NCOA4
protein-codingnuclear receptor coactivator 4
Gene summary
This gene encodes an androgen receptor coactivator. The encoded protein interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. Chromosomal translocations between this gene and the ret tyrosine kinase gene, also located on chromosome 10, have been associated with papillary thyroid carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes are present on chromosomes 4, 5, 10, and 14. [provided by RefSeq, Feb 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.5 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 NCOA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001145263.2. 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 | 1 | 1 | 1 | 3 | ||
| missense | 62 | 7 | 4 | 73 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 64 | 8 | 5 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001138735.1 | 9 | MANE Select | |
| Ensembl | ENSP00000462943.1 | 9 | MANE Select | |
| RefSeq | NP_001138732.1 | 10 | Standard | |
| RefSeq | NP_001138733.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ncoa4 | Danio rerio | Structure: nucleate erythrocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pathways in cancer - Homo sapiens (human)
- Ferroptosis - Homo sapiens (human)
- Thyroid cancer - Homo sapiens (human)
- Androgen receptor signaling pathway
- Exercise-induced Circadian Regulation
Biological Process
- protein targeting to lysosome
- cellular iron ion homeostasis
- male gonad development
- androgen receptor signaling pathway
- positive regulation of transcription, DNA-templated
Molecular Function
- transcription coactivator activity
- androgen receptor binding
Cellular Component
- nucleus
- autolysosome
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Enhances the androgen receptor transcriptional activity in prostate cancer cells. Ligand-independent coactivator of the peroxisome proliferator-activated receptor (PPAR) gamma. {ECO:0000269|PubMed:10347167}.;
Recessive Scores
- pRec
- 0.292
Intolerance Scores
- LoFtool
- 0.729
- RVIS EVS
- 1.46
- RVIS percentile EVS
- 95.21
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |