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GeneBe

RORC

RAR related orphan receptor C, the group of RAR related orphan receptors

Basic information

Region (hg38): 1:151806070-151831845

Links

ENSG00000143365OMIM:602943HGNC:10260Uniprot:P51449AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Moderate), mode of inheritance: AR
  • autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Supportive), mode of inheritance: AR
  • autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Immunodeficiency 42ARAllergy/Immunology/InfectiousIndiviiduals have been described as having increased susceptibility to mycobacterial and candidal infections, as well as disseminated mycobacterial infections after BCG vacciination, and awareness may allow preventive measures, and early and aggressive treatment of infectionsAllergy/Immunology/Infectious26160376

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RORC gene.

  • Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (236 variants)
  • not specified (19 variants)
  • Inborn genetic diseases (11 variants)
  • not provided (5 variants)
  • RORC-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RORC 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
clinvar
68
clinvar
6
clinvar
77
missense
108
clinvar
3
clinvar
2
clinvar
113
nonsense
1
clinvar
1
clinvar
1
clinvar
1
clinvar
4
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
2
clinvar
3
splice region
3
6
1
10
non coding
1
clinvar
29
clinvar
19
clinvar
49
Total 1 2 115 101 27

Variants in RORC

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

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

Position Type Phenotype Significance ClinVar
1-151807484-C-A Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Oct 07, 2018)646625
1-151807494-G-C Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Mar 23, 2022)1028332
1-151807498-C-T Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Mar 26, 2022)2117041
1-151807499-G-A Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Benign (Dec 06, 2023)1170508
1-151807517-C-T Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency • RORC-related condition Likely benign (Dec 19, 2023)1154072
1-151807539-G-A Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Sep 01, 2022)836560
1-151807540-C-T Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Mar 13, 2022)1924038
1-151807541-G-A Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Aug 03, 2021)744352
1-151807541-G-T Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Apr 30, 2020)1039273
1-151807544-T-C Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Oct 24, 2022)1419943
1-151807550-C-T Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Apr 06, 2023)2852811
1-151807552-C-T not specified • Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Aug 16, 2022)252645
1-151807561-G-A Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Aug 27, 2021)1020582
1-151807565-G-A Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (May 15, 2022)1895716
1-151807573-A-T Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Sep 10, 2018)640271
1-151807582-G-C Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Oct 13, 2022)1443781
1-151807602-C-G Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Jul 19, 2022)1009678
1-151807622-C-G Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Uncertain significance (Dec 11, 2023)1507227
1-151807623-T-C Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Benign (Jan 29, 2024)712886
1-151807625-G-C Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Oct 28, 2021)1586311
1-151807628-T-G Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Jan 22, 2023)1093843
1-151807637-G-C Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Sep 20, 2021)1605965
1-151807641-T-C Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Oct 28, 2023)1620714
1-151807653-G-T Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency Likely benign (Sep 20, 2022)2003786
1-151807701-C-T not specified Benign (Nov 12, 2023)2628172

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RORCprotein_codingprotein_codingENST00000318247 1125802
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.000.00015112521505321257470.00212
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.291923040.6310.00001833340
Missense in Polyphen26100.720.258131121
Synonymous-0.5081271201.060.000006811020
Loss of Function4.86129.50.03390.00000176299

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001560.00156
Ashkenazi Jewish0.0003970.000397
East Asian0.000.00
Finnish0.001060.000971
European (Non-Finnish)0.003710.00371
Middle Eastern0.000.00
South Asian0.001310.00131
Other0.001470.00147

dbNSFP

Source: dbNSFP

Function
FUNCTION: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively (PubMed:19965867, PubMed:22789990). Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue- selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC- mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A (PubMed:19965867). Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1 (PubMed:19965867). Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376). {ECO:0000250|UniProtKB:P51450, ECO:0000269|PubMed:19381306, ECO:0000269|PubMed:19965867, ECO:0000269|PubMed:20203100, ECO:0000269|PubMed:22789990, ECO:0000269|PubMed:26160376}.;
Disease
DISEASE: Immunodeficiency 42 (IMD42) [MIM:616622]: An autosomal recessive primary immunodeficiency characterized by increased susceptibility to concomitant candidiasis and mycobacteriosis. Candidiasis is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida. Mycobacteriosis is characterized by infections caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non- tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. IMD42 patients vaccinated with BCG are particularly at risk for developing disseminated mycobacterial infections. {ECO:0000269|PubMed:26160376}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Circadian rhythm - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);NHR;Nuclear Receptors;Interleukin-4 and 13 signaling;Transcriptional regulation by RUNX3;RUNX3 Regulates Immune Response and Cell Migration;Gene expression (Transcription);Transcriptional regulation by RUNX3;Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

pRec
0.0949

Intolerance Scores

loftool
0.0138
rvis_EVS
0.04
rvis_percentile_EVS
57.15

Haploinsufficiency Scores

pHI
0.675
hipred
Y
hipred_score
0.701
ghis
0.452

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.994

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rorc
Phenotype
hematopoietic 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); immune system phenotype; digestive/alimentary phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype;

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;xenobiotic metabolic process;regulation of glucose metabolic process;regulation of steroid metabolic process;cytokine-mediated signaling pathway;intracellular receptor signaling pathway;circadian regulation of gene expression;cellular response to sterol;positive regulation of circadian rhythm;steroid hormone mediated signaling pathway;regulation of fat cell differentiation;positive regulation of transcription, DNA-templated;adipose tissue development;regulation of transcription involved in cell fate commitment;T-helper 17 cell differentiation
Cellular component
nucleus;nucleoplasm;nuclear body
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;transcription coactivator binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;steroid hormone receptor activity;nuclear receptor activity;protein binding;oxysterol binding;zinc ion binding;ligand-activated transcription factor activity