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Intellectual disability v10.97 ZBTB7B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: The 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 amber with the current evidence.; to: 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.
Intellectual disability v10.97 ZBTB7B Achchuthan Shanmugasundram Classified gene: ZBTB7B as Red List (low evidence)
Intellectual disability v10.97 ZBTB7B Achchuthan Shanmugasundram Added comment: Comment on list classification: The 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 amber with the current evidence.
Intellectual disability v10.97 ZBTB7B Achchuthan Shanmugasundram Gene: zbtb7b has been classified as Red List (Low Evidence).
Intellectual disability v10.96 ZBTB7B Achchuthan Shanmugasundram 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
Added comment: 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