NR1D2
nuclear receptor subfamily 1 group D member 2, the group of Nuclear receptor subfamily 1 group D
Basic information
Region (hg38): 3:23945286-23980637
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR1D2 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 | |||||
| missense | 31 | 33 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 31 | 3 | 1 |
Variants in NR1D2
This is a list of pathogenic ClinVar variants found in the NR1D2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-23945585-G-A | not specified | Uncertain significance (May 17, 2023) | ||
| 3-23954552-A-C | not specified | Uncertain significance (Jan 16, 2024) | ||
| 3-23954593-C-T | not specified | Uncertain significance (Aug 14, 2024) | ||
| 3-23954594-A-T | not specified | Uncertain significance (Nov 24, 2024) | ||
| 3-23954701-G-A | not specified | Uncertain significance (Dec 05, 2022) | ||
| 3-23954704-A-T | not specified | Uncertain significance (Aug 17, 2022) | ||
| 3-23954705-A-G | not specified | Likely benign (Sep 14, 2022) | ||
| 3-23954740-T-G | not specified | Uncertain significance (Jan 21, 2025) | ||
| 3-23954746-A-G | not specified | Likely benign (Mar 19, 2024) | ||
| 3-23956083-G-A | Likely benign (Jan 01, 2023) | |||
| 3-23956113-C-T | Benign (Dec 31, 2019) | |||
| 3-23959738-C-T | not specified | Uncertain significance (Nov 18, 2022) | ||
| 3-23961982-C-T | Familial atrioventricular septal defect | Likely pathogenic (Apr 08, 2016) | ||
| 3-23962061-G-T | not specified | Uncertain significance (Aug 22, 2023) | ||
| 3-23962081-C-A | not specified | Uncertain significance (Feb 05, 2025) | ||
| 3-23962115-C-G | not specified | Uncertain significance (Feb 19, 2025) | ||
| 3-23962123-C-T | not specified | Uncertain significance (Nov 18, 2022) | ||
| 3-23962148-A-G | not specified | Uncertain significance (Jan 17, 2025) | ||
| 3-23962169-A-G | not specified | Uncertain significance (Oct 11, 2024) | ||
| 3-23962170-C-G | not specified | Uncertain significance (Jun 06, 2023) | ||
| 3-23962184-C-T | not specified | Uncertain significance (Feb 07, 2025) | ||
| 3-23962228-G-T | not specified | Uncertain significance (Mar 06, 2023) | ||
| 3-23962259-A-G | not specified | Uncertain significance (Jan 04, 2025) | ||
| 3-23962277-A-G | not specified | Uncertain significance (May 04, 2022) | ||
| 3-23962292-G-A | not specified | Uncertain significance (Jul 30, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NR1D2 | protein_coding | protein_coding | ENST00000312521 | 8 | 35359 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00617 | 0.993 | 125732 | 0 | 15 | 125747 | 0.0000596 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.931 | 268 | 314 | 0.852 | 0.0000161 | 3899 |
| Missense in Polyphen | 64 | 111.78 | 0.57254 | 1332 | ||
| Synonymous | -1.13 | 120 | 105 | 1.14 | 0.00000516 | 1032 |
| Loss of Function | 2.93 | 8 | 23.2 | 0.344 | 0.00000126 | 296 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000164 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000881 | 0.0000879 |
| Middle Eastern | 0.000164 | 0.000163 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle. {ECO:0000269|PubMed:17892483, ECO:0000269|PubMed:17996965}.;
- Pathway
- NHR;Nuclear Receptors;Exercise-induced Circadian Regulation;Gene expression (Transcription);Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription
(Consensus)
Recessive Scores
- pRec
- 0.158
Intolerance Scores
- loftool
- 0.121
- rvis_EVS
- 0.09
- rvis_percentile_EVS
- 60.57
Haploinsufficiency Scores
- pHI
- 0.230
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.505
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nr1d2
- Phenotype
- homeostasis/metabolism 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;transcription initiation from RNA polymerase II promoter;multicellular organism development;hormone-mediated signaling pathway;regulation of lipid metabolic process;cell differentiation;intracellular receptor signaling pathway;response to lipid;regulation of circadian rhythm;steroid hormone mediated signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;rhythmic process;regulation of inflammatory response;lipid homeostasis;energy homeostasis;regulation of skeletal muscle cell differentiation
- Cellular component
- nucleus;nucleoplasm;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;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;steroid hormone receptor activity;nuclear receptor activity;protein binding;transcription factor binding;zinc ion binding;nuclear receptor transcription coactivator activity;signaling receptor activity