THRAP3

Chr 1

thyroid hormone receptor associated protein 3

Also known as: BCLAF2, TRAP150

NCBI Gene: 9967 ENSG00000054118 UniProt: Q9Y2W1 OMIM: 603809

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables nuclear thyroid hormone receptor binding activity; phosphoprotein binding activity; and transcription coactivator activity. Involved in positive regulation of circadian rhythm and regulation of gene expression. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in exon-exon junction complex and nuclear speck. Part of mediator complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— THRAP3

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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.

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ClinVar Variants

113 VUS of 139 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 5.89

OE 0.08 (0.04–0.19)

Highly constrained

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

Missense Constraint?

2.16Z-score

OE missense 0.74 (0.69–0.81)

416 obs / 560.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.19)

0≤0.351.4

Missense OE?0.74 (0.69–0.81)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 4 / 48.1Missense obs/exp: 416 / 560.0Syn Z: -0.10

This gene — mechanism propensity

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

139 submitted variants in ClinVar

ClinVar

Classification Summary

VUS113

Likely Benign5

113

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	113	0	0	113
Likely Benign	2	1	2	5
Benign	0	0	0	0
Total	115	1	2	118

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap THRAP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →