NCOA1
protein-codingnuclear receptor coactivator 1, the group of PAS domain containing|Basic helix-loop-helix proteins|Lysine acetyltransferases
Gene summary
The protein encoded by this gene acts as a transcriptional coactivator for steroid and nuclear hormone receptors. It is a member of the p160/steroid receptor coactivator (SRC) family and like other family members has histone acetyltransferase activity and contains a nuclear localization signal, as well as bHLH and PAS domains. The product of this gene binds nuclear receptors directly and stimulates the transcriptional activities in a hormone-dependent fashion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~279.4 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 NCOA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003743.5. 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 | 4 | 160 | 3 | 167 | ||
| missense | 401 | 8 | 409 | |||
| nonsense | 8 | 8 | ||||
| start loss | 0 | |||||
| frameshift | 5 | 5 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 429 | 168 | 3 | 600 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003734.3 | 19 | MANE Select | |
| Ensembl | ENSP00000320940.5 | 19 | MANE Select | |
| RefSeq | NP_001349879.1 | 19 | Standard | |
| RefSeq | NP_001349881.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Breast cancer - Homo sapiens (human)
- Thyroid hormone signaling pathway - Homo sapiens (human)
- Estrogen signaling pathway - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Androgen receptor signaling pathway
Biological Process
- positive regulation of transcription from RNA polymerase II promoter by galactose
- regulation of thyroid hormone mediated signaling pathway
- transcription, DNA-templated
- bile acid and bile salt transport
- regulation of lipid metabolic process
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- chromatin binding
- transcription coactivator activity
- histone acetyltransferase activity
Cellular Component
- nuclear chromatin
- nucleus
- nucleoplasm
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000406961
- Coding exons
- 19
- Length
- 278789
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125747
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.35 | 599 | 784 | 0.764 | 0.0000404 | 9451 |
| Missense (PolyPhen) | 145 | 262.38 | 0.55264 | 3171 | ||
| Synonymous | 0.567 | 279 | 291 | 0.958 | 0.0000159 | 2843 |
| Loss of Function | 6.56 | 10 | 68.6 | 0.146 | 0.00000371 | 763 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3. {ECO:0000269|PubMed:10449719, ECO:0000269|PubMed:12954634, ECO:0000269|PubMed:7481822, ECO:0000269|PubMed:9223281, ECO:0000269|PubMed:9223431, ECO:0000269|PubMed:9296499, ECO:0000269|PubMed:9427757}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children. {ECO:0000269|PubMed:15313887}.;
Recessive Scores
- pRec
- 0.385
Intolerance Scores
- LoFtool
- 0.182
- RVIS EVS
- -2.19
- RVIS percentile EVS
- 1.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |