ZNF267

Chr 16

zinc finger protein 267

Also known as: HZF2

NCBI Gene: 10308 ENSG00000185947 UniProt: Q14586

ZNF267 encodes a zinc finger protein that binds DNA and regulates transcription by RNA polymerase II in the nucleus. The gene shows low constraint against loss-of-function variants (pLI = 0.02, LOEUF = 1.56), and no definitive disease associations have been established for mutations in this gene. Current evidence does not support ZNF267 as a cause of pediatric neurological disorders.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity and zinc ion 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]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.55

Clinical Summary— ZNF267

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

79 VUS of 89 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.55LOEUF

pLI 0.017

Z-score 0.74

OE 0.63 (0.29–1.55)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.57Z-score

OE missense 0.92 (0.84–1.00)

351 obs / 382.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.29–1.55)

0≤0.351.4

Missense OE?0.92 (0.84–1.00)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 3 / 4.7Missense obs/exp: 351 / 382.6Syn Z: 1.07

This gene — mechanism propensity

0.91top 5%

GOF

0.84top 5%

LOF

0.2386th %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

89 submitted variants in ClinVar

ClinVar

Classification Summary

VUS79

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	79	0	79
Likely Benign	2	2	4
Benign	0	0	0
Total	81	2	83

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap ZNF267 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →