NR1D1
nuclear receptor subfamily 1 group D member 1, the group of Nuclear receptor subfamily 1 group D
Basic information
Region (hg38): 17:40092793-40100589
Previous symbols: [ "THRAL" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Congenital nongoitrous hypothyroidism 6 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NR1D1 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 | |||||
| missense | 27 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 4 | |||||
| Total | 1 | 0 | 31 | 1 | 2 |
Variants in NR1D1
This is a list of pathogenic ClinVar variants found in the NR1D1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-40093023-A-T | Inborn genetic diseases | Uncertain significance (Aug 10, 2021) | ||
| 17-40093039-C-T | Congenital nongoitrous hypothyroidism 6 | Uncertain significance (Sep 23, 2021) | ||
| 17-40093060-C-T | Inborn genetic diseases | Uncertain significance (Jun 15, 2021) | ||
| 17-40093099-C-T | not specified | Uncertain significance (Dec 27, 2023) | ||
| 17-40093178-G-A | not specified | Uncertain significance (Nov 03, 2022) | ||
| 17-40093196-G-A | not specified | Uncertain significance (Jan 30, 2024) | ||
| 17-40093275-C-T | Congenital nongoitrous hypothyroidism 6 | Uncertain significance (Mar 18, 2016) | ||
| 17-40093295-C-T | Uncertain significance (Dec 01, 2023) | |||
| 17-40093323-T-TC | Congenital nongoitrous hypothyroidism 6 | Pathogenic (Oct 01, 2021) | ||
| 17-40093921-C-A | not specified | Uncertain significance (Jan 08, 2024) | ||
| 17-40093972-A-C | not specified | Uncertain significance (Jan 07, 2022) | ||
| 17-40094038-C-G | not specified | Uncertain significance (Feb 11, 2022) | ||
| 17-40094988-G-A | not specified | Uncertain significance (Aug 28, 2023) | ||
| 17-40095042-A-G | not specified | Uncertain significance (Aug 17, 2021) | ||
| 17-40095127-G-A | Likely benign (Apr 10, 2018) | |||
| 17-40095446-G-T | not specified | Uncertain significance (May 25, 2023) | ||
| 17-40095482-T-C | not specified | Uncertain significance (May 14, 2024) | ||
| 17-40095497-C-T | not specified | Likely benign (Mar 21, 2022) | ||
| 17-40095505-G-A | not specified | Uncertain significance (Nov 14, 2023) | ||
| 17-40095626-T-C | not specified | Uncertain significance (Feb 15, 2023) | ||
| 17-40095630-G-A | Benign (Apr 24, 2018) | |||
| 17-40095638-T-C | not specified | Uncertain significance (Dec 06, 2021) | ||
| 17-40095643-C-T | not specified | Uncertain significance (Sep 22, 2023) | ||
| 17-40095745-G-A | not specified | Uncertain significance (Dec 01, 2022) | ||
| 17-40095748-T-C | not specified | Uncertain significance (Oct 26, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NR1D1 | protein_coding | protein_coding | ENST00000246672 | 8 | 7939 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.818 | 0.182 | 125738 | 0 | 10 | 125748 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.38 | 311 | 387 | 0.803 | 0.0000253 | 3999 |
| Missense in Polyphen | 67 | 139.34 | 0.48085 | 1363 | ||
| Synonymous | -1.64 | 187 | 161 | 1.16 | 0.0000105 | 1290 |
| Loss of Function | 3.69 | 4 | 23.2 | 0.172 | 0.00000131 | 236 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000904 | 0.0000904 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000467 | 0.0000462 |
| European (Non-Finnish) | 0.0000362 | 0.0000352 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000168 | 0.000163 |
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 ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage 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 nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner. {ECO:0000269|PubMed:12021280, ECO:0000269|PubMed:15761026, ECO:0000269|PubMed:16968709, ECO:0000269|PubMed:18006707, ECO:0000269|PubMed:19710360, ECO:0000269|PubMed:1971514, ECO:0000269|PubMed:21479263, ECO:0000269|PubMed:22184247, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:2539258}.;
- Pathway
- Circadian rhythm - Homo sapiens (human);NHR;Circadian Clock;BMAL1-CLOCK,NPAS2 activates circadian gene expression;RORA activates gene expression;NR1D1 (REV-ERBA) represses gene expression;Gene expression (Transcription);Circadian Clock;Generic Transcription Pathway;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;NR1D1 (REV-ERBA) represses gene expression;Circadian rhythm pathway
(Consensus)
Recessive Scores
- pRec
- 0.201
Intolerance Scores
- loftool
- 0.0399
- rvis_EVS
- -0.78
- rvis_percentile_EVS
- 12.97
Haploinsufficiency Scores
- pHI
- 0.317
- hipred
- Y
- hipred_score
- 0.750
- ghis
- 0.532
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Nr1d1
- Phenotype
- growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; vision/eye phenotype; reproductive 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); 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); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail 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);
Zebrafish Information Network
- Gene name
- nr1d1
- Affected structure
- liver
- Phenotype tag
- abnormal
- Phenotype quality
- increased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;glycogen biosynthetic process;transcription initiation from RNA polymerase II promoter;multicellular organism development;circadian rhythm;hormone-mediated signaling pathway;proteasomal protein catabolic process;negative regulation of receptor biosynthetic process;regulation of lipid metabolic process;cell differentiation;intracellular receptor signaling pathway;circadian regulation of gene expression;response to lipid;negative regulation of toll-like receptor 4 signaling pathway;regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter;cholesterol homeostasis;regulation of circadian rhythm;steroid hormone mediated signaling pathway;response to leptin;regulation of fat cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;circadian temperature homeostasis;regulation of insulin secretion involved in cellular response to glucose stimulus;regulation of type B pancreatic cell proliferation;positive regulation of bile acid biosynthetic process;cellular response to lipopolysaccharide;negative regulation of cold-induced thermogenesis
- Cellular component
- nuclear chromatin;nucleus;nucleoplasm;cytoplasm;nuclear body;dendrite;dendritic spine;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;transcription corepressor binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;steroid hormone receptor activity;transcription corepressor activity;nuclear receptor activity;protein binding;transcription factor binding;zinc ion binding;heme binding;nuclear receptor transcription coactivator activity;signaling receptor activity;transcription regulatory region DNA binding;E-box binding