NCOA3

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

Basic information

Region (hg38): 20:47501887-47656877

Links

ENSG00000124151 ∙ NCBI:8202 ∙ OMIM:601937 ∙ HGNC:7670 ∙ Uniprot:Q9Y6Q9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NCOA3 gene.

• Bilateral sensorineural hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCOA3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5		5
missense	1		55	3	1	60
nonsense			1			1
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	56	8	2

Highest pathogenic variant AF is 0.000414

Variants in NCOA3

This is a list of pathogenic ClinVar variants found in the NCOA3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-47622279-T-C		not specified	Uncertain significance (Oct 18, 2021)
20-47622299-C-T		not specified	Uncertain significance (Mar 31, 2024)
20-47623933-C-T		not specified	Likely benign (Dec 21, 2022)
20-47625396-A-T		not specified	Uncertain significance (Feb 28, 2024)
20-47625452-A-G		not specified	Uncertain significance (Nov 21, 2023)
20-47627063-A-G		not specified	Uncertain significance (Apr 07, 2023)
20-47627101-G-C		not specified	Uncertain significance (Jun 09, 2022)
20-47627120-A-G		not specified	Likely benign (Apr 28, 2022)
20-47627588-C-A		not specified	Uncertain significance (Feb 15, 2023)
20-47627687-G-T		not specified	Uncertain significance (Dec 19, 2022)
20-47627951-C-T		not specified	Uncertain significance (May 18, 2023)
20-47627989-C-A		not specified	Uncertain significance (Jan 23, 2024)
20-47633508-A-G		not specified	Uncertain significance (Jun 02, 2023)
20-47633621-C-T		not specified	Uncertain significance (Mar 01, 2024)
20-47633633-G-C		not specified	Uncertain significance (May 13, 2024)
20-47634056-A-G		not specified	Uncertain significance (Apr 13, 2022)
20-47634084-G-A		not specified	Uncertain significance (Mar 01, 2024)
20-47634138-T-G		not specified	Uncertain significance (Dec 07, 2023)
20-47634139-C-G		not specified	Uncertain significance (May 28, 2024)
20-47635375-C-T		not specified	Uncertain significance (Oct 25, 2022)
20-47635414-G-C		not specified	Uncertain significance (Jun 10, 2024)
20-47635455-G-A		not specified	Likely benign (Mar 16, 2024)
20-47635553-G-A		not specified	Uncertain significance (Aug 16, 2021)
20-47635599-A-G		not specified	Uncertain significance (Mar 21, 2022)
20-47635612-A-G		not specified	Uncertain significance (Sep 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCOA3	protein_coding	protein_coding	ENST00000371998	21	155021

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.541	0.459	125462	2	284	125748	0.00114

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	672	776	0.866	0.0000390	9463
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00810	0.00701
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000334	0.000326
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000924	0.000871
Middle Eastern	0.000334	0.000326
South Asian	0.00183	0.00170
Other	0.000670	0.000652

dbNSFP

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.
• Pathway: 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;Androgen receptor signaling pathway;Integrated Breast Cancer Pathway;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;Liver steatosis AOP;EGF-EGFR Signaling Pathway;Developmental Biology;Signal Transduction;transcription regulation by methyltransferase of carm1;nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells;MAPK6/MAPK4 signaling;Transcriptional regulation of white adipocyte differentiation;AndrogenReceptor;EGFR1;MAPK family signaling cascades;FOXA1 transcription factor network;Signaling by Nuclear Receptors;IL4;Estrogen-dependent gene expression;ESR-mediated signaling;Validated nuclear estrogen receptor alpha network;Retinoic acid receptors-mediated signaling;Validated nuclear estrogen receptor beta network (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.608
• rvis_EVS: -1.23
• rvis_percentile_EVS: 5.54

Haploinsufficiency Scores

• pHI: 0.749
• hipred: Y
• hipred_score: 0.704
• ghis: 0.605

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ncoa3
• Phenotype: craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; neoplasm; growth/size/body region phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; reproductive system phenotype; vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; embryo phenotype

Gene ontology

• Biological process: positive regulation of gene expression;histone acetylation;androgen receptor signaling pathway;cellular response to hormone stimulus;receptor transactivation;cell dedifferentiation;positive regulation of keratinocyte differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cellular response to estradiol stimulus;positive regulation of stem cell population maintenance;regulation of stem cell division;regulation of RNA biosynthetic process
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm;cytosol;protein-containing complex;extracellular exosome
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II complex binding;transcription coactivator activity;histone acetyltransferase activity;protein binding;nuclear receptor binding;nuclear receptor transcription coactivator activity;nuclear hormone receptor binding;thyroid hormone receptor binding;protein heterodimerization activity;protein N-terminus binding;androgen receptor binding;disordered domain specific binding