TRIB1

Chr 8

tribbles pseudokinase 1

Also known as: C8FW, GIG-2, GIG2, SKIP1, TRB-1, TRB1

NCBI Gene: 10221 ENSG00000173334 UniProt: Q96RU8

The TRIB1 protein functions as an adapter that regulates protein degradation by directing COP1 ubiquitin ligase activity toward specific substrates like CEBPA, and controls myeloid cell differentiation including macrophages, eosinophils, and neutrophils. Mutations in TRIB1 cause autosomal dominant intellectual disability with macrocephaly, seizures, and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not well-tolerated.

GeneReviews ResearchSummary from RefSeq, UniProt

Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; mitogen-activated protein kinase kinase binding activity; and protein kinase inhibitor activity. Involved in several processes, including JNK cascade; negative regulation of lipopolysaccharide-mediated signaling pathway; and regulation of protein kinase activity. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2025]

GeneReviews ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.46

LOEUF

LOF

Mechanism· predicted

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GeneReview available — TRIB1