NR1H2

nuclear receptor subfamily 1 group H member 2, the group of Nuclear receptor subfamily 1 group H

Basic information

Region (hg38): 19:50329652-50383388

Previous symbols: [ "UNR" ]

Links

ENSG00000131408 ∙ NCBI:7376 ∙ OMIM:600380 ∙ HGNC:7965 ∙ Uniprot:P55055 ∙ 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 NR1H2 gene.

• Inborn genetic diseases (24 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR1H2 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						0
missense			3			3
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			22		2	24
Total	0	0	25	0	2

Variants in NR1H2

This is a list of pathogenic ClinVar variants found in the NR1H2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-50358590-C-A		not specified	Uncertain significance (Aug 21, 2023)
19-50358594-G-C			Benign (Jan 19, 2018)
19-50358606-G-C		not specified	Uncertain significance (Dec 16, 2022)
19-50358747-C-A		not specified	Uncertain significance (Dec 12, 2023)
19-50359054-C-G		not specified	Uncertain significance (Jun 27, 2022)
19-50359058-G-A		not specified	Uncertain significance (Nov 21, 2022)
19-50359508-C-T		not specified	Uncertain significance (Oct 05, 2021)
19-50359531-A-G		not specified	Uncertain significance (Apr 07, 2022)
19-50359576-A-G		not specified	Uncertain significance (Aug 10, 2021)
19-50359609-C-T		not specified	Uncertain significance (Apr 22, 2022)
19-50359631-C-T		not specified	Uncertain significance (Feb 10, 2022)
19-50359744-C-T		not specified	Uncertain significance (Aug 11, 2022)
19-50359764-G-A		not specified	Uncertain significance (Mar 02, 2023)
19-50359783-C-T		not specified	Uncertain significance (Aug 10, 2021)
19-50359803-T-C		not specified	Uncertain significance (Apr 22, 2022)
19-50359817-C-T			Benign (Jan 19, 2018)
19-50359840-C-G		not specified	Uncertain significance (May 26, 2022)
19-50361000-C-A		Myoepithelial tumor	Uncertain significance (Nov 01, 2022)
19-50361058-T-C		not specified	Uncertain significance (Feb 07, 2023)
19-50361063-A-T		not specified	Uncertain significance (Feb 07, 2023)
19-50361101-C-A		not specified	Uncertain significance (Dec 08, 2023)
19-50361677-C-T		not specified	Uncertain significance (Jul 06, 2021)
19-50361698-G-A		not specified	Uncertain significance (May 04, 2022)
19-50361712-T-A		not specified	Uncertain significance (Feb 16, 2023)
19-50361718-G-A		not specified	Uncertain significance (Aug 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NR1H2	protein_coding	protein_coding	ENST00000253727	8	53330

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.375	0.625	125194	0	12	125206	0.0000479

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.889	260	304	0.856	0.0000209	2934
Missense in Polyphen		60	101.74	0.58972		964
Synonymous	-2.49	169	133	1.27	0.00000978	933
Loss of Function	3.39	5	22.2	0.225	0.00000112	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000942	0.0000922
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000550
Finnish	0.00	0.00
European (Non-Finnish)	0.0000647	0.0000617
Middle Eastern	0.0000556	0.0000550
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920). Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP- dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). 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). {ECO:0000250|UniProtKB:Q60644, ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:25661920}.
• Pathway: Insulin resistance - Homo sapiens (human);NHR;Nuclear Receptors;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Steatosis AOP;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;VLDLR internalisation and degradation;Plasma lipoprotein clearance;Transport of small molecules;Plasma lipoprotein assembly, remodeling, and clearance;RXR and RAR heterodimerization with other nuclear receptor (Consensus)

Recessive Scores

• pRec: 0.754

Intolerance Scores

• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.51

Haploinsufficiency Scores

• pHI: 0.797
• hipred: Y
• hipred_score: 0.740
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.996

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nr1h2
• 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); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; reproductive system phenotype; normal 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); 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); hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton 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)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;lipid metabolic process;multicellular organism development;negative regulation of macrophage derived foam cell differentiation;positive regulation of triglyceride biosynthetic process;positive regulation of cholesterol efflux;positive regulation of lipid storage;negative regulation of cholesterol storage;cell differentiation;positive regulation of cellular protein metabolic process;negative regulation of lipid transport;positive regulation of cholesterol transport;cholesterol homeostasis;steroid hormone mediated signaling pathway;cellular lipid metabolic process;positive regulation of fatty acid biosynthetic process;negative regulation of proteolysis;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;retinoic acid receptor signaling pathway;negative regulation of pinocytosis;positive regulation of lipoprotein lipase activity;lipid homeostasis;negative regulation of interferon-gamma-mediated signaling pathway;cellular response to lipopolysaccharide;positive regulation of high-density lipoprotein particle assembly;positive regulation of pancreatic juice secretion;positive regulation of secretion of lysosomal enzymes;negative regulation of cold-induced thermogenesis
• Cellular component: nucleus;nucleoplasm;cytoplasm;RNA polymerase II transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;steroid hormone receptor activity;nuclear receptor activity;protein binding;transcription factor binding;zinc ion binding;nuclear receptor transcription coactivator activity;apolipoprotein A-I receptor binding;signaling receptor activity;retinoid X receptor binding;ATPase binding