TRIP4

Chr 15AR

thyroid hormone receptor interactor 4

Also known as: ASC-1, ASC1, HsT17391, MDCDC, SMABF1, ZC2HC5

This protein functions as a transcription coactivator that associates with nuclear receptors and basal transcription factors to facilitate gene transcription, and also plays a role in ribosome quality control during protein translation. Mutations cause spinal muscular atrophy with congenital bone fractures type 1 and congenital muscular dystrophy (Davignon-Chauveau type), both presenting in early infancy with severe muscle weakness and bone fragility. These conditions follow autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.672 OMIM phenotypes
Clinical SummaryTRIP4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.67LOEUF
pLI 0.000
Z-score 3.18
OE 0.45 (0.300.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.57Z-score
OE missense 0.91 (0.821.00)
275 obs / 302.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.45 (0.300.67)
00.351.4
Missense OE0.91 (0.821.00)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 17 / 38.2Missense obs/exp: 275 / 302.9Syn Z: -0.37
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTRIP4-related prenatal spinal muscular atrophy and congenital bone fracturesLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6454th %ile
GOF
0.4776th %ile
LOF
0.3454th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TRIP4 · 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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