ZBTB18

Chr 1AD

zinc finger and BTB domain containing 18

Also known as: C1DELq42q44, C1DELq43q44, C2H2-171, DEL1Q42Q44, DEL1Q43Q44, MRD22, RP58, TAZ-1

NCBI Gene: 10472ENSG00000179456UniProt: Q99592OMIM: 608433

The protein is a C2H2-type zinc finger transcriptional repressor that recognizes specific DNA sequence motifs and recruits chromatin components to repress genes involved in neuronal development. Mutations cause intellectual developmental disorder, autosomal dominant 22 through a loss-of-function mechanism. The condition follows autosomal dominant inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.181 OMIM phenotype
Clinical Summary— ZBTB18
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
166 unique Pathogenic / Likely Pathogenic· 169 VUS of 476 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.18LOEUF
pLI 0.997
Z-score 3.79
OE 0.00 (0.00–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.43Z-score
OE missense 0.46 (0.41–0.53)
150 obs / 323.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.18)
0≤0.351.4
Missense OE0.46 (0.41–0.53)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 0 / 16.7Missense obs/exp: 150 / 323.7Syn Z: -0.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveZBTB18-related intellectual developmental disorderLOFAD
DN
0.2898th %ile
GOF
0.3094th %ile
LOF
0.82top 5%

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

LOFprediction above median · 1 literature citation · 28% of P/LP variants are LoF · LOEUF 0.18

Literature Evidence

LOFHere we provide additional evidence for haploinsufficiency or dysfunction of the ZBTB18 gene as the cause of ID in five unrelated patients with variable syndromic features who underwent whole exome sequencing revealing separate de novo pathogenic or likely pathogenic variants in ZBTB18 (two missensePMID:27598823

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

476 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic122
Likely Pathogenic44
VUS169
Likely Benign102
Benign16
Conflicting14
122
Pathogenic
44
Likely Pathogenic
169
VUS
102
Likely Benign
16
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
32
4
86
0
122
Likely Pathogenic
14
24
6
0
44
VUS
3
152
13
1
169
Likely Benign
0
13
2
87
102
Benign
0
13
0
3
16
Conflicting
—14
Total4920610791467

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

View in ClinVar →

Protein Context — Lollipop Plot

ZBTB18 · 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