ZNF16

Chr 8

zinc finger protein 16

Also known as: HZF1, KOX9

NCBI Gene: 7564 ENSG00000170631 UniProt: P17020 OMIM: 601262

This gene encodes a zinc finger transcriptional activator that promotes cell proliferation and facilitates erythroid and megakaryocytic cell differentiation while inhibiting apoptosis. The gene shows no constraint against loss-of-function variants (very low pLI score), suggesting that ZNF16 mutations may not cause severe developmental disorders. No well-established Mendelian diseases have been definitively linked to ZNF16 mutations in current clinical databases.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains multiple tandem zinc finger motifs. The encoded protein is involved in the differentiation of erythroid and megakaryocytic cells. This gene is located in a cluster of related genes on chromosome 8 encoding zinc finger proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.25

Clinical Summary— ZNF16

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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

95 VUS of 109 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?

1.25LOEUF

pLI 0.000

Z-score 0.61

OE 0.86 (0.61–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.12Z-score

OE missense 0.98 (0.90–1.07)

373 obs / 379.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.61–1.25)

0≤0.351.4

Missense OE?0.98 (0.90–1.07)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 20 / 23.2Missense obs/exp: 373 / 379.7Syn Z: -0.38

This gene — mechanism propensity

0.89top 5%

GOF

0.80top 10%

LOF

0.3066th %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

109 submitted variants in ClinVar

ClinVar

Classification Summary

VUS95

Likely Benign10

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	95	0	95
Likely Benign	8	2	10
Benign	0	0	0
Total	103	2	105

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

View in ClinVar →

54 pathogenic / likely-pathogenic (of 66) ClinVar copy-number / structural variants overlap ZNF16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →