NR6A1

Summary

NR6A1 (nuclear receptor subfamily 6 group A member 1, HGNC:7985) is a protein-coding gene on chromosome 9q33.3, encoding Nuclear receptor subfamily 6 group A member 1 (Q15406). Orphan nuclear receptor that binds to a response element containing the sequence 5’-TCAAGGTCA-3'.

This gene encodes an orphan nuclear receptor which is a member of the nuclear hormone receptor family. Its expression pattern suggests that it may be involved in neurogenesis and germ cell development. The protein can homodimerize and bind DNA, but in vivo targets have not been identified. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 2649 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 87 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 29
• Druggable target: yes
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_033334

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7985
Approved symbol	NR6A1
Name	nuclear receptor subfamily 6 group A member 1
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	GCNF1, RTR, CT150
Ensembl gene	ENSG00000148200
Ensembl biotype	protein_coding
OMIM	602778
Entrez	2649

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000344523, ENST00000373584, ENST00000416460, ENST00000475178, ENST00000487099, ENST00000880987, ENST00000924541

RefSeq mRNA: 4 — MANE Select: NM_033334 NM_001278546, NM_001410996, NM_001489, NM_033334

CCDS: CCDS35137, CCDS55340, CCDS65127, CCDS94481

Canonical transcript exons

ENST00000487099 — 10 exons

Exon	Start	End
ENSE00000983672	124733308	124733349
ENSE00000983678	124543802	124543857
ENSE00000983679	124540033	124540187
ENSE00000983681	124535878	124536132
ENSE00000983682	124526779	124526900
ENSE00000983683	124524721	124524873
ENSE00001155707	124554328	124554570
ENSE00001824346	124771020	124771311
ENSE00001893620	124517275	124522793
ENSE00003789815	124538092	124538319

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 94.43.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7435 / max 631.1291, expressed in 789 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102439	2.0354	198
102444	1.9394	469
102445	1.7687	617

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.43	gold quality
oocyte	CL:0000023	93.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.57	gold quality
secondary oocyte	CL:0000655	91.04	gold quality
buccal mucosa cell	CL:0002336	89.78	silver quality
testis	UBERON:0000473	84.80	gold quality
right testis	UBERON:0004534	84.09	gold quality
left testis	UBERON:0004533	83.93	gold quality
adrenal tissue	UBERON:0018303	78.58	gold quality
sperm	CL:0000019	78.14	silver quality
male germ cell	CL:0000015	77.18	silver quality
adult organism	UBERON:0007023	74.87	gold quality
left lobe of thyroid gland	UBERON:0001120	73.70	gold quality
parotid gland	UBERON:0001831	73.20	gold quality
right lobe of thyroid gland	UBERON:0001119	73.19	gold quality
thyroid gland	UBERON:0002046	73.14	gold quality
vastus lateralis	UBERON:0001379	72.96	gold quality
esophagus squamous epithelium	UBERON:0006920	72.69	silver quality
diaphragm	UBERON:0001103	72.15	gold quality
quadriceps femoris	UBERON:0001377	72.05	gold quality
blood	UBERON:0000178	71.31	gold quality
nasal cavity epithelium	UBERON:0005384	71.21	gold quality
sural nerve	UBERON:0015488	71.01	gold quality
endothelial cell	CL:0000115	70.98	gold quality
placenta	UBERON:0001987	70.33	gold quality
mucosa of transverse colon	UBERON:0004991	69.75	gold quality
epithelium of esophagus	UBERON:0001976	69.69	silver quality
epithelial cell of pancreas	CL:0000083	69.68	gold quality
jejunal mucosa	UBERON:0000399	69.35	gold quality
tongue squamous epithelium	UBERON:0006919	69.32	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	1657.29
E-GEOD-134144	yes	27.29
E-ANND-3	yes	6.61
E-MTAB-6524	no	401.79

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets.

Target	Regulation
BMP15	Unknown
CR1
DPEP1
FGF4
GDF9	Unknown
HCRT
MBD3
MBD6
MOS	Unknown
NR6A1
OXT
POU5F1	Unknown
PPARD	Unknown
PRM1
PRM2	Activation
TDGF1	Repression
UIMC1

JASPAR motifs

Motif	Name	Family
MA1541.1	NR6A1	GCNF-related receptors (NR6)
MA1541.2	NR6A1	GCNF-related receptors (NR6)

JASPAR matrix evidence (PMIDs): PMID:11578963

Upstream regulators (CollecTRI, top): NR6A1

miRNA regulators (miRDB)

328 targeting NR6A1, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996

Literature-anchored findings (GeneRIF, showing 12)

• RTR mRNA was expressed in the human placental choriocarcinoma cell lines BeWo, JAR, and JEG-3. (PMID:11969338)
• characterization of a novel nuclear protein, referred to as RAP80, that interacts with the retinoid-related testis-associated receptor (PMID:12080054)
• down-regulation of CREMtau-mediated gene expression by GCNF (PMID:15456763)
• These experiments confirmed that NR6A1 works as a regulator for hypocretin transcription. (PMID:21056546)
• Findings show a role for Gcnf as a regulator of iPS cell pluripotency gene expression. It also demonstrates that reactivation of the Gcnf gene may serve as a marker to distinguish completely reprogrammed iPS cells from incompletely pluripotent cells. (PMID:23495137)
• Our results show that cellular levels of NR6A1 are correlated with disease progression in prostate cancer. (PMID:23532770)
• the genes, and up-regulated 64% in undifferentiated hES cells. In addition, GCNF also showed a regulatory gene pattern that is different from RA treatment during hES cell differentiation (PMID:26769970)
• GCNF acts as a transcriptional repressor in the regulation of OCT4 gene expression through cooperative interaction with three NR binding elements in pluripotent NCCIT cells. (PMID:29057499)
• the role of NR6A1 in the lipogenesis in HepG2 cells (PMID:31315616)
• hsa_circ_001653 up-regulates NR6A1 expression and elicits gastric cancer progression by binding to microRNA-377. (PMID:33006200)
• Novel LAMC2 fusion protein has tumor-promoting properties in ovarian carcinoma. (PMID:34689384)
• Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma. (PMID:37903971)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nr6a1a	ENSDARG00000101508
mus_musculus	Nr6a1	ENSMUSG00000063972
rattus_norvegicus	Nr6a1	ENSRNOG00000013232
drosophila_melanogaster	Hr4	FBGN0264562

Protein

Protein identifiers

Nuclear receptor subfamily 6 group A member 1 — Q15406 (reviewed: Q15406)

Alternative names: Germ cell nuclear factor, Retinoid receptor-related testis-specific receptor

All UniProt accessions (4): Q15406, C9JDI9, F1D8S0, F1DAM1

UniProt curated annotations — full annotation on UniProt →

Function. Orphan nuclear receptor that binds to a response element containing the sequence 5’-TCAAGGTCA-3’. Acts as a regulator of embryonic stem cell pluripotency by mediating repression of POU5F1/OCT4: binds to the DR0 element within the POU5F1/OCT4 promoter and inhibits POU5F1/OCT4 expression during embryonic stem cell differentiation. Involved in the regulation of gene expression in germ cell development during gametogenesis.

Subunit / interactions. Homodimer. Interacts with UIMC1.

Subcellular location. Nucleus.

Tissue specificity. Shows highest expression in the germ cells of the adult testis.

Disease relevance. Oculovertebral syndrome (OVS) [MIM:621277] An autosomal dominant syndrome characterized by missing vertebrae in the thoracic and/or lumbar spine and uveal coloboma, a congenital ocular malformation caused by failure of the ventral optic fissure to close during early eye morphogenesis and usually considered on a phenotypic continuum with microphthalmia and anophthalmia. Some patients have congenital kidney abnormalities. OVS shows incomplete penetrance and variable expressivity. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nuclear hormone receptor family. NR6 subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
Q15406-1	1	yes
Q15406-2	2
Q15406-3	3
Q15406-4	4
Q15406-5	5

RefSeq proteins (4): NP_001265475, NP_001397925, NP_001480, NP_201591* (*=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
IPR050200	Nuclear_hormone_rcpt_NR3	Family

Pfam: PF00104, PF00105

UniProt features (28 total): binding site 8, sequence variant 4, region of interest 4, splice variant 3, compositionally biased region 2, sequence conflict 2, zinc finger region 2, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15406-F1	78.02	0.63

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 (8): 60; 63; 77; 80; 96; 102; 112; 115

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2892247	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-383280	Nuclear Receptor transcription pathway

MSigDB gene sets: 278 (showing top): VALK_AML_WITH_FLT3_ITD, RNGTGGGC_UNKNOWN, FXR_IR1_Q6, SHEPARD_BMYB_MORPHOLINO_UP, TAL1ALPHAE47_01, DARWICHE_PAPILLOMA_PROGRESSION_RISK, CHX10_01, FOXD3_01, CREB_Q4, YGACNNYACAR_UNKNOWN, E2F1DP1_01, E2F1DP2_01, ATF1_Q6, MYCMAX_01, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), gamete generation (GO:0007276), positive regulation of mesenchymal stem cell differentiation (GO:2000741), regulation of DNA-templated transcription (GO:0006355), intracellular receptor signaling pathway (GO:0030522), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (13): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity (GO:0001217), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), estrogen response element binding (GO:0034056), protein homodimerization activity (GO:0042803), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transcriptional regulation of pluripotent stem cells	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
DNA-binding transcription factor activity	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
sexual reproduction	1
multicellular organismal reproductive process	1
mesenchymal stem cell differentiation	1
positive regulation of stem cell differentiation	1
regulation of mesenchymal stem cell differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
intracellular signal transduction	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
chromatin	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
intracellular receptor signaling pathway	1
signaling receptor activity	1
ligand-modulated transcription factor activity	1
transition metal ion binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
identical protein binding	1
protein dimerization activity	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription regulator activity	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NR6A1	MUL1	Q969V5	952
NR6A1	ATP6V0A2	Q9Y487	887
NR6A1	DNMT3A	Q9Y6K1	743
NR6A1	UBE2D2	P51669	716
NR6A1	DNMT3B	Q9UBC3	682
NR6A1	VRTN	Q9H8Y1	615
NR6A1	POU5F1	P31359	511
NR6A1	PLAG1	Q6DJT9	495
NR6A1	LCORL	Q8N3X6	493
NR6A1	NR0B1	P51843	491
NR6A1	UIMC1	Q96RL1	452
NR6A1	NANOG	Q9H9S0	433
NR6A1	MC1R	Q01726	420
NR6A1	RARS1	P54136	401
NR6A1	GRIN2A	Q12879	400

IntAct

4 interactions, top by confidence:

A	B	Type	Score
EFNA4	NBAS	psi-mi:“MI:0914”(association)	0.350
PNKD	ADD1	psi-mi:“MI:0914”(association)	0.350
GNB5	NR6A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): NR6A1 (Reconstituted Complex), NR6A1 (Reconstituted Complex), UIMC1 (Reconstituted Complex), NR6A1 (Affinity Capture-MS), NR6A1 (Affinity Capture-MS), NR6A1 (Affinity Capture-RNA), NR6A1 (Two-hybrid), NCOA1 (Two-hybrid)

ESM2 similar proteins: A0JNE3, A0P8Z4, O00482, O42101, P06211, P06212, P13056, P19785, P28701, P28705, P35398, P37238, P45448, P48443, P49116, P49117, P49867, P51128, P51129, P51448, P55094, P57783, P70033, P79926, P81559, Q04913, Q0GFF6, Q0VC20, Q15406, Q26622, Q28CK1, Q505F1, Q5BJR8, Q5RCZ5, Q5REL6, Q64249, Q66J63, Q66JK1, Q6GN21, Q8VIJ4

Diamond homologs: A0JNE3, A0P8Z4, A2T928, A4IIG7, F1QJF4, F1QLY4, O01639, O09018, O18924, O18971, O35507, O62807, O77245, O88275, P10276, P10589, P10826, P11416, P13055, P13056, P13631, P16375, P16376, P17671, P18514, P18515, P18516, P18911, P22448, P22605, P24468, P28699, P31396, P33244, P35398, P37231, P37233, P37238, P41828, P41829

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	59
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
4073540	NM_033334.4(NR6A1):c.274C>T (p.Arg92Trp)	Pathogenic
4073541	NM_033334.4(NR6A1):c.1306C>T (p.Arg436Cys)	Pathogenic
4073542	NR6A1, 107-KB DEL	Pathogenic
4532114	NM_033334.4(NR6A1):c.637C>T (p.Gln213Ter)	Pathogenic
4728955	NM_033334.4(NR6A1):c.1055C>A (p.Ser352Ter)	Pathogenic
4759262	NM_033334.4(NR6A1):c.220A>T (p.Ile74Phe)	Likely pathogenic
4759264	NM_033334.4(NR6A1):c.844_851dup (p.Phe284fs)	Likely pathogenic
4759265	NM_033334.4(NR6A1):c.1355-2A>G	Likely pathogenic

SpliceAI

4459 predictions. Top by Δscore:

Variant	Effect	Δscore
9:124526774:CTCA:C	donor_loss	1.0000
9:124526775:TCACC:T	donor_loss	1.0000
9:124526776:CA:C	donor_loss	1.0000
9:124526777:A:AT	donor_loss	1.0000
9:124526778:C:CA	donor_loss	1.0000
9:124526896:TAAAT:T	acceptor_gain	1.0000
9:124526901:C:CC	acceptor_gain	1.0000
9:124535873:CTCAC:C	donor_loss	1.0000
9:124535874:TCACC:T	donor_loss	1.0000
9:124535875:CACCT:C	donor_loss	1.0000
9:124535876:A:AC	donor_gain	1.0000
9:124535877:C:CC	donor_gain	1.0000
9:124540189:T:C	acceptor_gain	1.0000
9:124540190:T:C	acceptor_gain	1.0000
9:124540190:T:TC	acceptor_gain	1.0000
9:124543855:TAG:T	acceptor_gain	1.0000
9:124543857:GC:G	acceptor_loss	1.0000
9:124543858:C:CC	acceptor_gain	1.0000
9:124543858:CTGGA:C	acceptor_loss	1.0000
9:124554326:AC:A	donor_gain	1.0000
9:124554327:CC:C	donor_gain	1.0000
9:124554327:CCCTT:C	donor_gain	1.0000
9:124733306:A:AC	donor_gain	1.0000
9:124733307:C:CC	donor_gain	1.0000
9:124771109:T:TA	donor_gain	1.0000
9:124522576:T:TA	donor_gain	0.9900
9:124522709:T:TA	donor_gain	0.9900
9:124524715:TGTTA:T	donor_loss	0.9900
9:124524716:GTTA:G	donor_loss	0.9900
9:124524717:TTA:T	donor_loss	0.9900

AlphaMissense

3164 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:124526787:A:G	L398P	1.000
9:124526801:T:A	K393N	1.000
9:124526801:T:G	K393N	1.000
9:124535987:A:G	W324R	1.000
9:124535987:A:T	W324R	1.000
9:124536001:A:G	L319P	1.000
9:124536056:A:G	W301R	1.000
9:124536056:A:T	W301R	1.000
9:124543827:C:A	R139L	1.000
9:124543827:C:G	R139P	1.000
9:124543830:C:T	G138D	1.000
9:124543831:C:G	G138R	1.000
9:124543833:C:T	G137E	1.000
9:124543839:A:G	M135T	1.000
9:124543845:T:A	D133V	1.000
9:124543846:C:G	D133H	1.000
9:124543850:T:A	R131S	1.000
9:124543850:T:G	R131S	1.000
9:124543851:C:A	R131I	1.000
9:124543851:C:G	R131T	1.000
9:124543852:T:C	R131G	1.000
9:124543854:A:C	I130S	1.000
9:124543854:A:G	I130T	1.000
9:124543854:A:T	I130N	1.000
9:124543855:T:A	I130F	1.000
9:124543857:G:T	A129D	1.000
9:124554328:C:G	A129P	1.000
9:124554338:C:A	M125I	1.000
9:124554338:C:G	M125I	1.000
9:124554338:C:T	M125I	1.000

dbSNP variants (sampled 300 via entrez): RS1000000745 (9:124643774 AAGAG>A,AAG,AAGAGAG,AAGAGAGAG), RS1000000913 (9:124639616 G>A,C,T), RS1000032972 (9:124686452 C>T), RS1000038977 (9:124769150 C>A), RS1000047676 (9:124596317 G>A), RS1000048488 (9:124639963 T>C), RS1000049977 (9:124728048 A>C,G), RS1000052289 (9:124601004 G>A), RS1000058003 (9:124692232 CCATT>C), RS1000060449 (9:124760393 G>A), RS1000068374 (9:124627324 A>G), RS1000081477 (9:124668420 G>A), RS1000106358 (9:124643224 G>A,C), RS1000125866 (9:124755341 G>A,T), RS1000145526 (9:124676994 T>C)

Disease associations

OMIM: gene MIM:602778 | disease phenotypes: MIM:621277

GenCC curated gene-disease

Mondo (2): oculovertebral syndrome (MONDO:0979866), isolated anophthalmia-microphthalmia syndrome (MONDO:0016764)

Orphanet (1): Isolated microphthalmia-anophthalmia-coloboma (Orphanet:2542)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000122	Unilateral renal agenesis
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000518	Cataract
HP:0000523	Subcapsular cataract
HP:0000545	Myopia
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000588	Optic disc coloboma
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000646	Amblyopia
HP:0000821	Hypothyroidism
HP:0001634	Mitral valve prolapse
HP:0002414	Spina bifida
HP:0002650	Scoliosis
HP:0003298	Spina bifida occulta
HP:0003577	Congenital onset
HP:0007787	Posterior subcapsular cataract
HP:0011958	Retinal perforation
HP:0012741	Unilateral cryptorchidism
HP:0031176	Absent thoracic vertebra
HP:0032551	Hemorrhoids
HP:0100019	Cortical cataract

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003993_44	Menarche (age at onset)	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1961793 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 6A. Germ cell nuclear factor receptors

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 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
(3R)-3-benzyl-7-bromo-4-[[2-(4-chlorophenyl)sulfanylphenyl]methyl]-1,3-dihydro-1,4-benzodiazepine-2,5-dione	1918011: Antagonist activity at GCNF (unknown origin) by luciferase reporter gene assay	ec50	7.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, affects expression	2
Valproic Acid	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
trichostatin A	affects expression	1
resorcinol	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
jinfukang	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Dexamethasone	increases expression	1
Diazinon	increases methylation	1
Diclofenac	affects expression	1
Diethylhexyl Phthalate	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	increases expression	1
Hydrocortisone	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Ozone	affects expression, increases abundance	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	affects binding, increases reaction, increases activity	1
Urethane	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1961871	Binding	Effect on GCNF(NR6A1) 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_A4X8	SEES3-1V human NR6A1, clone1	Embryonic stem cell	Male
CVCL_A4X9	SEES3-1V human NR6A1, clone2	Embryonic stem cell	Male
CVCL_A4Y0	SEES3-1V human NR6A1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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