA et al.·bioRxiv
2025
Identification and Validation of Hub Genes and Construction of miRNA-Gene and Transcription Factor-Gene Networks in Adipogenesis of Mesenchymal Stem Cells.
Dai M et al.·Stem Cells Int
2024
Mechanism of cancer-associated fibroblast-driven thyroid cancer dedifferentiation via the ZFP57-PKM2 axis-mediated lactate secretion and therapeutic intervention with resveratrol
Ji X et al.·J Exp Clin Cancer Res
2026Functional
A tool for CRISPR-Cas9 sgRNA evaluation based on computational models of gene expression
Cohen S et al.·Genome Med
2024Functional
Genetically Regulated Gene Expression in the Brain Associated With Chronic Pain: Relationships With Clinical Traits and Potential for Drug Repurposing
Johnston KJ et al.·Biol Psychiatry
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

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