NR5A2

nuclear receptor subfamily 5 group A member 2, the group of Nuclear receptor subfamily 5 group A

Basic information

Region (hg38): 1:200027613-200177420

Previous symbols: [ "FTF" ]

Links

ENSG00000116833 ∙ NCBI:2494 ∙ OMIM:604453 ∙ HGNC:7984 ∙ Uniprot:O00482 ∙ 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 NR5A2 gene.

• Inborn genetic diseases (16 variants)
• not provided (4 variants)
• not specified (1 variants)
• Premature ovarian failure (1 variants)
• Anophthalmia-microphthalmia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR5A2 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	1	2
missense			14	2		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	14	3	2

Variants in NR5A2

This is a list of pathogenic ClinVar variants found in the NR5A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-200039674-C-T			Likely benign (May 14, 2018)
1-200039789-A-G		not specified	Uncertain significance (Jan 11, 2023)
1-200045454-G-A			Benign (May 14, 2018)
1-200048167-A-C			Likely benign (Aug 15, 2018)
1-200048174-G-A		not specified	Uncertain significance (Oct 25, 2023)
1-200048273-A-C		not specified	Uncertain significance (Aug 12, 2021)
1-200048389-T-G		Premature ovarian failure • not specified	Conflicting classifications of pathogenicity (Aug 16, 2021)
1-200048439-C-G		not specified	Uncertain significance (Mar 23, 2022)
1-200048445-G-A		not specified	Uncertain significance (Dec 15, 2021)
1-200048464-C-G		not specified	Uncertain significance (Dec 14, 2023)
1-200048478-G-T		not specified	Uncertain significance (Aug 30, 2021)
1-200048501-C-G		not specified	Uncertain significance (Feb 17, 2024)
1-200048507-C-T		not specified	Uncertain significance (Mar 01, 2023)
1-200048556-C-T		not specified	Uncertain significance (Nov 09, 2021)
1-200048592-C-T		Anophthalmia-microphthalmia syndrome	Likely benign (Jan 01, 2013)
1-200048613-C-A		not specified	Uncertain significance (Mar 27, 2023)
1-200048706-G-A		not specified	Uncertain significance (Jun 22, 2021)
1-200048706-G-C		not specified	Benign/Likely benign (Jun 22, 2021)
1-200048714-C-G		not specified	Uncertain significance (Jun 09, 2022)
1-200048760-A-T		Long QT syndrome	Likely benign (-)
1-200048796-G-A		not specified	Uncertain significance (Sep 30, 2021)
1-200111232-T-C		not specified	Uncertain significance (Sep 22, 2023)
1-200111336-C-CAA		not specified	Benign (Mar 29, 2016)
1-200120881-T-C		not specified	Uncertain significance (May 04, 2022)
1-200120898-C-T		not specified	Uncertain significance (Oct 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NR5A2	protein_coding	protein_coding	ENST00000367362	8	149823

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.238	0.762	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	222	288	0.771	0.0000148	3556
Missense in Polyphen		22	64.922	0.33887		790
Synonymous	-0.601	117	109	1.07	0.00000577	1020
Loss of Function	3.82	7	29.3	0.239	0.00000181	298

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000506	0.000489
Ashkenazi Jewish	0.00	0.00
East Asian	0.000561	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000107	0.000105
Middle Eastern	0.000561	0.000544
South Asian	0.00	0.00
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957). Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha- hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. {ECO:0000269|PubMed:15707893, ECO:0000269|PubMed:15723037, ECO:0000269|PubMed:15897460, ECO:0000269|PubMed:16289203, ECO:0000269|PubMed:20159957}.
• Pathway: Maturity onset diabetes of the young - Homo sapiens (human);NHR;Nuclear Receptors;Steatosis AOP;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

• pRec: 0.405

Intolerance Scores

• loftool: 0.0846
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• pHI: 0.922
• hipred: Y
• hipred_score: 0.875
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nr5a2
• Phenotype: embryo phenotype; liver/biliary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); reproductive system phenotype; digestive/alimentary phenotype; immune system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: nr5a2
• Affected structure: cranial cartilage
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;bile acid metabolic process;hormone-mediated signaling pathway;embryo development ending in birth or egg hatching;tissue development;intracellular receptor signaling pathway;epithelial cell differentiation;regulation of cell population proliferation;homeostatic process;cholesterol homeostasis;steroid hormone mediated signaling pathway;positive regulation of viral genome replication;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;pancreas morphogenesis;calcineurin-mediated signaling;cellular response to leukemia inhibitory factor
• Cellular component: nucleus;nucleoplasm;cytoplasm;RNA polymerase II transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;steroid hormone receptor activity;nuclear receptor activity;protein binding;phospholipid binding;zinc ion binding;sequence-specific DNA binding;transcription regulatory region DNA binding