NCOA6
protein-codingnuclear receptor coactivator 6
Gene summary
The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcriptional activator functions. This protein has been shown to be involved in the hormone-dependent coactivation of several receptors, including prostanoid, retinoid, vitamin D3, thyroid hormone, and steroid receptors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~136.6 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 NCOA6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014071.5. 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 | 5 | 9 | 8 | 22 | ||
| missense | 247 | 10 | 3 | 260 | ||
| nonsense | 7 | 7 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 266 | 19 | 11 | 296 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054790.2 | 13 | MANE Select | |
| Ensembl | ENSP00000351894.2 | 13 | MANE Select | |
| RefSeq | NP_001229468.1 | 12 | Standard | |
| RefSeq | NP_001305169.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Constitutive Androstane Receptor Pathway
- Nuclear Receptors Meta-Pathway
- Liver steatosis AOP
- Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
- Metabolism of lipids
Biological Process
- DNA replication
- DNA repair
- DNA recombination
- DNA-templated transcription, initiation
- cellular response to DNA damage stimulus
Molecular Function
- chromatin binding
- transcription coactivator activity
- protein binding
- enzyme binding
- estrogen receptor binding
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- cytosol
- histone methyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374796
- Coding exons
- 13
- Length
- 128731
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125748
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.954 | 1035 | 1.13e+3 | 0.920 | 0.0000583 | 13520 |
| Missense (PolyPhen) | 332 | 419.52 | 0.79138 | 5220 | ||
| Synonymous | -1.02 | 449 | 422 | 1.06 | 0.0000236 | 4273 |
| Loss of Function | 6.80 | 13 | 77.7 | 0.167 | 0.00000413 | 793 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.000098 | 0.000098 | 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. Coactivates expression in an agonist- and AF2-dependent manner. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Probably functions as a general coactivator, rather than just a nuclear receptor coactivator. May also be involved in the coactivation of the NF-kappa-B pathway. May coactivate expression via a remodeling of chromatin and its interaction with histone acetyltransferase proteins.;
Recessive Scores
- pRec
- 0.355
Intolerance Scores
- LoFtool
- 0.354
- RVIS EVS
- -2.02
- RVIS percentile EVS
- 1.71
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.864
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |