NR1D1

Summary

NR1D1 (nuclear receptor subfamily 1 group D member 1, HGNC:7962) is a protein-coding gene on chromosome 17q21.1, encoding Nuclear receptor subfamily 1 group D member 1 (P20393). Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner.

This gene encodes a transcription factor that is a member of the nuclear receptor subfamily 1. The encoded protein is a ligand-sensitive transcription factor that negatively regulates the expression of core clock proteins. In particular this protein represses the circadian clock transcription factor aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL). This protein may also be involved in regulating genes that function in metabolic, inflammatory and cardiovascular processes.

Source: NCBI Gene 9572 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 87 total — 1 pathogenic
• Druggable target: yes
• Transcription factor: yes — 29 downstream targets (CollecTRI)
• MANE Select transcript: NM_021724

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7962
Approved symbol	NR1D1
Name	nuclear receptor subfamily 1 group D member 1
Location	17q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ear-1, hRev, Rev-ErbAalpha, THRA1, REVERBA, REVERBalpha
Ensembl gene	ENSG00000126368
Ensembl biotype	protein_coding
OMIM	602408
Entrez	9572

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000246672

RefSeq mRNA: 1 — MANE Select: NM_021724 NM_021724

CCDS: CCDS11361

Canonical transcript exons

ENST00000246672 — 8 exons

Exon	Start	End
ENSE00000720300	40095444	40096087
ENSE00000863341	40093912	40094122
ENSE00000863343	40096691	40096779
ENSE00000863344	40097065	40097403
ENSE00001058054	40100064	40100589
ENSE00001310461	40092793	40093282
ENSE00001718983	40096443	40096587
ENSE00002342460	40094935	40095120

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.4357 / max 1198.0044, expressed in 1751 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165668	12.7304	1401
165671	2.8261	1177
165667	2.5634	655
165673	1.5369	839
165672	1.4759	807
165669	0.5666	254
165666	0.2923	168
165665	0.1873	90
165670	0.1527	60
165664	0.1041	33

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	98.62	gold quality
skin of abdomen	UBERON:0001416	97.73	gold quality
pancreatic ductal cell	CL:0002079	97.43	gold quality
zone of skin	UBERON:0000014	96.87	gold quality
right lung	UBERON:0002167	96.05	gold quality
ectocervix	UBERON:0012249	95.95	gold quality
tibialis anterior	UBERON:0001385	95.79	silver quality
paraflocculus	UBERON:0005351	95.61	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.40	gold quality
nipple	UBERON:0002030	95.30	gold quality
cervix squamous epithelium	UBERON:0006922	95.26	gold quality
endothelial cell	CL:0000115	95.23	gold quality
cerebellar hemisphere	UBERON:0002245	94.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.95	gold quality
cerebellar cortex	UBERON:0002129	94.93	gold quality
gastrocnemius	UBERON:0001388	94.83	gold quality
type B pancreatic cell	CL:0000169	94.55	gold quality
cerebellum	UBERON:0002037	94.50	gold quality
endocervix	UBERON:0000458	94.41	gold quality
cartilage tissue	UBERON:0002418	94.40	gold quality
muscle of leg	UBERON:0001383	94.25	gold quality
olfactory bulb	UBERON:0002264	94.25	gold quality
tibial artery	UBERON:0007610	94.21	gold quality
popliteal artery	UBERON:0002250	94.20	gold quality
cardia of stomach	UBERON:0001162	94.14	gold quality
mucosa of stomach	UBERON:0001199	94.13	gold quality
left adrenal gland cortex	UBERON:0035825	93.55	gold quality
diaphragm	UBERON:0001103	93.51	gold quality
apex of heart	UBERON:0002098	93.49	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	131.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

29 targets.

Target	Regulation
AFP	Unknown
APOA1	Unknown
APOC3	Unknown
BMAL1	Repression
CCL2
CDKN1A	Unknown
CLOCK	Unknown
CRX	Activation
CYP7A1	Unknown
DRD3	Unknown
FGF21	Repression
G6PC1	Unknown
GJA1	Repression
IL6	Repression
NPAS2	Repression
NR1D1	Repression
NRL	Activation
NUPR1	Activation
PCK1	Repression
PPARG	Repression
PPARGC1A	Repression
PTGS2	Activation
RARRES2	Activation
RCVRN	Repression
RGR	Repression
RORC	Repression
SERPINE1	Unknown
TLR4	Repression
TSHB	Repression

JASPAR motifs

Motif	Name	Family
MA1531.1	NR1D1	Thyroid hormone receptor-related factors (NR1)
MA1531.2	NR1D1	Thyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:14559106

Upstream regulators (CollecTRI, top): BHLHE41, BMAL1, CLOCK, ESRRA, MYC, NR1D1, NR1D2, NR1H3, NR3C1, PPARA, PPARG, PPARGC1A, RORA, TP53

miRNA regulators (miRDB)

51 targeting NR1D1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-5004-3P	99.54	68.27	1371

Literature-anchored findings (GeneRIF, showing 40)

• novel physiological role for members of the Rev-erb family of nuclear receptors in the regulation of genes involved in triglyceride metabolism and the pathogenesis of atherosclerosis (PMID:12021280)
• ROR(alpha) and Reverb(alpha) are expressed with a similar tissue distribution and are both induced during the differentiation of rat L6 myoblastic cells (PMID:12114512)
• hRev-erbalpha plays a key role in hRORalpha1 action (PMID:12377782)
• Data show that Rev-erb alpha and beta contain a functional nuclear location signal in the DNA-binding domain, and suggest that they control their intracellular localization via a mechanism different from that of other nuclear receptors. (PMID:12683943)
• Rev-Erbalpha as a target gene of PPARgamma in adipose tissue and demonstrate a role for this nuclear receptor as a promoter of adipocyte differentiation. (PMID:12821652)
• Overexpression of EAR1 upregulated expression of IL6 and COX2, and increased transactivation by NFKB and nuclear translocation of p65 in A7r5 VSMCs. The expression of EAR1 was upregulated by RORalpha1 but that upregulation was attenuated by EAR1 itself (PMID:15013753)
• the N-CoR/HDAC3 complex has a role in regulating the expression of genes involved in circadian rhythm by functioning as corepressor for Rev-erbalpha (PMID:15761026)
• findings show that GSK3beta phosphorylates and stabilizes Rev-erbalpha, a negative component of the circadian clock; control of Rev-erbalpha protein stability is a critical component of the peripheral clock and a biological target of lithium therapy (PMID:16484495)
• Rev-ErbAalpha is highly expressed in osteoarthritis articular chondrocytes and that its expression is modulated by known cartilage catabolic and anabolic stimuli (PMID:17075855)
• findings show that rev-erbalpha serves as a heme sensor that coordinates the cellular clock, glucose homeostasis, and energy metabolism (PMID:18006707)
• heme regulation of REV-ERBs may link the control of metabolism and the mammalian clock (PMID:18037887)
• Rev-erbalpha protein levels must rise and then fall for adipocyte differentiation to occur. Stable expression of Rev-erb protein prevents induction of PPARgamma2. (PMID:18227153)
• These data identify Rev-erbalpha as a new LXR target gene, inhibiting LXR-induction of TLR-4 in a negative transcriptional feedback loop, but not cholesterol homeostasis gene expression. (PMID:18511497)
• This study suggests that NR1D1 does not play a major role in the pathophysiology of mood disorders in the Japanese population. (PMID:18804497)
• This study indicated a nominal association of the REV-ERBalpha gene with bipolar disorder, suggest a possible role of REV-ERBalpha in the pathogenesis of bipolar disorder. (PMID:19267705)
• Review. We propose that the nuclear receptor and core clock component Rev-erb-alpha behaves as a gatekeeper to timely coordinate the circadian metabolic response. (PMID:19696364)
• Rev-erbalpha modulates the synthesis of its own ligand in a negative feedback pathway that maintains heme levels and regulates cellular energy metabolism. (PMID:19710360)
• While negative, our findings do not exclude an involvement of DGKH and NR1D1 in lithium prophylaxis. (PMID:19818381)
• Results show that the cells of this aggressive form of breast cancer are genetically preprogrammed to depend on NR1D1 and PBP for the energy production necessary for survival. (PMID:20160030)
• Arf-bp1 and Pam are novel regulators of circadian gene expression that target Rev-erb alpha for degradation (PMID:20534529)
• Study reports the crystal structure of a nuclear receptor-co-repressor (N-CoR) interaction domain 1 (ID1) peptide bound to truncated human Rev-erbalpha ligand-binding domain. (PMID:20581824)
• Data demonstrate that NPAS2 is also a RORalpha and REV-ERBalpha target gene. (PMID:20817722)
• REV-ERBalpha plays a dual role in regulation of the activity of the BMAL1/CLOCK heterodimer by regulation of expression of both the BMAL1 and CLOCK genes. (PMID:21479263)
• in situ hybridization revealed that RORA and NR1D1 were expressed in human endometrial stromal and epithelial cells (PMID:22024429)
• Thyroid hormone receptor-alpha/NR1D1 polymorphisms were not associated with baseline characteristics, including serum TSH and free thyroxine. None of the polymorphisms were associated with bone mineral density or osteoporotic fractures. (PMID:22224817)
• Genetic variants of NR1D1 associate with bipolar disorder. (PMID:22538398)
• A haplotype block in REV-ERBalpha was associated with white matter lesion volumes in the Rotterdam Study I. (PMID:23083441)
• DBC1 modulates the stability and function of the nuclear receptor Rev-erb-alpha. (PMID:23398316)
• Rev-erbalpha bestows protection against mycobacterial infection by direct gene repression of IL10 and thus provide a novel target in modulating macrophage microbicidal properties. (PMID:23449984)
• apoA-IV inhibits hepatic gluconeogenesis by decreasing Glc-6-Pase and PEPCK gene expression through NR1D1. (PMID:24311788)
• Rev-erbalpha is a novel regulator of hepatic stellate cell transdifferentation (PMID:24497272)
• Using free-energy simulations, the study shows that rev-erbA-alpha-induced DNA deformation preferentially occurs by induced fit rather than by conformational selection, even though the DNA is only slightly distorted in the complex. (PMID:24677802)
• Our results suggest that the REV-ERB ALPHA rs939347 polymorphism could modulate body fat mass in men. The present work supports the role of REV-ERB ALPHA in the development of obesity as well as a potential target for the treatment of obesity (PMID:25089907)
• CRY2 and REV-ERB ALPHA as the clock genes upregulated in obesity during the 24 h period and that REV-ERB ALPHA is an important gene associated with MS. (PMID:25365257)
• associations between NR1D1, RORA and RORB genes and bipolar disorder.( (PMID:25789810)
• the role of NR1D1 polymorphisms in the regulation of Nuclear receptor REV-ERBalpha and circadian rhythms regulation (PMID:25798852)
• Highly quantitative fluorescence anisotropy assays in competition mode revealed that the rev-erbA-alpha specificity for the NCoR corepressor lies in the first two residues of the beta-strand in Interaction Domain 1 of NCoR. (PMID:25969949)
• Data show that ubiquitin E3 ligase Siah2 depletion delays circadian degradation of nuclear hormone receptor RevErbalpha (Nr1d1) and lengthens period length. (PMID:26392558)
• NR1D1 and BMAL1 mRNA and protein levels were significantly reduced in OA compared to normal cartilage. In cultured human chondrocytes, a clear circadian rhythmicity was observed for NR1D1 and BMAL1. (PMID:27884645)
• Downregulation of NR1D1 in MCF7 cells resulted in resistance to doxorubicin, both in vitro and in vivo Analysis of four public patient data sets indicated that NR1D1 expression correlates positively with clinical outcome in breast cancer patients who received chemotherapy. Our findings suggest that NR1D1 and its ligands provide therapeutic options that could enhance the outcomes of chemotherapy in breast cancer patients (PMID:28249904)

Cross-species orthologs

188 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr1d1	ENSDARG00000033160
mus_musculus	Nr1d1	ENSMUSG00000020889
rattus_norvegicus	Nr1d1	ENSRNOG00000009329
drosophila_melanogaster	EcR	FBGN0000546
drosophila_melanogaster	Hr96	FBGN0015240
caenorhabditis_elegans		WBGENE00001062
caenorhabditis_elegans	nhr-2	WBGENE00003601
caenorhabditis_elegans		WBGENE00003608
caenorhabditis_elegans		WBGENE00003611
caenorhabditis_elegans		WBGENE00003614
caenorhabditis_elegans		WBGENE00003615
caenorhabditis_elegans		WBGENE00003617
caenorhabditis_elegans		WBGENE00003618
caenorhabditis_elegans		WBGENE00003620
caenorhabditis_elegans	nhr-23	WBGENE00003622
caenorhabditis_elegans		WBGENE00003624
caenorhabditis_elegans		WBGENE00003632
caenorhabditis_elegans		WBGENE00003634
caenorhabditis_elegans		WBGENE00003638
caenorhabditis_elegans		WBGENE00003640
caenorhabditis_elegans		WBGENE00003641
caenorhabditis_elegans		WBGENE00003642
caenorhabditis_elegans		WBGENE00003643
caenorhabditis_elegans		WBGENE00003644
caenorhabditis_elegans		WBGENE00003645
caenorhabditis_elegans		WBGENE00003646
caenorhabditis_elegans		WBGENE00003648
caenorhabditis_elegans		WBGENE00003649
caenorhabditis_elegans		WBGENE00003651
caenorhabditis_elegans		WBGENE00003653
caenorhabditis_elegans		WBGENE00003655
caenorhabditis_elegans		WBGENE00003658
caenorhabditis_elegans		WBGENE00003660
caenorhabditis_elegans		WBGENE00003662
caenorhabditis_elegans	nhr-73	WBGENE00003663
caenorhabditis_elegans	nhr-77	WBGENE00003667
caenorhabditis_elegans		WBGENE00003669
caenorhabditis_elegans	nhr-81	WBGENE00003671
caenorhabditis_elegans	nhr-82	WBGENE00003672
caenorhabditis_elegans		WBGENE00003676
caenorhabditis_elegans		WBGENE00003677
caenorhabditis_elegans		WBGENE00003680
caenorhabditis_elegans		WBGENE00003682
caenorhabditis_elegans		WBGENE00003684
caenorhabditis_elegans		WBGENE00003685
caenorhabditis_elegans		WBGENE00003686
caenorhabditis_elegans		WBGENE00003688
caenorhabditis_elegans		WBGENE00003689
caenorhabditis_elegans		WBGENE00003692
caenorhabditis_elegans		WBGENE00003693
caenorhabditis_elegans		WBGENE00003694
caenorhabditis_elegans		WBGENE00003696
caenorhabditis_elegans		WBGENE00003698
caenorhabditis_elegans		WBGENE00003699
caenorhabditis_elegans		WBGENE00003700
caenorhabditis_elegans		WBGENE00003702
caenorhabditis_elegans		WBGENE00003704
caenorhabditis_elegans		WBGENE00003705
caenorhabditis_elegans		WBGENE00003707
caenorhabditis_elegans		WBGENE00003708
caenorhabditis_elegans		WBGENE00003712
caenorhabditis_elegans		WBGENE00003713
caenorhabditis_elegans		WBGENE00003714
caenorhabditis_elegans		WBGENE00003715
caenorhabditis_elegans		WBGENE00003716
caenorhabditis_elegans		WBGENE00003717
caenorhabditis_elegans		WBGENE00003718
caenorhabditis_elegans		WBGENE00003720
caenorhabditis_elegans		WBGENE00003721
caenorhabditis_elegans		WBGENE00003722
caenorhabditis_elegans		WBGENE00003723
caenorhabditis_elegans		WBGENE00003724
caenorhabditis_elegans		WBGENE00003725
caenorhabditis_elegans		WBGENE00003728
caenorhabditis_elegans		WBGENE00004786
caenorhabditis_elegans		WBGENE00006471
caenorhabditis_elegans	unc-55	WBGENE00006790
caenorhabditis_elegans		WBGENE00007367
caenorhabditis_elegans		WBGENE00008056
caenorhabditis_elegans	nhr-165	WBGENE00008158
caenorhabditis_elegans		WBGENE00008208
caenorhabditis_elegans	nhr-169	WBGENE00008289
caenorhabditis_elegans		WBGENE00008309
caenorhabditis_elegans	nhr-174	WBGENE00008474
caenorhabditis_elegans		WBGENE00008619
caenorhabditis_elegans		WBGENE00008630
caenorhabditis_elegans		WBGENE00008778
caenorhabditis_elegans		WBGENE00008830
caenorhabditis_elegans		WBGENE00008884
caenorhabditis_elegans		WBGENE00008901
caenorhabditis_elegans	nhr-265	WBGENE00009608
caenorhabditis_elegans		WBGENE00010017
caenorhabditis_elegans		WBGENE00010180
caenorhabditis_elegans		WBGENE00010186
caenorhabditis_elegans		WBGENE00010215
caenorhabditis_elegans		WBGENE00010410
caenorhabditis_elegans		WBGENE00010600
caenorhabditis_elegans		WBGENE00010601
caenorhabditis_elegans		WBGENE00010602
caenorhabditis_elegans		WBGENE00010603
caenorhabditis_elegans		WBGENE00010604
caenorhabditis_elegans		WBGENE00011002
caenorhabditis_elegans		WBGENE00011150
caenorhabditis_elegans		WBGENE00011396
caenorhabditis_elegans		WBGENE00011520
caenorhabditis_elegans		WBGENE00011565
caenorhabditis_elegans		WBGENE00011566
caenorhabditis_elegans		WBGENE00011568
caenorhabditis_elegans	nhr-217	WBGENE00011651
caenorhabditis_elegans		WBGENE00011750
caenorhabditis_elegans		WBGENE00012050
caenorhabditis_elegans		WBGENE00012056
caenorhabditis_elegans		WBGENE00012446
caenorhabditis_elegans		WBGENE00012449
caenorhabditis_elegans		WBGENE00012596
caenorhabditis_elegans		WBGENE00012703
caenorhabditis_elegans		WBGENE00013067
caenorhabditis_elegans		WBGENE00013483
caenorhabditis_elegans	nhr-276	WBGENE00013512
caenorhabditis_elegans		WBGENE00013584
caenorhabditis_elegans		WBGENE00013940
caenorhabditis_elegans		WBGENE00014068
caenorhabditis_elegans	nhr-245	WBGENE00014189
caenorhabditis_elegans		WBGENE00014193
caenorhabditis_elegans		WBGENE00015497
caenorhabditis_elegans		WBGENE00015758
caenorhabditis_elegans		WBGENE00015897
caenorhabditis_elegans		WBGENE00015900
caenorhabditis_elegans		WBGENE00015901
caenorhabditis_elegans		WBGENE00015902
caenorhabditis_elegans		WBGENE00016091
caenorhabditis_elegans		WBGENE00016233
caenorhabditis_elegans		WBGENE00016364
caenorhabditis_elegans		WBGENE00016365
caenorhabditis_elegans		WBGENE00016366
caenorhabditis_elegans		WBGENE00016367
caenorhabditis_elegans		WBGENE00016368
caenorhabditis_elegans		WBGENE00016517
caenorhabditis_elegans		WBGENE00016772
caenorhabditis_elegans		WBGENE00016926
caenorhabditis_elegans		WBGENE00016927
caenorhabditis_elegans		WBGENE00017503
caenorhabditis_elegans		WBGENE00017512
caenorhabditis_elegans		WBGENE00017961
caenorhabditis_elegans		WBGENE00018189
caenorhabditis_elegans		WBGENE00018265
caenorhabditis_elegans		WBGENE00018266
caenorhabditis_elegans		WBGENE00018404
caenorhabditis_elegans		WBGENE00018412
caenorhabditis_elegans		WBGENE00018415
caenorhabditis_elegans		WBGENE00018539
caenorhabditis_elegans		WBGENE00018541
caenorhabditis_elegans		WBGENE00018542
caenorhabditis_elegans		WBGENE00018544
caenorhabditis_elegans		WBGENE00018545
caenorhabditis_elegans		WBGENE00018622
caenorhabditis_elegans		WBGENE00019115
caenorhabditis_elegans		WBGENE00019116
caenorhabditis_elegans		WBGENE00019741
caenorhabditis_elegans		WBGENE00019742
caenorhabditis_elegans		WBGENE00019743
caenorhabditis_elegans		WBGENE00020015
caenorhabditis_elegans		WBGENE00020062
caenorhabditis_elegans		WBGENE00020152
caenorhabditis_elegans		WBGENE00020153
caenorhabditis_elegans		WBGENE00020385
caenorhabditis_elegans		WBGENE00020460
caenorhabditis_elegans		WBGENE00020555
caenorhabditis_elegans		WBGENE00020750
caenorhabditis_elegans		WBGENE00020849
caenorhabditis_elegans		WBGENE00020850
caenorhabditis_elegans		WBGENE00020851
caenorhabditis_elegans		WBGENE00020852
caenorhabditis_elegans		WBGENE00021163
caenorhabditis_elegans		WBGENE00021522
caenorhabditis_elegans		WBGENE00021610
caenorhabditis_elegans		WBGENE00021611
caenorhabditis_elegans		WBGENE00021617
caenorhabditis_elegans		WBGENE00022097
caenorhabditis_elegans		WBGENE00022637
caenorhabditis_elegans		WBGENE00022639
caenorhabditis_elegans		WBGENE00022640
caenorhabditis_elegans		WBGENE00022726
caenorhabditis_elegans		WBGENE00022756
caenorhabditis_elegans		WBGENE00022805
caenorhabditis_elegans		WBGENE00044353
caenorhabditis_elegans		WBGENE00044699
caenorhabditis_elegans		WBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), NR1I2 (ENSG00000144852), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Protein

Protein identifiers

Nuclear receptor subfamily 1 group D member 1 — P20393 (reviewed: P20393)

Alternative names: Rev-erbA-alpha, V-erbA-related protein 1

All UniProt accessions (2): P20393, F1D8S3

UniProt curated annotations — full annotation on UniProt →

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 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 G6PC1 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. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14. Represses the transcription of CES2. Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner. Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity. Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response. Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system. Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle.

Subunit / interactions. Binds DNA as a monomer or a homodimer. Interacts with C1D, NR2E3 and SP1. Interacts with OPHN1 (via C-terminus). Interacts with ZNHIT1. Interacts with PER2; the interaction associates PER2 to BMAL1 promoter region. Interacts with CRY1. Interacts with CCAR2. Interacts with SIAH2. Interacts with CDK1. Interacts with FBXW7. Interacts with HUWE1. Interacts with NR0B2. Interacts with NFIL3. Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1.

Subcellular location. Nucleus. Cytoplasm. Cell projection. Dendrite. Dendritic spine.

Tissue specificity. Widely expressed. Expressed at high levels in the liver, adipose tissue, skeletal muscle and brain. Also expressed in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and macrophages. Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral tissues. Expression increases during the differentiation of pre-adipocytes into mature adipocytes. Expressed at high levels in some squamous carcinoma cell lines.

Post-translational modifications. Ubiquitinated, leading to its proteasomal degradation. Ubiquitinated by SIAH2; leading to its proteasomal degradation. Ubiquitinated by the SCF(FBXW7) complex when phosphorylated by CDK1 leading to its proteasomal degradation. Rapidly ubiquitinated in response to inflammatory triggers and sumoylation is a prerequisite to its ubiquitination. Sumoylated by UBE2I, desumoylated by SENP1, and sumoylation is a prerequisite to its ubiquitination. Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic localization. Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Similarity. Belongs to the nuclear hormone receptor family. NR1 subfamily.

RefSeq proteins (1): NP_068370* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050234	Nuclear_hormone_rcpt_NR1	Family

Pfam: PF00104, PF00105

UniProt features (54 total): helix 13, compositionally biased region 7, modified residue 7, strand 7, region of interest 6, turn 5, binding site 2, sequence conflict 2, zinc finger region 2, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1A6Y	X-RAY DIFFRACTION	2.3
1GA5	X-RAY DIFFRACTION	2.4
8D8I	X-RAY DIFFRACTION	2.5
3N00	X-RAY DIFFRACTION	2.6
1HLZ	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20393-F1	63.87	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 418; 602

Post-translational modifications (7): 55, 59, 191, 192, 274, 400, 591

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-9707616	Heme signaling
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9931510	Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression
R-HSA-9931512	Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters
R-HSA-9931521	The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex

MSigDB gene sets: 453 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, ENK_UV_RESPONSE_KERATINOCYTE_UP

GO Biological Process (36): negative regulation of transcription by RNA polymerase II (GO:0000122), intracellular glucose homeostasis (GO:0001678), glycogen biosynthetic process (GO:0005978), hormone-mediated signaling pathway (GO:0009755), proteasomal protein catabolic process (GO:0010498), regulation of lipid metabolic process (GO:0019216), cell differentiation (GO:0030154), intracellular receptor signaling pathway (GO:0030522), protein destabilization (GO:0031648), circadian regulation of gene expression (GO:0032922), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), cholesterol homeostasis (GO:0042632), regulation of circadian sleep/wake cycle (GO:0042749), regulation of circadian rhythm (GO:0042752), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), response to leptin (GO:0044321), regulation of fat cell differentiation (GO:0045598), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of inflammatory response (GO:0050728), circadian temperature homeostasis (GO:0060086), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), regulation of type B pancreatic cell proliferation (GO:0061469), negative regulation of astrocyte activation (GO:0061889), positive regulation of bile acid biosynthetic process (GO:0070859), cellular response to lipopolysaccharide (GO:0071222), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356), negative regulation of cold-induced thermogenesis (GO:0120163), negative regulation of neuroinflammatory response (GO:0150079), negative regulation of microglial cell activation (GO:1903979), regulation of DNA-templated transcription (GO:0006355), circadian rhythm (GO:0007623), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), rhythmic process (GO:0048511)

GO Molecular Function (17): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription corepressor binding (GO:0001222), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), heme binding (GO:0020037), E-box binding (GO:0070888), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604), dendrite (GO:0030425), dendritic spine (GO:0043197), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Circadian clock	5
Regulation of lipid metabolism by PPARalpha	1
Mitochondrial biogenesis	1
Generic Transcription Pathway	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
circadian rhythm	2
DNA-templated transcription	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
negative regulation of DNA-templated transcription	1
glucose homeostasis	1
intracellular chemical homeostasis	1
glycogen metabolic process	1
glucan biosynthetic process	1
signal transduction	1
cellular response to hormone stimulus	1
protein catabolic process	1
lipid metabolic process	1
regulation of primary metabolic process	1
cellular developmental process	1
intracellular signal transduction	1
regulation of protein stability	1
regulation of gene expression	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
sterol homeostasis	1
circadian sleep/wake cycle	1
regulation of circadian rhythm	1
regulation of behavior	1
regulation of biological process	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
response to hormone	1
fat cell differentiation	1
regulation of cell differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

1448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR1D1	PER2	O15055	998
NR1D1	NCOR1	O75376	990
NR1D1	BMAL1	O00327	979
NR1D1	CRY1	Q16526	977
NR1D1	PER3	P56645	972
NR1D1	NPAS2	Q99743	972
NR1D1	NFIL3	Q16649	964
NR1D1	CLOCK	O15516	951
NR1D1	CRY2	Q49AN0	947
NR1D1	BHLHE41	Q9C0J9	933
NR1D1	BHLHE40	O14503	927
NR1D1	HDAC3	O15379	826
NR1D1	CSNK1E	P49674	825
NR1D1	TIMELESS	Q9UNS1	800
NR1D1	ONECUT1	Q9UBC0	797

IntAct

39 interactions, top by confidence:

A	B	Type	Score
NR1D1	NCOR1	psi-mi:“MI:0407”(direct interaction)	0.600
NR1D1	NCOR1	psi-mi:“MI:0915”(physical association)	0.600
INPP1	NR1D1	psi-mi:“MI:0915”(physical association)	0.560
NR1D1	TDO2	psi-mi:“MI:0915”(physical association)	0.560
NR1D1	SPG21	psi-mi:“MI:0915”(physical association)	0.560
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
NR1D1	APOA4	psi-mi:“MI:0403”(colocalization)	0.520
NR1D1	APOA4	psi-mi:“MI:2364”(proximity)	0.520
NR1D1	APOA4	psi-mi:“MI:0915”(physical association)	0.520
NR1D1	HUWE1	psi-mi:“MI:0915”(physical association)	0.500
Per2	NR1D1	psi-mi:“MI:0915”(physical association)	0.500
Per2	NR1D1	psi-mi:“MI:0914”(association)	0.500
NR1D1		psi-mi:“MI:0407”(direct interaction)	0.440
NR1D1	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
NR1D1		psi-mi:“MI:0915”(physical association)	0.400
INPP1	NR1D1	psi-mi:“MI:0915”(physical association)	0.370
IL17F	NR1D1	psi-mi:“MI:0915”(physical association)	0.370
NR1D1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
NR1D1	MYCBP2	psi-mi:“MI:0914”(association)	0.350
NR1D1	HDAC3	psi-mi:“MI:0914”(association)	0.350
NR1D2	NR1D1	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
CIAO2A		psi-mi:“MI:0914”(association)	0.350
SPSB4	BTAF1	psi-mi:“MI:0914”(association)	0.350
SPANXN3	OGA	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): NR1D1 (Affinity Capture-MS), NR1D1 (FRET), NR2E3 (FRET), NR1D1 (Two-hybrid), NR1D1 (Affinity Capture-Western), YAP1 (Affinity Capture-Western), NR1D1 (Affinity Capture-Western), NR1D1 (Co-localization), NR1D1 (Two-hybrid), TDO2 (Two-hybrid), SPSB4 (Affinity Capture-Western), NR1D1 (Affinity Capture-Western), NR1D1 (Phenotypic Enhancement), NR1D1 (Two-hybrid), NR1D1 (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z4, A4IIG7, B3SV56, O00482, O42101, P06211, P06212, P19785, P19793, P20393, P28700, P28701, P28705, P35398, P43354, P45448, P48443, P49867, P49868, P49884, P51128, P51129, P51179, P57783, P81559, Q04913, Q06219, Q07917, Q08882, Q08E02, Q08E53, Q0GFF6, Q0VC20, Q15406, Q29040, Q3UV55, Q505F1, Q5BJR8, Q5R5Y4, Q5REL6

Diamond homologs: A4IIG7, B3SV56, F1QJF4, F1QLY4, G5EDJ0, O01639, O08580, O09017, O09018, O45436, O76202, O77245, O95718, P10588, P10589, P11474, P11475, P12813, P13055, P16375, P16376, P17671, P17672, P18515, P20153, P20393, P22736, P22829, P24468, P28702, P33242, P35398, P41235, P41830, P43135, P43136, P43354, P45446, P45447, P49700

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
NR1D1	up-regulates	NR2E3
NR2E3	up-regulates	NR1D1	binding
GSK3B	up-regulates	NR1D1	phosphorylation
C1D	“up-regulates activity”	NR1D1	binding
NR1D1	“down-regulates quantity by repression”	ARNTL	“transcriptional regulation”
RORA	“down-regulates activity”	NR1D1	binding
NR1D1	“down-regulates quantity by repression”	NPAS2	“transcriptional regulation”
PPARGC1A	“up-regulates quantity by expression”	NR1D1	“transcriptional regulation”
NR1D1	“up-regulates activity”	OPHN1	binding
PPARG	“up-regulates quantity by expression”	NR1D1	“transcriptional regulation”
NR1D1	up-regulates	Adipogenesis

Disease & clinical

Clinical variants and AI predictions

ClinVar

87 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	70
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1299533	NM_003250.6(THRA):c.1416dup (p.Ser473fs)	Pathogenic

SpliceAI

872 predictions. Top by Δscore:

Variant	Effect	Δscore
17:40093278:GCGGT:G	acceptor_gain	1.0000
17:40093279:CGGT:C	acceptor_gain	1.0000
17:40093279:CGGTC:C	acceptor_gain	1.0000
17:40093280:GGT:G	acceptor_gain	1.0000
17:40093281:GT:G	acceptor_gain	1.0000
17:40093282:TCTG:T	acceptor_loss	1.0000
17:40093283:C:A	acceptor_loss	1.0000
17:40093283:C:CC	acceptor_gain	1.0000
17:40093284:T:G	acceptor_loss	1.0000
17:40093908:CTA:C	donor_loss	1.0000
17:40093909:TA:T	donor_loss	1.0000
17:40093910:A:AC	donor_gain	1.0000
17:40093911:C:CA	donor_loss	1.0000
17:40093911:C:CC	donor_gain	1.0000
17:40093911:CCTG:C	donor_gain	1.0000
17:40093927:C:CT	donor_gain	1.0000
17:40094118:AGCAC:A	acceptor_gain	1.0000
17:40094119:GCAC:G	acceptor_gain	1.0000
17:40094120:CAC:C	acceptor_gain	1.0000
17:40094120:CACC:C	acceptor_gain	1.0000
17:40094121:AC:A	acceptor_gain	1.0000
17:40094122:CC:C	acceptor_gain	1.0000
17:40094123:C:CC	acceptor_gain	1.0000
17:40094931:TCA:T	donor_loss	1.0000
17:40094932:CA:C	donor_loss	1.0000
17:40094933:A:AC	donor_gain	1.0000
17:40094934:C:CC	donor_gain	1.0000
17:40094934:C:CT	donor_loss	1.0000
17:40094934:CCT:C	donor_gain	1.0000
17:40095116:CATGC:C	acceptor_gain	1.0000

AlphaMissense

4024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:40093923:A:G	L545P	1.000
17:40093923:A:T	L545H	1.000
17:40093932:G:T	A542E	1.000
17:40093933:C:G	A542P	1.000
17:40093938:A:G	F540S	1.000
17:40093977:A:G	L527P	1.000
17:40094066:G:C	F497L	1.000
17:40094066:G:T	F497L	1.000
17:40094067:A:G	F497S	1.000
17:40094068:A:G	F497L	1.000
17:40094094:A:G	F488S	1.000
17:40094118:A:G	L480P	1.000
17:40094945:C:T	G475D	1.000
17:40094950:C:A	K473N	1.000
17:40094950:C:G	K473N	1.000
17:40094954:A:G	L472P	1.000
17:40094954:A:T	L472H	1.000
17:40094957:A:G	L471P	1.000
17:40094981:A:G	L463P	1.000
17:40094989:G:C	F460L	1.000
17:40094989:G:T	F460L	1.000
17:40094990:A:G	F460S	1.000
17:40094991:A:G	F460L	1.000
17:40095008:G:T	A454D	1.000
17:40095009:C:G	A454P	1.000
17:40095010:A:C	F453L	1.000
17:40095010:A:T	F453L	1.000
17:40095011:A:C	F453C	1.000
17:40095011:A:G	F453S	1.000
17:40095012:A:G	F453L	1.000

dbSNP variants (sampled 300 via entrez): RS1000270585 (17:40096936 T>C,G), RS1000446914 (17:40098124 T>C), RS1000548258 (17:40097856 G>C), RS1000737935 (17:40093882 T>C), RS1000928117 (17:40094401 A>G), RS1001002680 (17:40099964 G>A), RS1001124600 (17:40095675 G>T), RS1001339408 (17:40093819 C>A,G,T), RS1001811538 (17:40101425 G>C), RS1002556928 (17:40100485 T>C,G), RS1002631120 (17:40099232 G>A), RS1003233486 (17:40097970 C>A,T), RS1004128148 (17:40096929 G>A,C,T), RS1004337780 (17:40099146 G>A,T), RS1004519921 (17:40100174 G>T)

Disease associations

OMIM: gene MIM:602408 | disease phenotypes: MIM:614450

GenCC curated gene-disease

Mondo (1): congenital nongoitrous hypothyroidism 6 (MONDO:0013757)

Orphanet (1): OBSOLETE: Peripheral resistance to thyroid hormones (Orphanet:97927)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001137_10	White blood cell count	9.000000e-35
GCST001137_8	White blood cell count	2.000000e-31
GCST008916_21	Asthma	2.000000e-62
GCST008916_85	Asthma	2.000000e-12
GCST009597_274	Multiple sclerosis	9.000000e-14
GCST90002392_15	Mean corpuscular volume	3.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1961783 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2071427	Efficacy	3	lithium	Bipolar Disorder
rs2314339	Efficacy	3	lithium	Bipolar Disorder

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs939347	NR1D1		0.00	0
rs2071427	NR1D1, THRA	3	0.25	1	lithium
rs2071570	NR1D1		0.00	0
rs2269457	NR1D1, THRA		0.00	0
rs2314339	NR1D1, THRA	3	2.50	1	lithium
rs4794826	NR1D1, THRA		0.00	0
rs12941497	NR1D1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 1D. Rev-Erb receptors

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
SR8278	Antagonist	6.3	pEC50
SR9009	Agonist	6.17	pIC50
SR9011	Agonist	6.1	pIC50
GSK4112	Agonist	5.64	pIC50

ChEMBL bioactivities

134 potent at pChembl≥5 of 135 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	EC50	6	nM	CHEMBL5434615
8.15	EC50	7	nM	CHEMBL5408866
8.00	EC50	10	nM	CHEMBL5419854
7.70	EC50	20	nM	CHEMBL5417493
7.70	EC50	20	nM	CHEMBL5424373
7.60	EC50	25	nM	CHEMBL5407367
7.40	EC50	40	nM	CHEMBL5404180
7.30	EC50	50	nM	CHEMBL2381196
7.30	EC50	50	nM	CHEMBL4761268
7.30	EC50	50	nM	CHEMBL5436011
7.27	EC50	54	nM	CHEMBL5424215
7.20	EC50	63	nM	CHEMBL2381198
7.17	EC50	68	nM	CHEMBL4781178
7.16	EC50	70	nM	CHEMBL5439268
7.16	EC50	70	nM	CHEMBL5412941
7.11	EC50	77	nM	CHEMBL2030074
7.10	EC50	80	nM	CHEMBL5434147
7.01	EC50	97	nM	CHEMBL2030073
7.00	EC50	100	nM	CHEMBL2381197
6.96	EC50	110	nM	CHEMBL5432192
6.92	EC50	120	nM	CHEMBL2030072
6.92	EC50	120	nM	CHEMBL2030077
6.92	EC50	120	nM	CHEMBL5435001
6.91	EC50	123	nM	CHEMBL5438917
6.85	EC50	140	nM	CHEMBL2030075
6.82	EC50	150	nM	CHEMBL4763333
6.80	EC50	160	nM	CHEMBL2381202
6.80	EC50	160	nM	CHEMBL2381201
6.80	EC50	160	nM	CHEMBL2381200
6.80	EC50	160	nM	CHEMBL2381199
6.80	EC50	160	nM	CHEMBL5429567
6.70	EC50	200	nM	CHEMBL2381193
6.70	EC50	200	nM	CHEMBL2381214
6.70	EC50	200	nM	CHEMBL2381208
6.70	EC50	200	nM	CHEMBL2381205
6.70	EC50	200	nM	CHEMBL2381204
6.70	EC50	200	nM	CHEMBL2381203
6.60	EC50	250	nM	CHEMBL2381209
6.48	EC50	330	nM	CHEMBL2030081
6.48	EC50	330	nM	CHEMBL5435835
6.43	EC50	370	nM	CHEMBL5396141
6.41	EC50	390	nM	CHEMBL5432560
6.40	EC50	400	nM	GSK-4112
6.40	EC50	400	nM	CHEMBL2059696
6.40	EC50	400	nM	CHEMBL2381210
6.40	EC50	400	nM	CHEMBL2381207
6.40	EC50	400	nM	CHEMBL2381206
6.35	EC50	450	nM	CHEMBL2059700
6.33	EC50	470	nM	CHEMBL4754504
6.33	IC50	470	nM	CHEMBL4754504

PubChem BioAssay actives

133 with measured affinity, of 379 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[[1-(2-methylpropyl)-6-[2-(trifluoromethyl)phenyl]indol-3-yl]methyl]cyclopropanesulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0060	uM
N-[1-[1-(2-methylpropyl)-6-[2-(trifluoromethyl)phenyl]indol-3-yl]ethyl]cyclopropanesulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0070	uM
1-[2-(dimethylsulfamoylamino)ethyl]-3-(2-methylpropyl)-5-pyridin-4-ylindole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0100	uM
3-[2-(dimethylsulfamoylamino)ethyl]-1-(2-methylpropyl)-6-pyridin-4-ylindole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0200	uM
1-[2-(dimethylsulfamoylamino)ethyl]-3-(2-methylpropyl)-5-pyridin-4-ylpyrrolo[2,3-b]pyridine	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0200	uM
N-[2-[1-(2-methylpropyl)-6-pyridin-4-ylindol-3-yl]ethyl]cyclopropanesulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0250	uM
N-[2-[1-(2-methylpropyl)-6-[2-(trifluoromethyl)phenyl]indol-3-yl]ethyl]cyclopropanesulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0400	uM
N-[(3-chloro-5-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.0500	uM
6-(2-chlorophenyl)-3-[2-(dimethylsulfamoylamino)ethyl]-1-(2-methylpropyl)indole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0500	uM
N-[(4-chloro-2-methylphenyl)methyl]-1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.0500	uM
N-[2-[1-(2-methylpropyl)-6-pyridin-4-ylindol-3-yl]ethyl]propane-2-sulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0540	uM
1-(4-chlorophenyl)-N-[(2-fluorophenyl)methyl]-N-[(5-nitrothiophen-2-yl)methyl]methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.0630	uM
[(3S)-6-fluoro-3-[[4-[(2-methylpropan-2-yl)oxy]phenoxy]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-naphthalen-1-ylmethanone	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.0680	uM
3-[2-(dimethylsulfamoylamino)ethyl]-1-(2-methylpropyl)-6-phenylindole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0700	uM
3-[2-(dimethylsulfamoylamino)ethyl]-1-(2-methylpropyl)-6-[2-(trifluoromethyl)phenyl]indole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0700	uM
naphthalen-1-yl-[3-[(4-propoxyphenoxy)methyl]-3,4-dihydro-1H-isoquinolin-2-yl]methanone	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.0770	uM
6-cyclopropyl-3-[2-(dimethylsulfamoylamino)ethyl]-1-(2-methylpropyl)indole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.0800	uM
[3-[(4-ethoxyphenoxy)methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-naphthalen-1-ylmethanone	661921: Agonist activity at Rev-erbalpha assessed as repression of transcription by luciferase-reporter gene assay	ec50	0.0970	uM
N-[(4-chlorophenyl)methyl]-N-[(5-nitrothiophen-2-yl)methyl]-1-phenylmethanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.1000	uM
N-[2,2,2-trifluoro-1-[1-(2-methylpropyl)-6-[2-(trifluoromethyl)phenyl]indol-3-yl]ethyl]cyclopropanesulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.1100	uM
3-[2-(dimethylsulfamoylamino)ethyl]-6-methyl-1-(2-methylpropyl)indole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.1200	uM
[3-[(4-methoxyphenoxy)methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-naphthalen-1-ylmethanone	661921: Agonist activity at Rev-erbalpha assessed as repression of transcription by luciferase-reporter gene assay	ec50	0.1200	uM
naphthalen-1-yl-[3-[[4-(1,2,4-triazol-1-yl)phenoxy]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]methanone	661921: Agonist activity at Rev-erbalpha assessed as repression of transcription by luciferase-reporter gene assay	ec50	0.1200	uM
N-[2-[1-(2-methylpropyl)-6-pyridin-4-ylindol-3-yl]ethyl]pyrrolidine-1-sulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.1230	uM
[3-[[4-[(2-methylpropan-2-yl)oxy]phenoxy]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-naphthalen-1-ylmethanone	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.1400	uM
2-[4-[(4-chlorophenyl)methyl-methylamino]phenyl]-5-(2-methoxyethylamino)-1,3-oxazole-4-carbonitrile	1722010: Inverse agonist activity at Rev-Erb alpha LBD (unknown origin) by FRET assay	ec50	0.1500	uM
3-[2-(dimethylsulfamoylamino)ethyl]-1-(2-methylpropyl)-6-pyridin-3-ylindole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.1600	uM
N-[(4-chlorophenyl)methyl]-3-methyl-N-[(5-nitrothiophen-2-yl)methyl]butan-1-amine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.1600	uM
1-(4-chlorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]-N-(pyridin-3-ylmethyl)methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.1600	uM
1-(4-methylphenyl)-N-[(5-nitrothiophen-2-yl)methyl]-N-(pyridin-3-ylmethyl)methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.1600	uM
1-(4-fluorophenyl)-N-[(5-nitrothiophen-2-yl)methyl]-N-(pyridin-3-ylmethyl)methanamine	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.1600	uM
N-[(2-methylphenyl)methyl]-N-[(5-nitrothiophen-2-yl)methyl]-1-pyridin-3-ylmethanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.2000	uM
N-[(3-methylphenyl)methyl]-N-[(5-nitrothiophen-2-yl)methyl]-1-pyridin-3-ylmethanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.2000	uM
1-(4-methoxyphenyl)-N-[(5-nitrothiophen-2-yl)methyl]-N-(pyridin-3-ylmethyl)methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.2000	uM
5-[[(4-chlorophenyl)methyl-(pyridin-3-ylmethyl)amino]methyl]thiophene-2-carbonitrile	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.2000	uM
5-[[(4-fluorophenyl)methyl-(pyridin-3-ylmethyl)amino]methyl]thiophene-2-carbonitrile	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.2000	uM
5-[[(3,4-difluorophenyl)methyl-(pyridin-3-ylmethyl)amino]methyl]thiophene-2-carbonitrile	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.2000	uM
N-[(4-bromo-5-methylthiophen-2-yl)methyl]-1-(4-chlorophenyl)-N-(pyridin-3-ylmethyl)methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.2500	uM
3-[2-(dimethylsulfamoylamino)ethyl]-6-(2-methoxyphenyl)-1-(2-methylpropyl)indole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.3300	uM
[3-[(3,4-dimethoxyphenoxy)methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-naphthalen-1-ylmethanone	661921: Agonist activity at Rev-erbalpha assessed as repression of transcription by luciferase-reporter gene assay	ec50	0.3300	uM
6-(3-cyanophenyl)-3-[2-(dimethylsulfamoylamino)ethyl]-1-(2-methylpropyl)indole	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.3700	uM
N-[2-[1-(2-methylpropyl)-6-[2-(trifluoromethyl)phenyl]indol-3-yl]propan-2-yl]cyclopropanesulfonamide	2020974: Agonist activity at his6-tagged human REV-ERBalpha LBD (281 to 614 residues) expressed in Escherichia coli assessed as increase in SMRT corepressor peptide requirement by TR-FRET assay incubated for 2 hrs by TR-FRET assay	ec50	0.3900	uM
tert-butyl 2-[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]acetate	661919: Agonist activity at Rev-erbalpha assessed as NCoR recruitment by FRET assay	ec50	0.4000	uM
3-[[(4-chlorophenyl)methyl-[(5-nitrothiophen-2-yl)methyl]amino]methyl]-N-(4-nitrophenyl)pyrrolidine-1-carboxamide	671968: Agonist activity at Rev-Erbalpha expressed in HEK293 cells coexpressing BamII promoter assessed as repression of transcription after 24 hrs by dual-Glo luciferase assay	ec50	0.4000	uM
1-(3-methoxyphenyl)-N-[(5-nitrothiophen-2-yl)methyl]-N-(pyridin-3-ylmethyl)methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.4000	uM
N-[(5-nitrothiophen-2-yl)methyl]-N-(pyridin-3-ylmethyl)-1-[3-(trifluoromethyl)phenyl]methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.4000	uM
N-(1-benzothiophen-2-ylmethyl)-1-(4-chlorophenyl)-N-(pyridin-3-ylmethyl)methanamine	747991: Agonist activity at biotinylated REV-ERBalpha (unknown origin) assessed as increase in biotinylated NCOR peptide recruitment after 1 hr by FRET assay	ec50	0.4000	uM
N-[(4-chlorophenyl)methyl]-1-(1-naphthalen-1-ylsulfonylpyrrolidin-3-yl)-N-[(5-nitrothiophen-2-yl)methyl]methanamine	671968: Agonist activity at Rev-Erbalpha expressed in HEK293 cells coexpressing BamII promoter assessed as repression of transcription after 24 hrs by dual-Glo luciferase assay	ec50	0.4500	uM
ethyl 2-(5-methylsulfanylthiophene-2-carbonyl)-3,4-dihydro-1H-isoquinoline-3-carboxylate	1722008: Antagonist activity at Rev-Erb alpha (unknown origin) by BMAL1-luciferase reporter assay	ec50	0.4700	uM
7-[2-(2-chlorothiophen-3-yl)-5-(trifluoromethyl)phenoxy]-5-methylthieno[2,3-d]pyridazin-4-one	1722006: Agonist activity at Rev-Erb alpha (unknown origin) by FRET assay	ec50	0.5200	uM

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	3
(+)-JQ1 compound	decreases expression	2
Silicon Dioxide	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
Glupearl 19S	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
bisphenol A	affects expression	1
deoxynivalenol	increases expression	1
geraniol	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
titanium dioxide	decreases methylation	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
polyhexamethyleneguanidine	affects expression	1
2-(4-(2-carboxyethyl)phenethylamino)-5’-N-ethylcarboxamidoadenosine	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
cylindrospermopsin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
ormosil	affects binding, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
KL001	decreases reaction, increases expression	1
Leflunomide	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1

ChEMBL screening assays

32 unique, capped per target: 22 binding, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1961798	Binding	Increased REV-ERB-alpha LBD dependent repressor activity in HEK293 cell reporter assay	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature
CHEMBL1961800	Functional	REV-ERB-alpha mediated transcriptional suppression at Bmal1 promoter in HEK293 cell reporter assay	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4S4	SEES3-1V human NR1D1, clone1	Embryonic stem cell	Male
CVCL_A4S5	SEES3-1V human NR1D1, clone2	Embryonic stem cell	Male
CVCL_A4S6	SEES3-1V human NR1D1, clone3	Embryonic stem cell	Male
CVCL_D1XU	Abcam A-549 NR1D1 KO	Cancer cell line	Male
CVCL_D2C3	Abcam HCT 116 NR1D1 KO	Cancer cell line	Male
CVCL_D7W2	Ubigene A-549 NR1D1 KO	Cancer cell line	Male
CVCL_D8RN	Ubigene HCT 116 NR1D1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.