Intellectual disability
Gene: ZBTB7B

ZBTB7B (zinc finger and BTB domain containing 7B)
EnsemblGeneIds (GRCh38): ENSG00000160685
EnsemblGeneIds (GRCh37): ENSG00000160685
OMIM: 607646, Gene2Phenotype
ZBTB7B is in 3 panels

1 review

Achchuthan Shanmugasundram (Genomics England Curator)

Red List (low evidence)

Comment on list classification: Global developmental delay is reported only as a clinical feature of the broader syndrome, without formal cognitive/IQ assessment in the single reported case. No functional or mechanistic evidence specifically supports a causal role for ZBTB7B in intellectual disability. Hence, this gene should be rated red with the current evidence.
Created: 7 Aug 2026, 5:09 p.m. | Last Modified: 7 Aug 2026, 5:14 p.m.

Panel Version: 10.97

PMID:40392549 (2025) reported a 5-year-old male patient with a novel combined immunodeficiency/allergic/fibrotic syndrome, identified with a de novo heterozygous missense variant (c.1080A>C/p.Lys360Asn) by trio whole-genome sequencing. The patient presented with global developmental delay and growth failure, alongside CD4+ T-cell lymphopenia, CD8+ lymphocytosis, severe early-onset allergic disease, fibroinflammatory interstitial lung disease, corneal defects, and sensorineural hearing loss.

Extensive functional studies supported a multimorphic mechanism combining dominant-negative, loss-of-function, and neomorphic gain-of-function effects on DNA binding and downstream gene targets; however, all functional validation (lentiviral gene-transfer in healthy-donor T cells and pulmonary fibroblasts, luciferase, EMSA, HT-SELEX, ChIP-seq) was directed at immune and fibrotic mechanisms, with no neuronal/CNS cell model or evidence directly linking K360N to a neurodevelopmental mechanism.

This gene has not yet been associated with relevant phenotypes either in OMIM or in ClinGen (last accessed 07 August 2026).
Sources: Literature
Created: 7 Aug 2026, 5:01 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
inborn error of immunity, MONDO:0003778; interstitial lung disease, MONDO:0015925; Global developmental delay, HP:0001263

Publications

40392549

Created: 7 Aug 2026, 5:01 p.m.
Last Modified: 7 Aug 2026, 5:14 p.m.
Panel version: 10.96

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Red
Literature

Phenotypes

inborn error of immunity, MONDO:0003778
interstitial lung disease, MONDO:0015925
Global developmental delay, HP:0001263

OMIM

607646

Clinvar variants

Variants in ZBTB7B

Penetrance

None

Publications

40392549

Panels with this gene

History Filter Activity

7 Aug 2026, Gel status: 1

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: zbtb7b has been classified as Red List (Low Evidence).

7 Aug 2026, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

gene: ZBTB7B was added gene: ZBTB7B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ZBTB7B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZBTB7B were set to 40392549 Phenotypes for gene: ZBTB7B were set to inborn error of immunity, MONDO:0003778; interstitial lung disease, MONDO:0015925; Global developmental delay, HP:0001263 Review for gene: ZBTB7B was set to RED

Intellectual disability Gene: ZBTB7B