ZNF74

Chr 22

zinc finger protein 74

Also known as: COS52, ZFP520, ZNF520, hZNF7

The ZNF74 protein functions as a DNA-binding transcription factor that regulates RNA polymerase II-mediated transcription and may be involved in RNA metabolism. This gene is highly constrained against loss-of-function variants (pLI ~1.0), suggesting that mutations would likely cause severe developmental effects, though no specific disease associations have been established in the clinical literature to date.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.89
Clinical SummaryZNF74
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 1.96
OE 0.56 (0.360.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.14Z-score
OE missense 0.85 (0.780.92)
371 obs / 438.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.56 (0.360.89)
00.351.4
Missense OE0.85 (0.780.92)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 13 / 23.2Missense obs/exp: 371 / 438.4Syn Z: 1.07
DN
0.90top 5%
GOF
0.84top 5%
LOF
0.1895th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZNF74 · 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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