POU6F2

Summary

POU6F2 (POU class 6 homeobox 2, HGNC:21694) is a protein-coding gene on chromosome 7p14.1, encoding POU domain, class 6, transcription factor 2 (P78424). Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells.

This gene encodes a member of the POU protein family characterized by the presence of a bipartite DNA binding domain, consisting of a POU-specific domain and a homeodomain, separated by a variable polylinker. The DNA binding domain may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner. The POU family members are transcriptional regulators, many of which are known to control cell type-specific differentiation pathways. This gene is a tumor suppressor involved in Wilms tumor (WT) predisposition. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 11281 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Wilms tumor 5 (Limited, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 166 total — 2 pathogenic
• Phenotypes (HPO): 29
• MANE Select transcript: NM_001370959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21694
Approved symbol	POU6F2
Name	POU class 6 homeobox 2
Location	7p14.1
Locus type	gene with protein product
Status	Approved
Aliases	RPF-1
Ensembl gene	ENSG00000106536
Ensembl biotype	protein_coding
OMIM	609062
Entrez	11281

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 protein_coding

ENST00000403058, ENST00000416452, ENST00000426456, ENST00000451021, ENST00000464276, ENST00000517348, ENST00000518318, ENST00000520104, ENST00000524147, ENST00000673818, ENST00000673891, ENST00000674059

RefSeq mRNA: 3 — MANE Select: NM_001370959 NM_001166018, NM_001370959, NM_007252

CCDS: CCDS94088

Canonical transcript exons

ENST00000518318 — 10 exons

Exon	Start	End
ENSE00001368697	39406600	39406740
ENSE00003504055	39339642	39340015
ENSE00003544809	39085860	39086031
ENSE00003568832	39204235	39204326
ENSE00003576818	39460547	39460715
ENSE00003647499	39207392	39207620
ENSE00003788254	39451533	39451701
ENSE00003791423	39433077	39433283
ENSE00003897669	38977909	38978058
ENSE00003897871	39464182	39468601

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 80.17.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3294 / max 29.0184, expressed in 91 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78241	0.1948	68
78239	0.0565	41
78235	0.0422	25
78240	0.0360	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.47	gold quality
ventricular zone	UBERON:0003053	69.29	gold quality
prefrontal cortex	UBERON:0000451	68.42	gold quality
islet of Langerhans	UBERON:0000006	67.23	gold quality
sural nerve	UBERON:0015488	67.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.44	gold quality
cortical plate	UBERON:0005343	63.87	gold quality
frontal cortex	UBERON:0001870	63.69	gold quality
ganglionic eminence	UBERON:0004023	63.62	gold quality
neocortex	UBERON:0001950	63.00	gold quality
primary visual cortex	UBERON:0002436	62.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.30	gold quality
pancreas	UBERON:0001264	61.55	gold quality
right frontal lobe	UBERON:0002810	61.42	gold quality
buccal mucosa cell	CL:0002336	60.96	gold quality
endometrium epithelium	UBERON:0004811	60.73	gold quality
anterior cingulate cortex	UBERON:0009835	60.24	gold quality
cerebral cortex	UBERON:0000956	59.45	gold quality
gall bladder	UBERON:0002110	59.30	gold quality
superior frontal gyrus	UBERON:0002661	58.44	gold quality
body of pancreas	UBERON:0001150	58.25	gold quality
postcentral gyrus	UBERON:0002581	58.21	silver quality
occipital lobe	UBERON:0002021	58.18	gold quality
right lobe of liver	UBERON:0001114	57.66	gold quality
frontal pole	UBERON:0002795	57.13	gold quality
parietal lobe	UBERON:0001872	55.65	silver quality
amygdala	UBERON:0001876	55.42	gold quality
vena cava	UBERON:0004087	55.39	gold quality
pigmented layer of retina	UBERON:0001782	55.24	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	649.77
E-HCAD-35	yes	74.67
E-GEOD-81608	yes	14.98
E-ANND-3	yes	6.77
E-ENAD-27	no	8.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CDKN2A
CYP19A1
NF1
TYR

JASPAR motifs

Motif	Name	Family
MA0793.1	POU6F2	POU domain factors
MA0793.2	POU6F2	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:9852081

miRNA regulators (miRDB)

4 targeting POU6F2, 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-6885-3P	99.75	70.36	3187
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-1289	97.46	65.37	655

Literature-anchored findings (GeneRIF, showing 6)

• observations suggest that POU6F2 is a tumor suppressor and is involved in hereditary predisposition to Wilms tumor (PMID:15459955)
• Retina-derived POU domain factor 1 coordinates expression of genes relevant to renal and neuronal development (PMID:27425396)
• We further discovered that the expression of transcription factor POU class 6 homeobox 2 (POU6F2) is restricted to Corneal endothelial cells (CECs) , and upregulated during human CEC differentiation, suggesting that POU6F2 is pivotal to terminal differentiation of CECs (PMID:29113774)
• Genomic loci were examined in the NEIGHBORHOOD database to determine if they are potential risk factors for human glaucoma identified using meta-data from human GWAS. The top 50 hits all resided within one gene (POU6F2), with the highest significance level of p = 10-6 for SNP rs76319873. POU6F2 is found in retinal ganglion cells and in corneal limbal stem cells. (PMID:29370175)
• Whole-genome sequencing identified two novel somatic mutations in the POU6F2 gene (c. 839 C>T; c. 875A>G) in patients with prolactinoma. The mutations obviously decreased the expression level of POU6F2. Inhibition its activity increased the cell proliferation and PRL secretion in pituitary tumor cell line, but proliferation and PRL secretion were decreased in cells with POU6F2 overexpression. (PMID:31692290)
• POU6F2 mutation in humans with pubertal failure alters GnRH transcript expression. (PMID:37600690)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pou6f2	ENSDARG00000086362
mus_musculus	Pou6f2	ENSMUSG00000009734
rattus_norvegicus	AABR07027925.1	ENSRNOG00000013237
drosophila_melanogaster	acj6	FBGN0000028
caenorhabditis_elegans		WBGENE00006818

Paralogs (17): POU2F2 (ENSG00000028277), POU1F1 (ENSG00000064835), POU4F3 (ENSG00000091010), POU2F3 (ENSG00000137709), POU2F1 (ENSG00000143190), POU4F2 (ENSG00000151615), POU4F1 (ENSG00000152192), HDX (ENSG00000165259), POU6F1 (ENSG00000184271), POU3F2 (ENSG00000184486), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), POU3F3 (ENSG00000198914), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

POU domain, class 6, transcription factor 2 — P78424 (reviewed: P78424)

Alternative names: Retina-derived POU domain factor 1

All UniProt accessions (4): P78424, A0A669KBB9, A0A6E1XZL4, H7C2B2

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells. Recognizes and binds to the DNA sequence 5’-ATGCAAAT-3’. Isoform 1 does not bind DNA.

Subcellular location. Nucleus.

Tissue specificity. Expressed only within the CNS, where its expression is restricted to the medical habenulla, to a dispersed population of neurons in the dorsal hypothalamus, and to subsets of ganglion and amacrine cells in the retina.

Disease relevance. Hereditary susceptibility to Wilms tumor 5 (WT5) [MIM:601583] Pediatric malignancy of kidney and one of the most common solid cancers in childhood. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Major isoform.

Similarity. Belongs to the POU transcription factor family. Class-6 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P78424-1	1	yes
P78424-2	2

RefSeq proteins (3): NP_001159490, NP_001357888, NP_009183 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000327	POU_dom	Domain
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR013847	POU	Domain
IPR050255	POU_domain_TF	Family

Pfam: PF00046, PF00157

UniProt features (20 total): compositionally biased region 7, sequence variant 4, region of interest 3, sequence conflict 2, chain 1, domain 1, splice variant 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78424-F1	48.31	0.08

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): CAR_TNFRSF25, MORF_MSH3, MODULE_255, MORF_BRCA1, MORF_ATRX, MODULE_317, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MORF_RAD51L3, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, MORF_IL4, MORF_PRKCA, CAR_MLANA, GOBP_SENSORY_PERCEPTION, GATA4_Q3, MORF_ATF2

GO Biological Process (5): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), ganglion mother cell fate determination (GO:0007402), central nervous system development (GO:0007417), visual perception (GO:0007601)

GO Molecular Function (5): 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 factor activity (GO:0003700), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
cell fate determination	1
nervous system development	1
system development	1
sensory perception of light stimulus	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU6F2	OBSCN	Q5VST9	772
POU6F2	WT1	P19544	768
POU6F2	AMER1	Q5JTC6	740
POU6F2	RP9	Q8TA86	582
POU6F2	REST	Q13127	506
POU6F2	GPC3	P51654	491
POU6F2	PALM3	A6NDB9	438
POU6F2	CNGA1	P29973	438
POU6F2	IRX2	Q9BZI1	433
POU6F2	SLC6A2	P23975	398
POU6F2	THSD4	Q6ZMP0	398
POU6F2	COBL	O75128	391
POU6F2	GLRA1	P23415	391
POU6F2	IFIT1B	Q5T764	387
POU6F2	ADAMTS12	P58397	386
POU6F2	MICU1	Q9BPX6	386

IntAct

433 interactions, top by confidence:

A	B	Type	Score
POU6F2	PLAAT1	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	AGR2	psi-mi:“MI:0915”(physical association)	0.560
PROP1	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
POU6F2	PIBF1	psi-mi:“MI:0915”(physical association)	0.000
FNDC3B	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
TCEA2	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
MYO15B	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
ZFHX2	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
CDC23	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
HOXC5	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
CSNK2A1	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
TNPO2	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
HSPA4	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
TLX2	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
OPLAH	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
CDC37	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
STRA8	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
AIRIM	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
TBX6	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
POLR3C	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
MAPK9	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
XPOT	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
POU6F2	FOSB	psi-mi:“MI:0915”(physical association)	0.000
THADA	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
TTC23	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
KLHL11	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
CCNC	POU6F2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (148): POU6F2 (Affinity Capture-RNA), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid), POU6F2 (Two-hybrid)

ESM2 similar proteins: A2VE44, A7YY54, O00268, O00287, O35274, O35779, O75398, O77562, O77638, O88450, O95644, P12755, P15066, P17535, P17544, P22670, P48377, P52909, P78424, Q07916, Q13469, Q14863, Q3UR85, Q5R9C9, Q60591, Q69Z61, Q6R891, Q6T4P5, Q86YP4, Q8BJI4, Q8CHY6, Q8CIE2, Q8NF64, Q8R0S1, Q8R3B7, Q8TEK3, Q8VCG9, Q8VHR5, Q8WXI9, Q96N64

Diamond homologs: A0A1L8FFY5, A1L0Z1, A7Y7W2, B3DM23, B3DM25, B7ZQA9, D3ZTL1, G3V7L5, O97552, P09086, P10036, P10037, P13528, P14859, P15143, P16143, P16241, P17208, P20263, P20264, P20265, P20266, P20267, P20268, P20912, P20913, P20914, P21952, P24350, P25425, P28069, P31360, P31361, P31362, P31363, P31364, P31365, P31367, P31368, P31369

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	120
Likely benign	23
Benign	11

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1871	NM_001370959.1(POU6F2):c.660G>T (p.Gln220His)	Pathogenic
1872	NM_001370959.1(POU6F2):c.62C>G (p.Ser21Ter)	Pathogenic

SpliceAI

4465 predictions. Top by Δscore:

Variant	Effect	Δscore
7:39041826:T:G	acceptor_gain	1.0000
7:39085848:C:A	acceptor_gain	1.0000
7:39085855:CCTAG:C	acceptor_gain	1.0000
7:39085856:CTA:C	acceptor_loss	1.0000
7:39085856:CTAG:C	acceptor_gain	1.0000
7:39085857:TAGG:T	acceptor_gain	1.0000
7:39085858:A:AG	acceptor_gain	1.0000
7:39085858:AG:A	acceptor_gain	1.0000
7:39085858:AGG:A	acceptor_loss	1.0000
7:39085858:AGGA:A	acceptor_gain	1.0000
7:39085859:G:A	acceptor_loss	1.0000
7:39085859:G:GT	acceptor_gain	1.0000
7:39085859:GG:G	acceptor_gain	1.0000
7:39086027:CTTCG:C	donor_gain	1.0000
7:39086030:CGGT:C	donor_loss	1.0000
7:39086032:G:GA	donor_loss	1.0000
7:39086032:G:GG	donor_gain	1.0000
7:39086033:TAAG:T	donor_loss	1.0000
7:39207390:A:AG	acceptor_gain	1.0000
7:39207391:G:GA	acceptor_gain	1.0000
7:39207391:GCC:G	acceptor_gain	1.0000
7:39207391:GCCA:G	acceptor_gain	1.0000
7:39433279:AGCAG:A	donor_loss	1.0000
7:39433280:GCAGG:G	donor_loss	1.0000
7:39433281:CAGG:C	donor_loss	1.0000
7:39433282:AG:A	donor_loss	1.0000
7:39433283:GG:G	donor_loss	1.0000
7:39433284:G:GC	donor_loss	1.0000
7:39433285:T:A	donor_loss	1.0000
7:39085840:A:AG	acceptor_gain	0.9900

AlphaMissense

4700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:39460603:T:C	F487L	1.000
7:39460604:T:C	F487S	1.000
7:39460604:T:G	F487C	1.000
7:39460605:T:A	F487L	1.000
7:39460605:T:G	F487L	1.000
7:39460606:G:C	A488P	1.000
7:39460607:C:A	A488D	1.000
7:39460615:T:C	F491L	1.000
7:39460616:T:C	F491S	1.000
7:39460617:T:A	F491L	1.000
7:39460617:T:G	F491L	1.000
7:39460618:A:G	K492E	1.000
7:39460619:A:T	K492I	1.000
7:39460620:A:C	K492N	1.000
7:39460620:A:T	K492N	1.000
7:39460625:G:C	R494P	1.000
7:39460627:C:A	R495S	1.000
7:39460628:G:C	R495P	1.000
7:39460631:T:A	L496Q	1.000
7:39460631:T:C	L496P	1.000
7:39460633:T:C	S497P	1.000
7:39460637:T:C	L498P	1.000
7:39460639:G:C	G499R	1.000
7:39460640:G:A	G499D	1.000
7:39460640:G:T	G499V	1.000
7:39460643:T:C	L500P	1.000
7:39460646:C:T	T501I	1.000
7:39460650:G:C	Q502H	1.000
7:39460650:G:T	Q502H	1.000
7:39460655:A:C	Q504P	1.000

dbSNP variants (sampled 300 via entrez): RS1000003365 (7:39304592 T>C), RS1000005792 (7:38979349 G>A), RS1000010822 (7:39125333 C>A), RS1000011876 (7:39349971 T>C), RS1000035735 (7:39252702 T>A,C), RS1000047829 (7:39161452 C>A), RS1000061709 (7:39444782 C>T), RS1000073265 (7:39303078 T>C), RS1000089257 (7:39396519 G>A,T), RS1000094872 (7:39211325 C>T), RS1000100919 (7:39081141 T>A,C), RS1000103163 (7:39073951 A>G), RS1000103558 (7:39164297 A>T), RS1000104392 (7:39447490 C>A,T), RS1000107703 (7:39072847 A>G)

Disease associations

OMIM: gene MIM:609062 | disease phenotypes: MIM:601583, MIM:147950

GenCC curated gene-disease

Disease	Classification	Inheritance
Wilms tumor 5	Limited	Unknown

Mondo (2): Wilms tumor 5 (MONDO:0011112), hypogonadotropic hypogonadism (MONDO:0018555)

Orphanet (2): Nephroblastoma (Orphanet:654), Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432)

HPO phenotypes

29 total (30 of 29 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000086	Ectopic kidney
HP:0000526	Aniridia
HP:0000822	Hypertension
HP:0001442	Typified by somatic mosaicism
HP:0001528	Hemihypertrophy
HP:0001824	Weight loss
HP:0001901	Polycythemia
HP:0001903	Anemia
HP:0001945	Fever
HP:0002027	Abdominal pain
HP:0002094	Dyspnea
HP:0002664	Neoplasm
HP:0002667	Nephroblastoma
HP:0002716	Lymphadenopathy
HP:0002896	Neoplasm of the liver
HP:0002907	Microscopic hematuria
HP:0003072	Hypercalcemia
HP:0005580	Duplication of renal pelvis
HP:0008330	Reduced von Willebrand factor activity
HP:0012587	Macroscopic hematuria
HP:0012871	Varicocele
HP:0031105	Abnormal uterus morphology
HP:0031500	Abdominal mass
HP:0033834	Malaise
HP:0100526	Neoplasm of the lung
HP:0000044	Hypogonadotropic hypogonadism

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002759_31	Motion sickness	7.000000e-09
GCST005829_14	Hand grip strength	2.000000e-12
GCST005830_21	Hand grip strength	5.000000e-14
GCST005830_55	Hand grip strength	1.000000e-08
GCST006394_11	Intraocular pressure	3.000000e-08
GCST006412_65	Intraocular pressure	1.000000e-10
GCST006951_46	Feeling hurt	6.000000e-09
GCST008529_14	Tea consumption	2.000000e-08
GCST009722_8	Glaucoma (multi-trait analysis)	9.000000e-09
GCST009725_73	Intraocular pressure	5.000000e-08
GCST010002_348	Refractive error	1.000000e-11
GCST010219_10	Attention deficit hyperactivity disorder (inattention symptoms)	2.000000e-08
GCST010988_153	Adult body size	2.000000e-10
GCST011124_20	Caffeine consumption from tea	2.000000e-09
GCST90011770_10	Glaucoma (primary open-angle)	6.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006928	motion sickness
EFO:0006941	grip strength measurement
EFO:0004695	intraocular pressure measurement
EFO:0009599	feeling emotionally hurt measurement
EFO:0010091	tea consumption measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536707	Wilms tumor and radial bilateral aplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation	2
bisphenol A	decreases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
belinostat	increases expression	1
bisphenol S	decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	affects methylation	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1
Magnetite Nanoparticles	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00328926	PHASE4	TERMINATED	Luveris® (Lutropin Alfa for Injection) in Women With Hypogonadotropic Hypogonadism (Luteinizing Hormone [LH] Less Than [<] 1.2 International Unit Per Liter [IU/L])
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT01454011	PHASE4	COMPLETED	The Effect of Testosterone Replacement on the High Density Lipoprotein Cholesterol Subgroups
NCT01601327	PHASE4	COMPLETED	Effects of Medications in Patients With Hypogonadism
NCT02310074	PHASE4	UNKNOWN	Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03490513	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Men With Hypogonadism
NCT04456296	PHASE4	COMPLETED	A Study of the Effect of Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism
NCT05205837	PHASE4	TERMINATED	A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
NCT00467870	PHASE3	COMPLETED	Long-term Safety Study of Intramuscular Injections of 750 mg and 1000 mg Testosterone Undecanoate in Hypogonadal Men
NCT00962637	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal™ Treatment in Men With Secondary Hypogonadism
NCT01067365	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Androxal Treatment in Men With Secondary Hypogonadism
NCT01532414	PHASE3	COMPLETED	Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
NCT01534208	PHASE3	COMPLETED	Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01709331	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adult Men With Hypogonadotropic Hypogonadism (HH) (P07937)
NCT01739582	PHASE3	COMPLETED	An Extension Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism
NCT01739595	PHASE3	COMPLETED	Phase III Study to Evaluate Morning Testosterone Normalization in Overweight Men With Secondary Hypogonadism
NCT01993212	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT01993225	PHASE3	COMPLETED	A Randomized, Double Blind, Placebo-Controlled, Multi-Center Phase III Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Testosterone and Sperm Concentration Following Treatment With 12.5 mg or 25 mg Androxal or AndroGel 1.62%
NCT02110368	PHASE3	COMPLETED	Bioequivalence Study of Test and Reference Testosterone Topical Gel, 1.62% Metered Pump in Testosterone Deficient Adult Male Subjects Under Fasting Conditions
NCT03019575	PHASE3	COMPLETED	Efficacy and Safety of Corifollitropin Alfa (MK-8962) in Combination With Human Chorionic Gonadotropin (hCG) in Adolescent Males With Hypogonadotropic Hypogonadism (HH) (MK-8962-043)
NCT06561594	PHASE3	NOT_YET_RECRUITING	To Evaluate Recombinant Human Follicle Stimulating Hormone-CTP Fusion Protein Injection or Placebo Combined With Chorionic Gonadotropin for Injection
NCT00193661	PHASE2	COMPLETED	Observation Study of T-Gel (1%) in Treatment of Adolescent Boys With Hypogonadism
NCT00383656	PHASE2	UNKNOWN	Pulsatile GnRH in Anovulatory Infertility
NCT00697814	PHASE2	COMPLETED	Clomiphene in Males With Prolactinomas and Persistent Hypogonadism
NCT00706719	PHASE2	COMPLETED	To Evaluate Sperm Parameters in Men With Secondary Hypogonadism Previously Treated With Topical Testosterone
NCT00911586	PHASE2	COMPLETED	Pharmacokinetic Study to Determine Time to Steady-state
NCT01155518	PHASE2	TERMINATED	Hypogonadism in Young Men With Type 2 Diabetes
NCT01191320	PHASE2	COMPLETED	Study to Evaluate the Efficacy of Androxal in Controlling Blood Glucose in Men With Type-2 Diabetes Mellitus
NCT01270841	PHASE2	COMPLETED	Normalization of Morning Testosterone Levels in Men With Secondary Hypogonadism
NCT01386606	PHASE2	COMPLETED	The Effect on Androxal Versus Androgel on Morning Testosterone in Men With Secondary Hypogonadism (Low Testosterone)
NCT01894308	PHASE2	NOT_YET_RECRUITING	A Dose Ranging Study to Examine TDS-Testosterone 5%
NCT02369796	PHASE2	TERMINATED	A Phase 2a Pharmacodynamic Study of TAK-448 in Participants With Hypogonadotropic Hypogonadism
NCT02443090	PHASE2	UNKNOWN	Safety and Efficacy Study of Oral Fispemifene for the Treatment of Sexual Dysfunction in Hypogonadal Men
NCT02651688	PHASE2	COMPLETED	A Multi-Center Study in Men With Acquired Hypogonadotropic Hypogonadism to Compare Changes in Body Composition and Metabolic Parameters With Diet and Exercise in Conjunction With Treatment With 12.5 mg or 25 mg Enclomiphene
NCT02730169	PHASE2	COMPLETED	Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism
NCT02733133	PHASE2	NOT_YET_RECRUITING	Product Transference Study of Testagen™ TDS®-Testosterone
NCT02908074	PHASE2	COMPLETED	A 6 Month Safety Extension Study of MBGS205
NCT03245827	PHASE2	TERMINATED	Hypogonadotropic Hypogonadism in Obese Young Males
NCT04189133	PHASE2	UNKNOWN	Rec-LH PD and Safety Profile in Hypogonadotropic Hypogonadism Men