NCOA1

nuclear receptor coactivator 1, the group of PAS domain containing|Basic helix-loop-helix proteins|Lysine acetyltransferases

Basic information

Region (hg38): 2:24491253-24770702

Links

ENSG00000084676 ∙ NCBI:8648 ∙ OMIM:602691 ∙ HGNC:7668 ∙ Uniprot:Q15788 ∙ 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 NCOA1 gene.

• Inborn genetic diseases (48 variants)
• NCOA1-related condition (36 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCOA1 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			1	5	1	7
missense			75	2		77
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	76	7	1

Variants in NCOA1

This is a list of pathogenic ClinVar variants found in the NCOA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-24658694-A-G		NCOA1-related disorder	Uncertain significance (Sep 22, 2022)
2-24658704-C-A		NCOA1-related disorder	Likely benign (Jul 28, 2022)
2-24658704-C-T		NCOA1-related disorder	Likely benign (May 20, 2021)
2-24658753-A-C		NCOA1-related disorder	Uncertain significance (Aug 24, 2023)
2-24658770-G-A		NCOA1-related disorder	Likely benign (Jan 10, 2022)
2-24665752-G-A		NCOA1-related disorder	Likely benign (Dec 03, 2020)
2-24665821-T-G		not specified	Uncertain significance (Oct 24, 2023)
2-24665823-G-C		NCOA1-related disorder	Uncertain significance (Jan 22, 2024)
2-24665882-G-A		not specified	Uncertain significance (Sep 14, 2023)
2-24665896-A-C			Benign (Jun 15, 2018)
2-24673385-C-T		NCOA1-related disorder	Likely benign (Feb 14, 2024)
2-24673389-G-A		not specified	Uncertain significance (Dec 14, 2023)
2-24673415-T-C		NCOA1-related disorder	Likely benign (Oct 29, 2019)
2-24683010-G-A		NCOA1-related disorder	Likely benign (Dec 05, 2019)
2-24683059-A-T		not specified	Uncertain significance (Jan 30, 2024)
2-24683061-C-T		NCOA1-related disorder	Likely benign (Aug 27, 2019)
2-24683080-G-A		not specified	Uncertain significance (Jun 01, 2023)
2-24683113-C-T		NCOA1-related disorder	Likely benign (Aug 24, 2022)
2-24691587-A-G		NCOA1-related disorder	Likely benign (Oct 29, 2019)
2-24691623-T-G			Likely benign (Jul 01, 2022)
2-24693310-G-C			Likely benign (Jul 01, 2022)
2-24697701-C-A			Likely benign (Jul 01, 2022)
2-24697716-A-G		NCOA1-related disorder	Likely benign (Jan 05, 2024)
2-24697725-G-A		NCOA1-related disorder	Uncertain significance (Nov 07, 2023)
2-24697774-T-A		not specified	Uncertain significance (Dec 15, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCOA1	protein_coding	protein_coding	ENST00000406961	19	278789

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000187	125725	0	22	125747	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	599	784	0.764	0.0000404	9451
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000215	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000970	0.0000967
Middle Eastern	0.000163	0.000163
South Asian	0.000132	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• 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);Androgen receptor signaling pathway;Energy Metabolism;Leptin signaling pathway;Adipogenesis;JAK-STAT;Aryl Hydrocarbon Receptor Pathway;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;IL-6 signaling pathway;Liver steatosis AOP;Developmental Biology;Signal Transduction;mechanism of gene regulation by peroxisome proliferators via ppara;Phase I - Functionalization of compounds;nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Metabolism of lipids;Endogenous sterols;Chromatin modifying enzymes;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Transcriptional regulation of white adipocyte differentiation;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Recycling of bile acids and salts;Bile acid and bile salt metabolism;Metabolism of steroids;AndrogenReceptor;HATs acetylate histones;TGF_beta_Receptor;Glucocorticoid receptor regulatory network;Signaling by Nuclear Receptors;Chromatin organization;RXR and RAR heterodimerization with other nuclear receptor;Leptin;Estrogen-dependent gene expression;IL6;ESR-mediated signaling;Notch-mediated HES/HEY network;Validated nuclear estrogen receptor alpha network;Retinoic acid receptors-mediated signaling;HIF-1-alpha transcription factor network;Regulation of Androgen receptor activity;Validated nuclear estrogen receptor beta network;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.385

Intolerance Scores

• loftool: 0.182
• rvis_EVS: -2.19
• rvis_percentile_EVS: 1.39

Haploinsufficiency Scores

• pHI: 0.977
• hipred: Y
• hipred_score: 0.765
• ghis: 0.642

Essentials

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

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ncoa1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; growth/size/body region phenotype; reproductive system phenotype; 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; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• 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;androgen receptor signaling pathway;cellular response to hormone stimulus;positive regulation of apoptotic process;histone H4 acetylation;positive regulation of neuron differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;labyrinthine layer morphogenesis;cellular response to Thyroglobulin triiodothyronine;regulation of cellular response to drug
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytosol;plasma membrane;protein-containing complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;transcription coactivator activity;histone acetyltransferase activity;protein binding;nuclear receptor binding;aryl hydrocarbon receptor binding;enzyme binding;estrogen receptor binding;nuclear receptor transcription coactivator activity;nuclear hormone receptor binding;protein dimerization activity;protein N-terminus binding;androgen receptor binding