NR2E1

Summary

NR2E1 (nuclear receptor subfamily 2 group E member 1, HGNC:7973) is a protein-coding gene on chromosome 6q21, encoding Nuclear receptor subfamily 2 group E member 1 (Q9Y466). Orphan receptor that binds DNA as a monomer to hormone response elements (HRE) containing an extended core motif half-site sequence 5’-AAGGTCA-3’ in which the 5’ flanking nucleotides participate in determining receptor specificity.

The protein encoded by this gene is an orphan receptor involved in retinal development. The encoded protein also regulates adult neural stem cell proliferation and may be involved in control of aggressive behavior. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7101 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly (Limited, GenCC)
• Clinical variants (ClinVar): 42 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Transcription factor: yes — 19 downstream targets (CollecTRI)
• MANE Select transcript: NM_003269

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7973
Approved symbol	NR2E1
Name	nuclear receptor subfamily 2 group E member 1
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	TLL, XTLL
Ensembl gene	ENSG00000112333
Ensembl biotype	protein_coding
OMIM	603849
Entrez	7101

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000368983, ENST00000368986, ENST00000426403, ENST00000484978, ENST00000852831

RefSeq mRNA: 2 — MANE Select: NM_003269 NM_001286102, NM_003269

CCDS: CCDS5063, CCDS69165

Canonical transcript exons

ENST00000368986 — 9 exons

Exon	Start	End
ENSE00001448526	108166022	108166790
ENSE00001943523	108187301	108188805
ENSE00002019101	108180323	108180419
ENSE00002021271	108181546	108181651
ENSE00002029320	108178095	108178241
ENSE00002088004	108180807	108180956
ENSE00003523831	108174836	108174923
ENSE00003534797	108171458	108171603
ENSE00003622419	108176503	108176738

Expression profiles

Bgee: expression breadth broad, 84 present calls, max score 98.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1999 / max 63.1618, expressed in 137 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69179	0.5906	124
69177	0.4953	119
69178	0.1140	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.25	gold quality
secondary oocyte	CL:0000655	98.11	gold quality
oocyte	CL:0000023	95.99	gold quality
ganglionic eminence	UBERON:0004023	94.08	gold quality
pigmented layer of retina	UBERON:0001782	90.92	gold quality
caudate nucleus	UBERON:0001873	86.99	gold quality
medial globus pallidus	UBERON:0002477	86.39	gold quality
amygdala	UBERON:0001876	86.10	gold quality
putamen	UBERON:0001874	85.14	gold quality
nucleus accumbens	UBERON:0001882	85.13	gold quality
temporal lobe	UBERON:0001871	84.12	gold quality
entorhinal cortex	UBERON:0002728	83.49	gold quality
globus pallidus	UBERON:0001875	83.11	gold quality
cingulate cortex	UBERON:0003027	82.28	gold quality
anterior cingulate cortex	UBERON:0009835	82.14	gold quality
postcentral gyrus	UBERON:0002581	81.83	gold quality
telencephalon	UBERON:0001893	81.17	gold quality
right frontal lobe	UBERON:0002810	81.17	gold quality
buccal mucosa cell	CL:0002336	80.67	gold quality
superior frontal gyrus	UBERON:0002661	80.51	gold quality
choroid plexus epithelium	UBERON:0003911	80.47	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.33	gold quality
Ammon’s horn	UBERON:0001954	80.22	gold quality
cerebral cortex	UBERON:0000956	79.55	gold quality
parietal lobe	UBERON:0001872	79.44	gold quality
CA1 field of hippocampus	UBERON:0003881	79.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.79	gold quality
neocortex	UBERON:0001950	78.61	gold quality
endothelial cell	CL:0000115	78.22	gold quality
frontal cortex	UBERON:0001870	77.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	15.61
E-ANND-3	yes	3.93

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

19 targets.

Target	Regulation
ATCAY
CDKN1A	Activation
DCX
EGF
FABP7	Activation
GADD45G	Repression
GFAP	Activation
KDM1A
NR2E1	Repression
PAX2	Repression
PLCE1	Repression
PTEN	Repression
RAF1
RASA1
SHH
SIRT1
TGFA
VEGFA	Repression
WNT2

JASPAR motifs

Motif	Name	Family
MA0676.1	Nr2e1	RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:10706625

Upstream regulators (CollecTRI, top): NR2E1, SOX2

miRNA regulators (miRDB)

115 targeting NR2E1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-4698	99.84	71.41	4303

Literature-anchored findings (GeneRIF, showing 37)

• compared sequence from human, mouse, and the puffer fish Fugu rubripes (PMID:12079282)
• Transgenic human NR2E1 was sufficient to fix structural brain & eye abnormalities & hyperaggressiveness in mice deleted for mouse Nr2e1. NR2E1 protein & regulatory sequences are comparable between these species. (PMID:16000615)
• Strong purifying selection, low genetic diversity, 21 novel polymorphisms and five common haplotypes at were detected at NR2E1; protein-coding changes do not contribute to cortical and behavioral abnormalities, but regulatory mutations may play a role. (PMID:17054721)
• we cannot exclude the possibility that deletions at NR2E1 may underlie MMEP, given that sequencing is unable to distinguish between homozygosity across loci versus large deletions (PMID:17655765)
• TLX recruits histone deacetylases to repress transcription of p21(CIP1/WAF1) and pten and regulate neural stem cell proliferation (PMID:17873065)
• Genetic variation at NR2E1 may be associated with susceptibility to brain-behavior disorders. (PMID:18205168)
• LSD1 is a histone demethylase that is the prime corepressor for TLX (PMID:18391013)
• TLX is an inducer of SIRT1 and may contribute to neurogenesis both as a transactivator and as a repressor. (PMID:19555662)
• nuclear receptor tailless transcripts are overexpressed in human primary glioblastomas in which Tlx expression is restricted to a subpopulation of nestin-positive perivascular tumor cells (PMID:20360385)
• Increased TLX expression was observed in a number of glioma cells and glioma stem cells, and correlated with poor survival of patients with gliomas. (PMID:20814749)
• Nuclear orphan receptor TLX induces Oct-3/4 for the survival and maintenance of adult hippocampal progenitors upon hypoxia. (PMID:21135096)
• Transgenic mice lacking microRNAs miR-9-2 and miR-9-3 exhibit multiple defects of telencephalic structures which may be brought about by dysregulation of Foxg1, Nr2e1, Gsh2, and Meis2 expression. (PMID:21368052)
• Transgenic TLX acts as an essential regulator that ensures the proliferative ability of postnatal neural stem cells by controlling their activation through genetic interaction with p53 and other signaling pathways. (PMID:21957244)
• Cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null mice phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1. (PMID:22290436)
• BCL11A is a novel TLX coregulator that might be involved in TLX-dependent gene regulation in the brain. (PMID:22675500)
• Enriched expression of TLX in higher-grade human gliomas is observed. (PMID:23028043)
• No mutations in the NR2E1 gene were found in aniridia patients. (PMID:23213277)
• TLX is involved in interleukin (IL)-1beta-induced changes in adult hippocampal neurogenesis. (PMID:23510989)
• Interaction of NSD1 with the NR2E/F subfamily including COUP-TFI, COUP-TFII, EAR2 and TLX requires an F/YSXXLXXL/Y motif. Interactions of NSD1 with liganded NRs require an overlapping LXXLL motif. (PMID:23975195)
• TLX/NR2E1 and related NRs such as PNR and COUPTFs can selectively associate with the developmental corepressor BCL11A via a conserved motif F/YSXXLXXL/Y within the RID1 and RID2 domains. The interaction with BCL11A facilitates TLX-mediated repression of the RARb2 gene. (PMID:23975195)
• These results suggest that let-7b, by forming a negative feedback loop with TLX, provides a novel model to regulate the proliferation and differentiation of retinal progenitors in vitro (PMID:25327364)
• NR2E1 regulates CBX7 and restrains senescence in neural stem cells. (PMID:25328137)
• The effect of TLX on the proliferative, invasive and migratory properties of IMR-32 cells attributed to the recruitment of TLX to both MMP-2 and Oct-4 gene promoters, which resulted in the respective gene activation. (PMID:25356871)
• TLX functions as a potent suppressor of oncogene-induced senescence in prostate cancer via its transcriptional co-regulation of the CDKN1A (p21(WAF1) (/) (CIP1) ) and SIRT1 genes (PMID:25557355)
• Increased NR2E1 level may be closely associated with inflammation and disorder of lipid and glucose metabolism in diabetic patients. (PMID:25813674)
• TLX has a role in regulating growth and invasion in ERalpha-negative breast cancer cells (PMID:26280373)
• TLX biological role in mental illness and gliomagenesis (PMID:26554934)
• TLX downregulation induces TET3 expression and inhibits glioblastoma tumorigenesis and self-renewal in glioblastoma stem cells. (PMID:26838672)
• TLX and miR-219 have an important role in both normal neurodevelopment and in schizophrenia patient iPSC-derived NSCs. TLX has a role in regulating microRNA processing, independent of its well-characterized role in transcriptional regulation. (PMID:26965827)
• The interaction between TLX and TGF-beta may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells. (PMID:27048878)
• ASK1 phosphorylated and stabilized TLX, which led induction of HIF-1alpha, and its downstream VEGF-A in an Akt dependent manner. (PMID:27890558)
• Tumorigenic effects of TLX overexpression in HEK 293T cells. (PMID:32721119)
• Genetic analysis of the NR2E1 gene as a candidate gene of schizophrenia. (PMID:32805587)
• Orphan nuclear receptor TLX promotes immunosuppression via its transcriptional activation of PD-L1 in glioma. (PMID:33858847)
• TLX, an Orphan Nuclear Receptor With Emerging Roles in Physiology and Disease. (PMID:34463725)
• The nuclear receptor TLX (NR2E1) inhibits growth and progression of triple- negative breast cancer. (PMID:35932893)
• A NR2E1-interacting peptide of LSD1 inhibits the proliferation of brain tumour initiating cells. (PMID:36321378)

Cross-species orthologs

26 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr2e1	ENSDARG00000017107
mus_musculus	Nr2e1	ENSMUSG00000019803
rattus_norvegicus	Nr2e1	ENSRNOG00000050550
drosophila_melanogaster	tll	FBGN0003720
caenorhabditis_elegans		WBGENE00003626
caenorhabditis_elegans		WBGENE00003650
caenorhabditis_elegans	nhr-69	WBGENE00003659
caenorhabditis_elegans		WBGENE00003683
caenorhabditis_elegans		WBGENE00003706
caenorhabditis_elegans		WBGENE00003719
caenorhabditis_elegans		WBGENE00003726
caenorhabditis_elegans		WBGENE00007547
caenorhabditis_elegans		WBGENE00008221
caenorhabditis_elegans		WBGENE00011097
caenorhabditis_elegans		WBGENE00011098
caenorhabditis_elegans		WBGENE00011099
caenorhabditis_elegans		WBGENE00011100
caenorhabditis_elegans		WBGENE00015395
caenorhabditis_elegans		WBGENE00015396
caenorhabditis_elegans		WBGENE00015397
caenorhabditis_elegans		WBGENE00015705
caenorhabditis_elegans		WBGENE00016975
caenorhabditis_elegans		WBGENE00017198
caenorhabditis_elegans		WBGENE00017787
caenorhabditis_elegans		WBGENE00020748
caenorhabditis_elegans		WBGENE00044354

Paralogs (11): HNF4A (ENSG00000101076), NR2C1 (ENSG00000120798), RXRG (ENSG00000143171), NR2F6 (ENSG00000160113), HNF4G (ENSG00000164749), NR2F1 (ENSG00000175745), NR2C2 (ENSG00000177463), NR2F2 (ENSG00000185551), RXRA (ENSG00000186350), RXRB (ENSG00000204231), NR2E3 (ENSG00000278570)

Protein

Protein identifiers

Nuclear receptor subfamily 2 group E member 1 — Q9Y466 (reviewed: Q9Y466)

Alternative names: Nuclear receptor TLX, Protein tailless homolog

All UniProt accessions (3): A6PVF6, B6ZGT9, Q9Y466

UniProt curated annotations — full annotation on UniProt →

Function. Orphan receptor that binds DNA as a monomer to hormone response elements (HRE) containing an extended core motif half-site sequence 5’-AAGGTCA-3’ in which the 5’ flanking nucleotides participate in determining receptor specificity. May be required to pattern anterior brain differentiation. Involved in the regulation of retinal development and essential for vision. During retinogenesis, regulates PTEN-Cyclin D expression via binding to the promoter region of PTEN and suppressing its activity. May be involved in retinoic acid receptor (RAR) regulation in retinal cells.

Subunit / interactions. Monomer. Interacts with ATN1; the interaction represses the transcription.

Subcellular location. Nucleus.

Tissue specificity. Brain specific. Present in all brain sections tested, highest levels in the caudate nucleus and hippocampus, weakest levels in the thalamus.

Similarity. Belongs to the nuclear hormone receptor family. NR2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y466-1	1	yes
Q9Y466-2	2

RefSeq proteins (2): NP_001273031, NP_003260* (*=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
IPR050274	Nuclear_hormone_rcpt_NR2	Family

Pfam: PF00104, PF00105

UniProt features (7 total): zinc finger region 2, chain 1, domain 1, DNA-binding region 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4XAJ	X-RAY DIFFRACTION	3.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y466-F1	77.89	0.53

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-8943724	Regulation of PTEN gene transcription

MSigDB gene sets: 291 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, ATF_B, GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, GOBP_DENTATE_GYRUS_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, MODULE_255, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, GCANCTGNY_MYOD_Q6, CMYB_01

GO Biological Process (47): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), behavioral fear response (GO:0001662), positive regulation of neuroblast proliferation (GO:0002052), aggressive behavior (GO:0002118), apoptotic process (GO:0006915), nervous system development (GO:0007399), neuroblast proliferation (GO:0007405), visual perception (GO:0007601), dentate gyrus development (GO:0021542), amygdala development (GO:0021764), olfactory bulb development (GO:0021772), layer formation in cerebral cortex (GO:0021819), cerebral cortex neuron differentiation (GO:0021895), anterior commissure morphogenesis (GO:0021960), cell differentiation (GO:0030154), extracellular matrix organization (GO:0030198), somatic stem cell population maintenance (GO:0035019), social behavior (GO:0035176), negative regulation of apoptotic process (GO:0043066), astrocyte cell migration (GO:0043615), cell fate commitment (GO:0045165), negative regulation of neuron differentiation (GO:0045665), positive regulation of angiogenesis (GO:0045766), positive regulation of cell cycle (GO:0045787), astrocyte differentiation (GO:0048708), negative regulation of astrocyte differentiation (GO:0048712), regulation of dendrite morphogenesis (GO:0048814), retina development in camera-type eye (GO:0060041), regulation of timing of neuron differentiation (GO:0060164), long-term synaptic potentiation (GO:0060291), regulation of cell migration involved in sprouting angiogenesis (GO:0090049), negative regulation of neural precursor cell proliferation (GO:2000178), positive regulation of stem cell proliferation (GO:2000648), regulation of DNA-templated transcription (GO:0006355), brain development (GO:0007420), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), forebrain generation of neurons (GO:0021872), central nervous system neuron differentiation (GO:0021953)

GO Molecular Function (15): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), histone deacetylase binding (GO:0042826), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), enzyme binding (GO:0019899), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Generic Transcription Pathway	1
PTEN Regulation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
anatomical structure development	3
DNA-binding transcription factor activity, RNA polymerase II-specific	3
regulation of transcription by RNA polymerase II	2
anatomical structure formation involved in morphogenesis	2
behavior	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
blood vessel morphogenesis	1
behavioral defense response	1
fear response	1
neuroblast proliferation	1
positive regulation of neurogenesis	1
regulation of neuroblast proliferation	1
positive regulation of neural precursor cell proliferation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
system development	1
generation of neurons	1
neural precursor cell proliferation	1
sensory perception of light stimulus	1
hippocampus development	1
limbic system development	1
olfactory lobe development	1
cerebral cortex radial glia-guided migration	1
forebrain neuron differentiation	1
telencephalon development	1
central nervous system projection neuron axonogenesis	1
cellular developmental process	1
extracellular structure organization	1
external encapsulating structure organization	1
stem cell population maintenance	1
biological process involved in intraspecies interaction between organisms	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1

Protein interactions and networks

STRING

1449 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR2E1	KDM1A	O60341	916
NR2E1	HDAC5	Q9UQL6	864
NR2E1	ATN1	P54259	825
NR2E1	GPR6	P46095	823
NR2E1	GRIK5	Q16478	796
NR2E1	NES	P48681	708
NR2E1	CRX	O43186	640
NR2E1	GRIK2	Q13002	595
NR2E1	FN1	P02751	582
NR2E1	FOXG1	P55315	581
NR2E1	GFAP	P14136	573
NR2E1	ASCL1	P50553	504
NR2E1	RS1	O15537	495
NR2E1	PTEN	P60484	494
NR2E1	PAX6	P26367	493

IntAct

14 interactions, top by confidence:

A	B	Type	Score
NR2E1	KDM1A	psi-mi:“MI:0914”(association)	0.680
NR2E1	KDM1A	psi-mi:“MI:2364”(proximity)	0.680
NR2E1	KDM1A	psi-mi:“MI:0407”(direct interaction)	0.680
NR2E1	KDM1A	psi-mi:“MI:0915”(physical association)	0.680
KDM1A	KDM1A	psi-mi:“MI:0915”(physical association)	0.660
NR2E1	SMARCA4	psi-mi:“MI:0914”(association)	0.480
NR2E1	SMARCA4	psi-mi:“MI:2364”(proximity)	0.480
NR2E1	SMARCA4	psi-mi:“MI:0403”(colocalization)	0.480
SCRIB	NR2E1	psi-mi:“MI:0915”(physical association)	0.400
NR2E1	DCAF6	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): DCAF6 (Affinity Capture-MS), TNRC6C (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), IMPDH1 (Affinity Capture-MS), UPF3B (Affinity Capture-MS), C9orf41 (Affinity Capture-MS), GNB4 (Affinity Capture-MS), ARL10 (Affinity Capture-MS), SUFU (Affinity Capture-MS), TMSB10 (Affinity Capture-MS), CIZ1 (Affinity Capture-MS), MTDH (Affinity Capture-MS), VRK3 (Affinity Capture-MS), TWISTNB (Affinity Capture-MS), NR2E1 (Reconstituted Complex)

ESM2 similar proteins: O08580, O09017, O09018, P10588, P10589, P11474, P12813, P22736, P22829, P24468, P28702, P28704, P33242, P43135, P43136, P49743, P49870, P50569, P51666, P55055, P79387, Q04752, Q06725, Q06726, Q0V8F0, Q13133, Q13285, Q3U0S6, Q5BIS6, Q5E9B6, Q5QJV7, Q5TJF7, Q5U651, Q60632, Q60644, Q62755, Q64104, Q6PH18, Q6QMY5, Q90733

Diamond homologs: A2T928, A2T929, G5ECR9, O00482, O08580, O09017, O09018, O42101, O44960, O45666, O76202, O95718, P10276, P10588, P10589, P10826, P11416, P11474, P11475, P13631, P16375, P16376, P18514, P18516, P18911, P19793, P20153, P22448, P22449, P22605, P24468, P28699, P28700, P28701, P28702, P28704, P28705, P41235, P43135, P43136

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SOX2	“up-regulates quantity by expression”	NR2E1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1772 predictions. Top by Δscore:

Variant	Effect	Δscore
6:108173151:A:T	donor_gain	1.0000
6:108174834:AG:A	acceptor_gain	1.0000
6:108174835:GG:G	acceptor_gain	1.0000
6:108174835:GGGA:G	acceptor_gain	1.0000
6:108174920:GACG:G	donor_gain	1.0000
6:108176488:T:TA	acceptor_gain	1.0000
6:108176492:T:TA	acceptor_gain	1.0000
6:108176501:A:AG	acceptor_gain	1.0000
6:108176501:AGCC:A	acceptor_gain	1.0000
6:108176502:G:GT	acceptor_gain	1.0000
6:108176502:GC:G	acceptor_gain	1.0000
6:108176502:GCC:G	acceptor_gain	1.0000
6:108176502:GCCG:G	acceptor_gain	1.0000
6:108176789:G:T	donor_gain	1.0000
6:108178089:A:AG	acceptor_gain	1.0000
6:108178090:C:G	acceptor_gain	1.0000
6:108178090:CCCA:C	acceptor_loss	1.0000
6:108178091:CCA:C	acceptor_loss	1.0000
6:108178093:A:AG	acceptor_gain	1.0000
6:108178094:G:GA	acceptor_gain	1.0000
6:108178094:GT:G	acceptor_gain	1.0000
6:108178094:GTA:G	acceptor_gain	1.0000
6:108178094:GTAC:G	acceptor_gain	1.0000
6:108178094:GTACC:G	acceptor_gain	1.0000
6:108178241:GGTAT:G	donor_loss	1.0000
6:108178242:G:A	donor_loss	1.0000
6:108178243:T:A	donor_loss	1.0000
6:108180805:A:AG	acceptor_gain	1.0000
6:108180805:AG:A	acceptor_gain	1.0000
6:108180805:AGGC:A	acceptor_loss	1.0000

AlphaMissense

2497 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:108171478:T:A	C16S	1.000
6:108171478:T:C	C16R	1.000
6:108171479:G:A	C16Y	1.000
6:108171479:G:C	C16S	1.000
6:108171479:G:T	C16F	1.000
6:108171480:C:G	C16W	1.000
6:108171484:G:A	V18M	1.000
6:108171487:T:A	C19S	1.000
6:108171487:T:C	C19R	1.000
6:108171488:G:A	C19Y	1.000
6:108171488:G:C	C19S	1.000
6:108171488:G:T	C19F	1.000
6:108171489:T:G	C19W	1.000
6:108171493:G:C	D21H	1.000
6:108171494:A:C	D21A	1.000
6:108171494:A:G	D21G	1.000
6:108171494:A:T	D21V	1.000
6:108171499:A:C	S23R	1.000
6:108171500:G:A	S23N	1.000
6:108171500:G:T	S23I	1.000
6:108171501:C:A	S23R	1.000
6:108171501:C:G	S23R	1.000
6:108171502:T:C	S24P	1.000
6:108171503:C:T	S24L	1.000
6:108171505:G:A	G25R	1.000
6:108171505:G:C	G25R	1.000
6:108171505:G:T	G25W	1.000
6:108171506:G:A	G25E	1.000
6:108171506:G:C	G25A	1.000
6:108171506:G:T	G25V	1.000

dbSNP variants (sampled 300 via entrez): RS1000059805 (6:108187623 T>C,G), RS1000123856 (6:108178986 T>C), RS1000294231 (6:108179460 G>C,T), RS1000332505 (6:108174821 T>C), RS1000625705 (6:108174131 C>T), RS1000664800 (6:108173468 A>G), RS1000691750 (6:108169193 C>T), RS1000726147 (6:108181057 A>T), RS1000782749 (6:108182757 C>T), RS1000821992 (6:108173798 C>T), RS1000908764 (6:108173897 G>A), RS1001049092 (6:108187782 A>G,T), RS1001066629 (6:108188998 G>A,C,T), RS1001176578 (6:108167658 C>A,T), RS1001298014 (6:108168543 G>A,T)

Disease associations

OMIM: gene MIM:603849 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly	Limited	Autosomal dominant

Mondo (1): microcephaly (MONDO:0001149)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1961788 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 415,927 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL113	CAFFEINE	4	200,591
CHEMBL27	PROPRANOLOL	4	85,886
CHEMBL631	PROPAFENONE	4	12,711
CHEMBL779	TADALAFIL	4	23,417
CHEMBL275742	DEXPROPRANOLOL	2	15,667
CHEMBL452861	LEVOPROPRANOLOL	2	77,655

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 2E. Tailless-like receptors

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
BMS493	Agonist	7.27	pIC50
tretinoin	Agonist	5.74	pEC50
compound 10 [PMID: 34989568]	Agonist	5.72	pKd

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5277896	EC50	200 nM

ChEMBL bioactivities

44 potent at pChembl≥5 of 60 total, top 44 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	Kd	60	nM	CHEMBL5618909
7.05	EC50	90	nM	CHEMBL5618548
7.00	EC50	100	nM	CHEMBL5618740
6.96	Kd	110	nM	CHEMBL5619615
6.89	EC50	130	nM	CHEMBL5619500
6.85	EC50	140	nM	CHEMBL5618909
6.80	Kd	160	nM	CHEMBL5618740
6.70	EC50	200	nM	CHEMBL5277896
6.70	EC50	200	nM	CHEMBL2385268
6.70	EC50	200	nM	RETINAL
6.70	EC50	200	nM	CHEMBL5619514
6.66	EC50	220	nM	CHEMBL5618246
6.60	EC50	251.2	nM	CHEMBL5080383
6.60	EC50	250	nM	CHEMBL5080383
6.58	EC50	260	nM	CHEMBL5619615
6.44	Kd	360	nM	CHEMBL5619514
6.40	EC50	400	nM	CHEMBL5619484
6.30	Kd	500	nM	PROPRANOLOL
6.30	EC50	500	nM	CHEMBL5618230
6.30	EC50	500	nM	CHEMBL5618588
6.22	EC50	600	nM	CHEMBL5619493
6.16	EC50	700	nM	CHEMBL5080383
6.16	EC50	700	nM	CHEMBL5618438
6.16	EC50	700	nM	CHEMBL5620162
6.05	EC50	900	nM	CHEMBL5618094
6.05	EC50	900	nM	CHEMBL5618699
6.00	EC50	1000	nM	CHEMBL5090226
6.00	EC50	1000	nM	CHEMBL5618147
6.00	EC50	1000	nM	CHEMBL5620053
6.00	EC50	1000	nM	CHEMBL5619983
5.92	EC50	1200	nM	CHEMBL5089826
5.89	EC50	1300	nM	CHEMBL5618709
5.80	Kd	1600	nM	CHEMBL5080383
5.80	EC50	1600	nM	CHEMBL5619707
5.80	EC50	1600	nM	CHEMBL5619135
5.77	EC50	1700	nM	CHEMBL5618526
5.60	EC50	2500	nM	CHEMBL5620146
5.60	EC50	2500	nM	CHEMBL5620263
5.52	EC50	3000	nM	CHEMBL5088898
5.30	EC50	5000	nM	TADALAFIL
5.30	EC50	5000	nM	CHEMBL5071695
5.30	EC50	5000	nM	CHEMBL5080383
5.10	IC50	7943	nM	CAFFEINE
5.10	EC50	8000	nM	CHEMBL5618097

PubChem BioAssay actives

44 with measured affinity, of 184 total; 36 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
2-(2-chlorophenyl)-N-[3-(2-methyl-4-pyridinyl)-5-(trifluoromethyl)phenyl]acetamide	2130364: Binding affinity to human TLX LBD assessed as dissociation constant by ITC analysis	kd	0.0600	uM
2-(2,6-dichlorophenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.0900	uM
N-[3-[(1,5-dimethylpyrazole-3-carbonyl)amino]-5-(trifluoromethyl)phenyl]quinoline-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.1000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]quinoline-4-carboxamide	2130364: Binding affinity to human TLX LBD assessed as dissociation constant by ITC analysis	kd	0.1100	uM
2-butoxy-N-[3-(4-methylimidazol-1-yl)phenyl]quinoline-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.1300	uM
2-(2-chlorophenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.2000	uM
(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenal	1925149: Inverse agonist activity at TLX (unknown origin)	ec50	0.2000	uM
4-[(E)-2-(5,5-dimethyl-8-phenyl-6H-naphthalen-2-yl)ethenyl]benzoic acid	1925149: Inverse agonist activity at TLX (unknown origin)	ec50	0.2000	uM
4-[7-(1-adamantyl)-6-hydroxynaphthalen-2-yl]benzoic acid	1925149: Inverse agonist activity at TLX (unknown origin)	ec50	0.2000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]naphthalene-1-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.2200	uM
2-butoxy-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]quinoline-4-carboxamide	1821778: Agonist activity at human Gal4-fused TLX LBD expressed in human HEK293T cells coexpressing Gal4-VP16 assessed as repressor activity of receptor by measuring decrease in reporter activity measured after 14 hrs by Dual-Glo Luciferase assay	ec50	0.2500	uM
N-[3-(2-methyl-4-pyridinyl)-5-(trifluoromethyl)phenyl]quinoline-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.4000	uM
N-[3-(benzimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-butoxyquinoline-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.5000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-[2-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.5000	uM
Propranolol	1810687: Binding affinity to TLX LBD expressed in His6-tagged Escherichia coli Rosetta assessed as binding constant measured after 300 sec at 200 mM by isothermal titration calorimetry	kd	0.5000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-phenylacetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.6000	uM
3-butoxy-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]naphthalene-1-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.7000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-1H-indole-3-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.7000	uM
2-(2-cyanophenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.9000	uM
2-(2,4-dichlorophenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	0.9000	uM
2-(4-chlorophenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	1.0000	uM
2-(2,3-dichlorophenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	1.0000	uM
N-[3-[[2-(2-chlorophenyl)acetyl]amino]-5-(trifluoromethyl)phenyl]-1,5-dimethylpyrazole-3-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	1.0000	uM
(4-benzhydrylpiperazin-1-yl)-(1,5-dimethylpyrazol-3-yl)methanone	1821778: Agonist activity at human Gal4-fused TLX LBD expressed in human HEK293T cells coexpressing Gal4-VP16 assessed as repressor activity of receptor by measuring decrease in reporter activity measured after 14 hrs by Dual-Glo Luciferase assay	ec50	1.0000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-4-(4-phenylphenyl)butanamide	1821778: Agonist activity at human Gal4-fused TLX LBD expressed in human HEK293T cells coexpressing Gal4-VP16 assessed as repressor activity of receptor by measuring decrease in reporter activity measured after 14 hrs by Dual-Glo Luciferase assay	ec50	1.2000	uM
2-butoxy-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]pyridine-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	1.3000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-oxo-1H-quinoline-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	1.6000	uM
2-(3-chlorophenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]acetamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	1.6000	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-phenylpropanamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	1.7000	uM
2-butoxy-N-[3-(dimethylamino)-5-(trifluoromethyl)phenyl]quinoline-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	2.5000	uM
2-methoxy-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]pyridine-4-carboxamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	2.5000	uM
4-amino-5-chloro-2-methoxy-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide	1821778: Agonist activity at human Gal4-fused TLX LBD expressed in human HEK293T cells coexpressing Gal4-VP16 assessed as repressor activity of receptor by measuring decrease in reporter activity measured after 14 hrs by Dual-Glo Luciferase assay	ec50	3.0000	uM
Tadalafil	1810681: Agonist activity at in human TLX LBD expressed in human HEK293T cells coexpressing Gal4-VP 16 assessed as increase in reporter activity measured after 14 hrs by luciferase reporter gene assay relative to control	ec50	5.0000	uM
4-(4-hydroxyphenyl)-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]piperazine-1-carboxamide	1821778: Agonist activity at human Gal4-fused TLX LBD expressed in human HEK293T cells coexpressing Gal4-VP16 assessed as repressor activity of receptor by measuring decrease in reporter activity measured after 14 hrs by Dual-Glo Luciferase assay	ec50	5.0000	uM
Caffeine	1920739: Inhibition of tlx (unknown origin)	ic50	7.9433	uM
N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]benzamide	2130362: Agonist activity at human TLX LBD expressed in HEK293T cells co-transfected with RL/Gal4-VP16 assessed as repression of VP16-induced reporter activity incubated for 16 hrs by Dual-Glo Luciferase assay	ec50	8.0000	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	6
trichostatin A	affects cotreatment, decreases expression	3
Vorinostat	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
tetrachlorodian	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Amphotericin B	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Silicon Dioxide	increases expression	1
Copper Sulfate	increases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

109 unique, capped per target: 109 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1961850	Binding	Effect on TLX(NR2E1) dependent reporter activity in HEK293 cells at 20 uM	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — Nature

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4U8	SEES3-1V human NR2E1, clone1	Embryonic stem cell	Male
CVCL_A4U9	SEES3-1V human NR2E1, clone2	Embryonic stem cell	Male
CVCL_A4V0	SEES3-1V human NR2E1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.