THRAP3
protein-codingthyroid hormone receptor associated protein 3, the group of WTAP complex|Spliceosomal A complex
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~80.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to THRAP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005119.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 4 | |||
| missense | 117 | 2 | 119 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 120 | 4 | 0 | 124 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005110.2 | 10 | MANE Select | |
| Ensembl | ENSP00000346634.5 | 10 | MANE Select | |
| RefSeq | NP_001308400.1 | 10 | Standard | |
| RefSeq | NP_001308402.1 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Interactome of polycomb repressive complex 2 (PRC2)
- Developmental Biology
- Transcriptional regulation of white adipocyte differentiation
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- nuclear-transcribed mRNA catabolic process
- transcription initiation from RNA polymerase II promoter
- mRNA processing
- circadian rhythm
Molecular Function
- RNA polymerase II distal enhancer sequence-specific DNA binding
- transcription coregulator activity
- transcription coactivator activity
- RNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- mediator complex
- nuclear speck
- exon-exon junction complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354618
- Coding exons
- 10
- Length
- 80942
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125746
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.16 | 416 | 560 | 0.743 | 0.0000347 | 6194 |
| Missense (PolyPhen) | 197 | 236.85 | 0.83175 | 2986 | ||
| Synonymous | -0.0994 | 194 | 192 | 1.01 | 0.00000971 | 1886 |
| Loss of Function | 5.89 | 4 | 48.1 | 0.0832 | 0.00000346 | 527 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-ARNTL/BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}.;
Recessive Scores
- pRec
- 0.255
Intolerance Scores
- RVIS EVS
- -0.62
- RVIS percentile EVS
- 17.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.952
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |