TRIB1

Chr 8

tribbles pseudokinase 1

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

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.

Summary from RefSeq, UniProt
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0
Active trials
20
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.46
LOEUF
LOF
Mechanism· predicted
Clinical SummaryTRIB1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
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GeneReview available — TRIB1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.833
Z-score 2.68
OE 0.10 (0.030.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.21Z-score
OE missense 0.73 (0.630.85)
119 obs / 162.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.030.46)
00.351.4
Missense OE0.73 (0.630.85)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 1 / 10.3Missense obs/exp: 119 / 162.4Syn Z: -1.05
DN
0.3991th %ile
GOF
0.4677th %ile
LOF
0.68top 10%

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

LOFprediction above median · LOEUF 0.46

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TRIB1 · 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

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗