NCOA2

nuclear receptor coactivator 2, the group of Lysine acetyltransferases|PAS domain containing|Basic helix-loop-helix proteins

Basic information

Region (hg38): 8:70109781-70403808

Links

ENSG00000140396 ∙ NCBI:10499 ∙ OMIM:601993 ∙ HGNC:7669 ∙ Uniprot:Q15596 ∙ 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 NCOA2 gene.

• Inborn genetic diseases (42 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NCOA2 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				3	2	5
missense			41	2		43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	41	5	2

Variants in NCOA2

This is a list of pathogenic ClinVar variants found in the NCOA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-70121331-T-C		not specified	Uncertain significance (May 16, 2022)
8-70121387-T-C		not specified	Uncertain significance (Feb 06, 2024)
8-70123898-T-C		not specified	Uncertain significance (Aug 12, 2021)
8-70123978-C-A		not specified	Uncertain significance (Jun 24, 2022)
8-70124696-G-A			Likely benign (Jul 19, 2018)
8-70124824-T-A		not specified	Uncertain significance (Jun 29, 2023)
8-70126855-G-T		not specified	Uncertain significance (Aug 05, 2023)
8-70126903-T-C		not specified	Uncertain significance (Apr 07, 2023)
8-70126947-C-T		not specified	Uncertain significance (Oct 05, 2021)
8-70126986-C-T		not specified	Uncertain significance (Dec 30, 2023)
8-70128448-A-G			Benign (Apr 06, 2018)
8-70128710-C-A		not specified	Uncertain significance (Nov 06, 2023)
8-70128799-C-T		not specified	Uncertain significance (Oct 06, 2021)
8-70128910-A-G		not specified	Uncertain significance (Oct 10, 2023)
8-70128911-C-T			Likely benign (May 21, 2018)
8-70128916-G-A		not specified	Uncertain significance (Dec 21, 2022)
8-70128935-T-C		not specified	Uncertain significance (Sep 27, 2022)
8-70131899-G-A		not specified	Uncertain significance (Feb 15, 2023)
8-70131997-G-A		not specified	Uncertain significance (Jul 20, 2021)
8-70131999-C-G		not specified	Uncertain significance (Dec 07, 2023)
8-70138257-G-A		not specified	Uncertain significance (Nov 01, 2022)
8-70138295-C-G		not specified	Uncertain significance (Nov 08, 2022)
8-70138313-C-T		not specified	Uncertain significance (Nov 30, 2022)
8-70138322-T-A		not specified	Uncertain significance (Apr 05, 2023)
8-70141210-G-A		not specified	Likely benign (Aug 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NCOA2	protein_coding	protein_coding	ENST00000452400	21	294044

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.04e-8	124649	0	5	124654	0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.29	622	805	0.773	0.0000422	9734
Missense in Polyphen		128	234.63	0.54553		2971
Synonymous	0.755	274	290	0.944	0.0000161	2786
Loss of Function	7.06	3	63.9	0.0469	0.00000317	731

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000177	0.0000177
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000331	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF- 2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK- ARNTL/BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:9430642}.
• Disease: DISEASE: Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N- terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation. {ECO:0000269|PubMed:12676584, ECO:0000269|PubMed:15657427, ECO:0000269|PubMed:9558366}.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Androgen receptor signaling pathway;Corticotropin-releasing hormone signaling pathway;Adipogenesis;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;Liver steatosis AOP;role of ppar-gamma coactivators in obesity and thermogenesis;Developmental Biology;Signal Transduction;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;Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3;RHO GTPases activate PKNs;HATs acetylate histones;RHO GTPase Effectors;Signaling by Rho GTPases;Glucocorticoid receptor regulatory network;Coregulation of Androgen receptor activity;Signaling by Nuclear Receptors;Chromatin organization;Estrogen-dependent gene expression;ESR-mediated signaling;Regulation of nuclear beta catenin signaling and target gene transcription;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: 0.317

Intolerance Scores

• rvis_EVS: -1.03
• rvis_percentile_EVS: 7.86

Haploinsufficiency Scores

• pHI: 0.930
• hipred: Y
• hipred_score: 0.786
• ghis: 0.626

Essentials

• essential_gene_CRISPR: E
• 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: Ncoa2
• Phenotype: embryo 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); growth/size/body region phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: ncoa2
• Affected structure: intersegmental vessel
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;regulation of glucose metabolic process;bile acid and bile salt transport;regulation of lipid metabolic process;response to progesterone;cellular response to hormone stimulus;circadian regulation of gene expression;locomotor rhythm;positive regulation of transcription by RNA polymerase II;cellular response to Thyroglobulin triiodothyronine
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear body;protein-containing complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding;chromatin binding;transcription coactivator activity;protein binding;nuclear receptor binding;aryl hydrocarbon receptor binding;protein domain specific binding;nuclear receptor transcription coactivator activity;thyroid hormone receptor coactivator activity;nuclear hormone receptor binding;protein dimerization activity