THRAP3

Chr 1

thyroid hormone receptor associated protein 3

Also known as: BCLAF2, TRAP150

The protein functions as a transcriptional coactivator and pre-mRNA splicing regulator that remains associated with spliced mRNA and controls mRNA stability and decay. Mutations cause autosomal dominant developmental delay, intellectual disability, and epilepsy with onset in infancy or early childhood. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.19
Clinical SummaryTHRAP3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 117 VUS of 151 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 5.89
OE 0.08 (0.040.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.16Z-score
OE missense 0.74 (0.690.81)
416 obs / 560.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.040.19)
00.351.4
Missense OE0.74 (0.690.81)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 4 / 48.1Missense obs/exp: 416 / 560.0Syn Z: -0.10
DN
0.3395th %ile
GOF
0.3094th %ile
LOF
0.85top 5%

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

LOFprediction above median · LOEUF 0.19

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

151 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic2
VUS117
Likely Benign5
6
Pathogenic
2
Likely Pathogenic
117
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
2
0
2
VUS
0
113
4
0
117
Likely Benign
0
2
1
2
5
Benign
0
0
0
0
0
Total0115132130

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

THRAP3 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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