ZNF33B

Chr 10

zinc finger protein 33B

Also known as: KOX2, KOX31, ZNF11B

NCBI Gene: 7582ENSG00000196693UniProt: Q06732

The protein is a zinc finger transcription factor that regulates gene expression. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
0.78
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ZNF33B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 128 VUS of 150 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
0.78LOEUF
pLI 0.000
Z-score 2.46
OE 0.50 (0.33–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.22Z-score
OE missense 1.03 (0.95–1.12)
401 obs / 388.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.50 (0.33–0.78)
0≤0.351.4
Missense OE1.03 (0.95–1.12)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 14 / 28.0Missense obs/exp: 401 / 388.7Syn Z: -1.18
DN
0.93top 5%
GOF
0.88top 5%
LOF
0.1498th %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

150 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS128
Likely Benign5
Benign2
Conflicting1
9
Pathogenic
1
Likely Pathogenic
128
VUS
5
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
0
124
4
0
128
Likely Benign
0
4
1
0
5
Benign
0
1
1
0
2
Conflicting
—1
Total0129160146

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF33B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients