ZNF34

Chr 8

zinc finger protein 34

Also known as: KOX32

NCBI Gene: 80778 ENSG00000196378 UniProt: Q8IZ26 OMIM: 194526

The protein functions as a DNA-binding transcription factor that regulates gene expression by RNA polymerase II. Currently, no confirmed human diseases have been definitively associated with ZNF34 mutations in the literature. The gene shows low constraint to loss-of-function variation (pLI = 0.0007), suggesting it may be tolerant to such mutations.

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. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.72

Clinical Summary— ZNF34

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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

62 VUS of 71 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?

0.72LOEUF

pLI 0.001

Z-score 2.54

OE 0.41 (0.25–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.21Z-score

OE missense 0.81 (0.73–0.90)

257 obs / 317.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.25–0.72)

0≤0.351.4

Missense OE?0.81 (0.73–0.90)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 9 / 21.8Missense obs/exp: 257 / 317.8Syn Z: 0.81

This gene — mechanism propensity

0.79top 25%

GOF

0.74top 25%

LOF

0.3163th %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

71 submitted variants in ClinVar

ClinVar

Classification Summary

VUS62

Likely Benign4

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	62	62
Likely Benign	4	4
Benign	0	0
Total	66	66

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

View in ClinVar →

55 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap ZNF34 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →