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: Q99592

This gene encodes a C2H2-type zinc finger protein which acts a transcriptional repressor of genes involved in neuronal development. The encoded protein recognizes a specific sequence motif and recruits components of chromatin to target genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 22MIM #612337
AD
195
ClinVar variants
23
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ZBTB18
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 103 VUS of 195 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.46 (0.41–0.53)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 0 / 16.7Missense obs/exp: 150 / 323.7Syn Z: -0.31

ClinVar Variant Classifications

195 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic3
VUS103
Likely Benign55
Benign9
Conflicting5
20
Pathogenic
3
Likely Pathogenic
103
VUS
55
Likely Benign
9
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
2
11
0
20
Likely Pathogenic
0
1
2
0
3
VUS
1
94
8
0
103
Likely Benign
0
6
0
49
55
Benign
0
8
0
1
9
Conflicting
—5
Total81112150195

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.

Gene2Phenotype Curations

ZBTB18-related intellectual developmental disorder

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 22

MIM #612337

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.
Wang T et al.·Nat Commun
2020
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
ZBTB18 regulates cytokine expression and affects microglia/macrophage recruitment and commitment in glioblastoma.
Ferrarese R et al.·Commun Biol
2024
Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).
Viswanathan S et al.·Ann Neurol
2024
A de novo variant in ZBTB18 gene caused autosomal dominant non-syndromic intellectual disability 22 syndrome: A case report and literature review.
Yang F et al.·Medicine (Baltimore)
2024Review
Toward clinical and molecular understanding of pathogenic variants in the ZBTB18 gene.
van der Schoot V et al.·Mol Genet Genomic Med
2018
[Analysis of clinical features and ZBTB18 gene variant in a child with autosomal dominant mental disorder type 22].
Zhang J et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
Prenatal diagnosis of a likely pathogenic variant in ZBTB18: Natural evolution of fetal phenotype including the long bones and corpus callosum.
Birnbaum R et al.·Am J Med Genet A
2022Case report
A novel heterozygous ZBTB18 missense mutation in a family with non-syndromic intellectual disability.
Li N et al.·Neurogenetics
2023
Expanding the Clinical and Molecular Spectrum of FOXG1- and ZBTB18-Associated Neurodevelopmental Disorders.
Brea-Fernández AJ et al.·Cytogenet Genome Res
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools