NCOA3

protein-coding

nuclear receptor coactivator 3, the group of Basic helix-loop-helix proteins|Lysine acetyltransferases|PAS domain containing

Gene summary

The protein encoded by this gene is a nuclear receptor coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator functions. The encoded protein has histone acetyltransferase activity and recruits p300/CBP-associated factor and CREB binding protein as part of a multisubunit coactivation complex. This protein is initially found in the cytoplasm but is translocated into the nucleus upon phosphorylation. Several transcript variants encoding different isoforms have been found for this gene. In addition, a polymorphic repeat region is found in the C-terminus of the encoded protein. [provided by RefSeq, Mar 2010]

MANE transcript

NM_181659.3

Inheritance

ClinVar variants

P:1U:175B:15

Top phenotype

Bilateral sensorineural hearing impairment

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr20:47,501,887-47,656,877

External References & Databases

Ensembl (ENSG00000124151)

Transcript & Mutation Effects

hg38 • Region Span ~155.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant nonsyndromic hearing lossLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NCOA3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 171

not providedTotal: 7

Bilateral sensorineural hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181659.3. 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 clinvar	4 clinvar		8
missense	1 clinvar		166 clinvar	10 clinvar	1 clinvar	178
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	175	14	1	191

Highest pathogenic variant AF is 0.00023542444

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181659.3	RefSeq	NP_858045.1	21	MANE Select
ENST00000371998.8	Ensembl	ENSP00000361066.3	21	MANE Select
NM_001174087.2	RefSeq	NP_001167558.1	21	Standard
NM_001174088.2	RefSeq	NP_001167559.1	21	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)
Glucocorticoid Pathway (Peripheral Tissue), Pharmacodynamics

Biological Process

positive regulation of gene expression
histone acetylation
androgen receptor signaling pathway
cellular response to hormone stimulus
receptor transactivation

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
RNA polymerase II complex binding
transcription coactivator activity
histone acetyltransferase activity
protein binding

Cellular Component

nuclear chromatin
nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371998
Coding exons: 21
Length: 155021
Individuals with no LoFs: 125462
Homozygous LoFs: 2
Heterozygous LoFs: 284
Defined: 125748
p: 0.00114

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.33	672	776	0.866	0.0000390	9463
Missense (PolyPhen)		187	251.23	0.74432		3006
Synonymous	0.111	265	267	0.991	0.0000133	2685
Loss of Function	6.15	16	72.5	0.221	0.00000411	754

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0077	0.0066	notable
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00092	0.00087	rare
South Asian	0.0018	0.0017	notable
Other	0.00067	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via its interaction with the NFKB1 subunit.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.608
RVIS EVS: -1.23
RVIS percentile EVS: 5.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium