ZBTB46

Chr 20

zinc finger and BTB domain containing 46

Also known as: BTBD4, BZEL, RINZF, ZNF340, dJ583P15.7, dJ583P15.8

NCBI Gene: 140685ENSG00000130584UniProt: Q86UZ6

ZBTB46 encodes a transcription repressor that regulates dendritic cell differentiation and immune tolerance to gut microbiota. The gene is highly constrained against loss-of-function variants (pLI 0.81, LOEUF 0.40), but no definitive Mendelian disease associations have been established in humans to date.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
4
Pubs (1 yr)
41
P/LP submissions
0%
P/LP missense
0.40
LOEUF
LOF
Mechanism· predicted
Clinical Summary— ZBTB46
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 108 VUS of 159 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.809
Z-score 3.68
OE 0.17 (0.09–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.24Z-score
OE missense 0.69 (0.63–0.76)
287 obs / 415.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.09–0.40)
0≤0.351.4
Missense OE0.69 (0.63–0.76)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 4 / 23.0Missense obs/exp: 287 / 415.2Syn Z: -1.35
DN
0.4686th %ile
GOF
0.3194th %ile
LOF
0.73top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.40

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

159 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic8
VUS108
Likely Benign2
Conflicting1
33
Pathogenic
8
Likely Pathogenic
108
VUS
2
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
8
0
8
VUS
0
93
15
0
108
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Conflicting
—1
Total094561152

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB46 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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 5 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