ZNF7

Chr 8

zinc finger protein 7

Also known as: HF.16, KOX4, zf30

NCBI Gene: 7553 ENSG00000147789 UniProt: P17097 OMIM: 194531

ZNF7 encodes a zinc finger transcription factor that regulates gene expression by binding to specific DNA sequences and modulating RNA polymerase II transcription. The gene is not loss-of-function intolerant (pLI near 0, LOEUF 0.867), suggesting it may tolerate some degree of functional variation. Currently, no definitive disease associations have been established for ZNF7 mutations in clinical practice.

OMIM 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 membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.87

Clinical Summary— ZNF7

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

98 VUS of 111 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?

0.87LOEUF

pLI 0.000

Z-score 2.09

OE 0.56 (0.38–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.23Z-score

OE missense 0.97 (0.89–1.05)

364 obs / 376.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.38–0.87)

0≤0.351.4

Missense OE?0.97 (0.89–1.05)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 15 / 26.7Missense obs/exp: 364 / 376.4Syn Z: -1.38

This gene — mechanism propensity

0.91top 5%

GOF

0.83top 10%

LOF

0.1994th %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

111 submitted variants in ClinVar

ClinVar

Classification Summary

VUS98

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	98	98
Likely Benign	3	3
Benign	0	0
Total	101	101

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

View in ClinVar →

54 pathogenic / likely-pathogenic (of 64) ClinVar copy-number / structural variants overlap ZNF7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →