NR1H3

nuclear receptor subfamily 1 group H member 3, the group of Nuclear receptor subfamily 1 group H

Basic information

Region (hg38): 11:47248299-47269033

Links

ENSG00000025434 ∙ NCBI:10062 ∙ OMIM:602423 ∙ HGNC:7966 ∙ Uniprot:Q13133 ∙ 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 NR1H3 gene.

• Inborn genetic diseases (13 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR1H3 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				2		2
missense			12		1	13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1		2
Total	0	0	13	3	1

Variants in NR1H3

This is a list of pathogenic ClinVar variants found in the NR1H3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-47248680-G-C		not specified	Uncertain significance (Jul 25, 2023)
11-47248704-C-T			Benign (Oct 26, 2015)
11-47248758-G-T		not specified	Uncertain significance (Feb 06, 2024)
11-47248762-G-A			Likely benign (Jul 17, 2018)
11-47259253-C-T		not specified	Likely benign (Nov 06, 2023)
11-47259814-C-A		not specified	Uncertain significance (May 18, 2022)
11-47259826-G-C		not specified	Uncertain significance (Dec 21, 2023)
11-47259833-G-A		not specified	Uncertain significance (Aug 12, 2021)
11-47259902-G-T			Benign (Dec 31, 2019)
11-47260427-G-A		not specified	Uncertain significance (Jan 09, 2024)
11-47260509-T-C			Likely benign (Jun 23, 2018)
11-47260552-G-A		not specified	Uncertain significance (Nov 05, 2021)
11-47260569-C-T			Likely benign (Apr 11, 2018)
11-47260651-C-T		not specified	Uncertain significance (Aug 19, 2023)
11-47261296-A-T		not specified	Uncertain significance (Jan 04, 2024)
11-47261316-T-C		not specified	Uncertain significance (Nov 03, 2023)
11-47261318-C-T		not specified	Uncertain significance (Jun 28, 2023)
11-47261577-C-T		not specified	Uncertain significance (Aug 16, 2022)
11-47261686-G-A		not specified	Uncertain significance (Dec 03, 2021)
11-47261704-T-C		not specified	Uncertain significance (Nov 17, 2022)
11-47261941-G-A		not specified	Uncertain significance (Dec 07, 2021)
11-47261964-A-C		not specified	Uncertain significance (Feb 10, 2022)
11-47262000-G-A		not specified	Uncertain significance (Jan 23, 2024)
11-47267939-A-G		not specified	Uncertain significance (Jun 22, 2023)
11-47268573-G-C		not specified	Uncertain significance (Dec 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NR1H3	protein_coding	protein_coding	ENST00000467728	9	20546

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.904	0.0963	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	222	283	0.783	0.0000180	2915
Missense in Polyphen		63	119.64	0.52657		1226
Synonymous	1.23	93	109	0.850	0.00000653	899
Loss of Function	3.61	3	20.8	0.144	0.00000100	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000706	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:19481530, PubMed:25661920). Interaction with retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES (By similarity). LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides (By similarity). Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (PubMed:19481530). Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). {ECO:0000250|UniProtKB:Q9Z0Y9, ECO:0000269|PubMed:19481530, ECO:0000269|PubMed:25661920}.
• Pathway: Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);NHR;Nuclear Receptors;SREBF and miR33 in cholesterol and lipid homeostasis;White fat cell differentiation;Adipogenesis;Liver X Receptor Pathway;PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Angiopoietin Like Protein 8 Regulatory Pathway;PPAR signaling pathway;Steatosis AOP;White fat cell differentiation;Gene expression (Transcription);mechanism of gene regulation by peroxisome proliferators via ppara;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: 0.542

Intolerance Scores

• loftool: 0.0639
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.44

Haploinsufficiency Scores

• pHI: 0.957
• hipred: Y
• hipred_score: 0.662
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nr1h3
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system 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); normal phenotype; reproductive system phenotype; hematopoietic 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); 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); cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: nr1h3
• Affected structure: ceratohyal cartilage
• Phenotype tag: abnormal
• Phenotype quality: curved

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 receptor biosynthetic process;positive regulation of cholesterol efflux;negative regulation of cholesterol storage;cell differentiation;intracellular receptor signaling pathway;positive regulation of cellular protein metabolic process;negative regulation of lipid transport;positive regulation of cholesterol transport;response to progesterone;positive regulation of toll-like receptor 4 signaling pathway;cholesterol homeostasis;regulation of circadian rhythm;negative regulation of macrophage activation;apoptotic cell clearance;steroid hormone mediated signaling pathway;positive regulation of fatty acid biosynthetic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of pinocytosis;negative regulation of inflammatory response;positive regulation of lipoprotein lipase activity;lipid homeostasis;sterol homeostasis;negative regulation of interferon-gamma-mediated signaling pathway;triglyceride homeostasis;cellular response to lipopolysaccharide;negative regulation of pancreatic juice secretion;negative regulation of secretion of lysosomal enzymes;negative regulation of cold-induced thermogenesis;regulation of nuclear receptor transcription coactivator activity
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm;receptor complex;RNA polymerase II transcription factor complex
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;steroid hormone receptor activity;transcription coactivator activity;nuclear receptor activity;protein binding;transcription factor binding;zinc ion binding;cholesterol binding;nuclear receptor transcription coactivator activity;sterol response element binding;signaling receptor activity;transcription regulatory region DNA binding