ZNF75A

Chr 16

zinc finger protein 75A

NCBI Gene: 7627 ENSG00000162086 UniProt: Q96N20 OMIM: 601473

ZNF75A encodes a transcription factor that binds to specific DNA sequences and regulates gene transcription by RNA polymerase II in the nucleus. This gene is not highly constrained against loss-of-function variants and is not currently associated with any established Mendelian diseases or clinical phenotypes in pediatric patients.

OMIM ResearchSummary from RefSeq, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.00

Clinical Summary— ZNF75A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

30 VUS of 38 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.002

Z-score 1.57

OE 0.51 (0.28–1.00)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.88–1.14)

154 obs / 154.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.28–1.00)

0≤0.351.4

Missense OE?1.00 (0.88–1.14)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 6 / 11.8Missense obs/exp: 154 / 154.2Syn Z: -0.74

This gene — mechanism propensity

0.7325th %ile

GOF

0.7029th %ile

LOF

0.3454th %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

38 submitted variants in ClinVar

ClinVar

Classification Summary

VUS30

Likely Benign3

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	30	30
Likely Benign	3	3
Benign	0	0
Total	33	33

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap ZNF75A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →