NR5A2

protein-coding

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

Gene summary

The protein encoded by this gene is a DNA-binding zinc finger transcription factor and is a member of the fushi tarazu factor-1 subfamily of orphan nuclear receptors. The encoded protein is involved in the expression of genes for hepatitis B virus and cholesterol biosynthesis, and may be an important regulator of embryonic development. [provided by RefSeq, Jun 2016]

Previous symbols:

MANE transcript

NM_205860.3

Inheritance

—

ClinVar variants

P:1U:53B:5

Top phenotype

Premature ovarian failure

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr1:200,027,614-200,177,420

External References & Databases

Ensembl (ENSG00000116833)

Transcript & Mutation Effects

hg38 • Region Span ~149.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NR5A2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 3

Premature ovarian failureTotal: 1

Anophthalmia-microphthalmia syndromeTotal: 1

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_205860.3. 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			1 clinvar	1 clinvar	1 clinvar	3
missense		1 clinvar	51 clinvar	3 clinvar		55
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	53	4	1	59

Highest pathogenic variant AF is 0.000009912657

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_205860.3	RefSeq	NP_995582.1	8	MANE Select
ENST00000367362.8	Ensembl	ENSP00000356331.3	8	MANE Select
NM_001276464.2	RefSeq	NP_001263393.1	6	Standard
NM_003822.5	RefSeq	NP_003813.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nr5a2	Danio rerio	Structure: cranial cartilage Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

nr5a2

Danio rerio

Structure: cranial cartilage

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Maturity onset diabetes of the young - Homo sapiens (human)
NHR
Nuclear Receptors
Steatosis AOP
Gene expression (Transcription)

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

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

Cellular Component

nucleus
nucleoplasm
cytoplasm
RNA polymerase II transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367362
Coding exons: 8
Length: 149823
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.38	222	288	0.771	0.0000148	3556
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00045	0.00043	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00056	0.00054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.405

Intolerance Scores

LoFtool: 0.0846
RVIS EVS: -0.29
RVIS percentile EVS: 33.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.962

Gene Damage Prediction

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