ZNF500

Chr 16

zinc finger protein 500

Also known as: ZKSCAN18, ZSCAN50

NCBI Gene: 26048 ENSG00000103199 UniProt: O60304

This nuclear transcription factor regulates gene expression by binding to specific DNA sequences and modulating RNA polymerase II-mediated transcription. The gene shows very low constraint against loss-of-function variants (pLI ~0, LOEUF 0.949), and no clear disease associations have been established in the provided data. Clinical significance of variants in this gene remains uncertain.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— ZNF500

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ClinVar Variants

131 VUS of 150 total submissions

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Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.7132th %ile

GOF

0.73top 25%

LOF

0.2969th %ile

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

GOFprediction above median

DNprediction 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

150 submitted variants in ClinVar

ClinVar

Classification Summary

VUS131

Likely Benign7

131

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	131	131
Likely Benign	7	7
Benign	0	0
Total	138	138

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap ZNF500 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →