NDNF

Summary

NDNF (neuron derived neurotrophic factor, HGNC:26256) is a protein-coding gene on chromosome 4q27, encoding Protein NDNF (Q8TB73). Secretory protein that plays a role in various cellular processes.

Predicted to enable heparin binding activity. Involved in several processes, including cellular response to hypoxia; negative regulation of apoptotic process; and nitric oxide mediated signal transduction. Located in extracellular region. Is active in extracellular space. Implicated in hypogonadotropic hypogonadism.

Source: NCBI Gene 79625 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypogonadotropic hypogonadism 25 with anosmia (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 78 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 48
• MANE Select transcript: NM_024574

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26256
Approved symbol	NDNF
Name	neuron derived neurotrophic factor
Location	4q27
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23191
Ensembl gene	ENSG00000173376
Ensembl biotype	protein_coding
OMIM	616506
Entrez	79625

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000379692, ENST00000506900, ENST00000511408, ENST00000515757, ENST00000871774, ENST00000871775, ENST00000871776, ENST00000871777, ENST00000871778, ENST00000871779, ENST00000871780, ENST00000959904, ENST00000959905

RefSeq mRNA: 1 — MANE Select: NM_024574 NM_024574

CCDS: CCDS3717

Canonical transcript exons

ENST00000379692 — 4 exons

Exon	Start	End
ENSE00001205012	121071993	121072535
ENSE00001611953	121039930	121040054
ENSE00001740431	121035613	121037657
ENSE00001784917	121045650	121045838

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 98.75.

FANTOM5 (CAGE): breadth broad, TPM avg 17.9120 / max 1285.4304, expressed in 646 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53789	12.4746	571
53790	4.6953	439
53788	0.7421	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal glomerulus	UBERON:0000074	98.75	gold quality
metanephric glomerulus	UBERON:0004736	98.61	gold quality
visceral pleura	UBERON:0002401	97.41	gold quality
lower lobe of lung	UBERON:0008949	96.04	gold quality
periodontal ligament	UBERON:0008266	93.79	gold quality
choroid plexus epithelium	UBERON:0003911	93.38	gold quality
lung	UBERON:0002048	93.30	gold quality
right lung	UBERON:0002167	92.30	gold quality
bronchial epithelial cell	CL:0002328	92.11	gold quality
tibia	UBERON:0000979	90.45	gold quality
upper lobe of lung	UBERON:0008948	90.35	gold quality
upper lobe of left lung	UBERON:0008952	89.94	gold quality
kidney epithelium	UBERON:0004819	89.03	gold quality
tendon of biceps brachii	UBERON:0008188	88.38	gold quality
epithelium of bronchus	UBERON:0002031	88.20	gold quality
mucosa of urinary bladder	UBERON:0001259	88.03	gold quality
bronchus	UBERON:0002185	87.29	gold quality
metanephros	UBERON:0000081	85.80	gold quality
placenta	UBERON:0001987	85.35	gold quality
left ovary	UBERON:0002119	85.18	gold quality
calcaneal tendon	UBERON:0003701	85.03	gold quality
adult organism	UBERON:0007023	85.01	gold quality
tendon	UBERON:0000043	84.81	gold quality
germinal epithelium of ovary	UBERON:0001304	83.66	gold quality
ovary	UBERON:0000992	83.64	gold quality
right uterine tube	UBERON:0001302	83.20	gold quality
right ovary	UBERON:0002118	82.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.48	gold quality
medial globus pallidus	UBERON:0002477	82.03	gold quality
layer of synovial tissue	UBERON:0007616	81.79	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.54
E-GEOD-130148	yes	6.07
E-HCAD-30	no	54.07
E-ENAD-27	no	3.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

miRNA regulators (miRDB)

84 targeting NDNF, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-106B-5P	99.88	74.72	2795

Literature-anchored findings (GeneRIF, showing 5)

• direct duplication of chromosome 4q27q31.3 de novo results in partial trisomy of its long arm. (PMID:16970039)
• NDNF acts as an endogenous modulator that promotes endothelial cell function and ischemia-induced revascularization through eNOS-dependent mechanisms (PMID:24706764)
• Secretome profiling identifies neuron-derived neurotrophic factor as a tumor-suppressive factor in lung cancer. (PMID:31852841)
• Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism. (PMID:31883645)
• Overexpression of NDNF Improves the Cytoprotective Effects of Aged Human Bone Marrow Mesenchymal Stem Cells by Modulating Oxidative Stress and Apoptosis. (PMID:38801165)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnf	ENSDARG00000062936
mus_musculus	Ndnf	ENSMUSG00000049001
rattus_norvegicus	Ndnf	ENSRNOG00000006857
drosophila_melanogaster	nord	FBGN0050418
caenorhabditis_elegans		WBGENE00021893

Protein

Protein identifiers

Protein NDNF — Q8TB73 (reviewed: Q8TB73)

Alternative names: Neuron-derived neurotrophic factor

All UniProt accessions (3): D6R972, D6RF18, Q8TB73

UniProt curated annotations — full annotation on UniProt →

Function. Secretory protein that plays a role in various cellular processes. Acts as a chemorepellent acting on gonadotropin-releasing hormone (GnRH) expressing neurons regulating their migration to the hypothalamus. Also promotes neuron migration, growth and survival as well as neurite outgrowth and is involved in the development of the olfactory system. May also act through the regulation of growth factors activity and downstream signaling. Also regulates extracellular matrix assembly and cell adhesiveness. Promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization through NOS3-dependent mechanisms.

Subunit / interactions. Binds heparin and chondroitin sulfate.

Subcellular location. Secreted.

Tissue specificity. Expressed in neurons along the gonadotropin-releasing hormone (GnRH) expressing neurons migratory route.

Post-translational modifications. O-glycosylated; contains heparan sulfate and chondroitin sulfate. N-glycosylated.

Disease relevance. Hypogonadotropic hypogonadism 25 with anosmia (HH25) [MIM:618841] A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone, and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). HH25 is an autosomal dominant form with anosmia, characterized by intrafamilial variable expressivity and incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by hypoxia (at protein level).

RefSeq proteins (1): NP_078850* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR019326	NDNF	Family
IPR036116	FN3_sf	Homologous_superfamily
IPR045805	NDNF_C	Domain
IPR055271	NDNF_Fn(III)_1	Domain
IPR056225	NDNF_N	Domain

Pfam: PF10179, PF19433, PF24354

UniProt features (9 total): sequence variant 3, domain 2, signal peptide 1, chain 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TB73-F1	78.58	0.44

Functional residue map

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

Glycosylation sites (1): 322

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 272 (showing top): GOBP_FOREBRAIN_NEURON_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GCANCTGNY_MYOD_Q6, GOBP_NEUROGENESIS, CHX10_01, AAAYRNCTG_UNKNOWN, CHANDRAN_METASTASIS_DN, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_WOUND_HEALING, GOBP_HYPOTHALAMUS_DEVELOPMENT, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS

GO Biological Process (14): angiogenesis (GO:0001525), neuron migration (GO:0001764), response to ischemia (GO:0002931), obsolete nitric oxide mediated signal transduction (GO:0007263), positive regulation of cell-substrate adhesion (GO:0010811), positive regulation of neuron projection development (GO:0010976), gonadotrophin-releasing hormone neuronal migration to the hypothalamus (GO:0021828), extracellular matrix organization (GO:0030198), negative regulation of neuron apoptotic process (GO:0043524), cellular response to fibroblast growth factor stimulus (GO:0044344), vascular wound healing (GO:0061042), cellular response to hypoxia (GO:0071456), negative regulation of endothelial cell apoptotic process (GO:2000352), nervous system development (GO:0007399)

GO Molecular Function (3): glycosaminoglycan binding (GO:0005539), heparin binding (GO:0008201), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of apoptotic process	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell migration	1
generation of neurons	1
response to stress	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
neuron migration	1
hypothalamic tangential migration using cell-axon interactions	1
hypothalamus gonadotrophin-releasing hormone neuron development	1
extracellular structure organization	1
external encapsulating structure organization	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
cellular response to growth factor stimulus	1
response to fibroblast growth factor	1
angiogenesis involved in wound healing	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
endothelial cell apoptotic process	1
regulation of endothelial cell apoptotic process	1
system development	1
carbohydrate derivative binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDNF	LHB	P01229	608
NDNF	FSHB	P01225	592
NDNF	IL17RD	Q8NFM7	583
NDNF	LAMP5	Q9UJQ1	540
NDNF	HS6ST1	O60243	480
NDNF	SLC10A4	Q96EP9	443
NDNF	PARM1	Q6UWI2	402
NDNF	FGF17	O60258	398
NDNF	LHX6	Q9UPM6	379
NDNF	SEMA3A	Q14563	372
NDNF	SNCG	O76070	364
NDNF	RFTN1	Q14699	360
NDNF	CDV3	Q9UKY7	349
NDNF	RELN	P78509	337
NDNF	VTA1	Q9NP79	336

IntAct

15 interactions, top by confidence:

A	B	Type	Score
NDNF	SSR3	psi-mi:“MI:0915”(physical association)	0.400
NDNF	EFHD1	psi-mi:“MI:0915”(physical association)	0.400
NDNF	MDM2	psi-mi:“MI:0915”(physical association)	0.400
FADD	NUP42	psi-mi:“MI:0914”(association)	0.350
TNIP1	COCH	psi-mi:“MI:0914”(association)	0.350
TNIP2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
ANOS1	ZNF724	psi-mi:“MI:0914”(association)	0.350
CCL4L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
C1QTNF7	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), SSR3 (Proximity Label-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), EFHD1 (Affinity Capture-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), NDNF (Affinity Capture-MS), MDM2 (Affinity Capture-MS)

ESM2 similar proteins: A4IIK7, A8K855, B5MFE9, D3Z2R5, E7F240, F1QPX0, F1R520, O94985, P03970, P07995, P08476, P10600, P17125, P18331, P23352, P27092, P33005, P43032, P55102, Q04998, Q08761, Q0VCN6, Q15198, Q2PFX1, Q5BIP2, Q5R2I8, Q5R2J4, Q5R9Q9, Q5RJP7, Q66KI8, Q68CR1, Q6DF34, Q6GNK9, Q6PE55, Q6Q0N0, Q6X2S4, Q7T2L7, Q7Z494, Q80TS8, Q8BR86

Diamond homologs: A4IIK7, F1QPX0, Q6GNK9, Q8C119, Q8TB73

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	59
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
834069	NM_024574.4(NDNF):c.184A>T (p.Lys62Ter)	Pathogenic
834070	NM_024574.4(NDNF):c.381del (p.Tyr128fs)	Pathogenic
834071	NM_024574.4(NDNF):c.1406G>A (p.Trp469Ter)	Pathogenic
1709811	NM_024574.4(NDNF):c.1159del (p.Ile387fs)	Likely pathogenic
3385370	NM_024574.4(NDNF):c.1009G>T (p.Glu337Ter)	Likely pathogenic
4292410	NM_024574.4(NDNF):c.551_552del (p.Val184fs)	Likely pathogenic

SpliceAI

646 predictions. Top by Δscore:

Variant	Effect	Δscore
4:121037658:C:CC	acceptor_gain	1.0000
4:121037658:CTA:C	acceptor_loss	1.0000
4:121037659:T:A	acceptor_loss	1.0000
4:121039924:GCTTA:G	donor_loss	1.0000
4:121039925:CTTA:C	donor_loss	1.0000
4:121039926:TTA:T	donor_loss	1.0000
4:121039927:TA:T	donor_loss	1.0000
4:121039928:A:AC	donor_gain	1.0000
4:121039928:A:T	donor_loss	1.0000
4:121039929:C:CC	donor_gain	1.0000
4:121039929:C:CT	donor_loss	1.0000
4:121040050:AATAC:A	acceptor_gain	1.0000
4:121040051:ATAC:A	acceptor_gain	1.0000
4:121040052:TAC:T	acceptor_gain	1.0000
4:121040053:AC:A	acceptor_gain	1.0000
4:121040053:ACC:A	acceptor_loss	1.0000
4:121040054:CC:C	acceptor_gain	1.0000
4:121040055:C:CC	acceptor_gain	1.0000
4:121040055:CT:C	acceptor_loss	1.0000
4:121040056:T:C	acceptor_loss	1.0000
4:121045676:A:C	donor_gain	1.0000
4:121037654:TCAC:T	acceptor_gain	0.9900
4:121037655:CAC:C	acceptor_gain	0.9900
4:121037655:CACC:C	acceptor_gain	0.9900
4:121037656:AC:A	acceptor_gain	0.9900
4:121037657:CC:C	acceptor_gain	0.9900
4:121045649:CCT:C	donor_gain	0.9900
4:121045707:G:T	donor_gain	0.9900
4:121045704:A:AC	donor_gain	0.9800
4:121045705:C:CC	donor_gain	0.9800

AlphaMissense

3745 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:121036566:A:G	W469R	0.999
4:121036566:A:T	W469R	0.999
4:121037385:A:G	W196R	0.999
4:121037385:A:T	W196R	0.999
4:121039981:A:G	W88R	0.999
4:121039981:A:T	W88R	0.999
4:121036564:C:A	W469C	0.998
4:121036564:C:G	W469C	0.998
4:121036568:G:T	A468D	0.998
4:121036302:A:C	Y557D	0.997
4:121036337:A:T	V545D	0.997
4:121037302:A:C	S223R	0.997
4:121037302:A:T	S223R	0.997
4:121037304:T:G	S223R	0.997
4:121037535:A:C	Y146D	0.997
4:121039999:A:G	C82R	0.997
4:121040013:A:T	V77D	0.997
4:121036604:A:C	F456C	0.996
4:121039974:A:G	L90P	0.996
4:121039979:C:A	W88C	0.996
4:121039979:C:G	W88C	0.996
4:121039998:C:T	C82Y	0.996
4:121036535:C:G	C479S	0.995
4:121036536:A:G	C479R	0.995
4:121036536:A:T	C479S	0.995
4:121037298:A:G	C225R	0.995
4:121037374:G:C	S199R	0.995
4:121037374:G:T	S199R	0.995
4:121037376:T:G	S199R	0.995
4:121037383:C:A	W196C	0.995

dbSNP variants (sampled 300 via entrez): RS1000034372 (4:121048237 C>G,T), RS1000088347 (4:121051530 T>C), RS1000089708 (4:121038438 T>C), RS1000190836 (4:121072419 G>A,T), RS1000213819 (4:121068863 C>T), RS1000374861 (4:121065599 G>A,C), RS1000471761 (4:121072761 C>G,T), RS1000653522 (4:121067652 T>C), RS1000683992 (4:121036952 T>G), RS1000684422 (4:121062473 T>C), RS1000707793 (4:121067287 C>T), RS1000753093 (4:121035301 G>A,T), RS1000774326 (4:121065988 A>G,T), RS1000807877 (4:121074246 C>G), RS1000820252 (4:121062176 G>C)

Disease associations

OMIM: gene MIM:616506 | disease phenotypes: MIM:618841

GenCC curated gene-disease

Disease	Classification	Inheritance
hypogonadotropic hypogonadism 25 with anosmia	Strong	Autosomal dominant
Kallmann syndrome	Supportive	Autosomal dominant

Mondo (2): hypogonadotropic hypogonadism 25 with anosmia (MONDO:0030010), Kallmann syndrome (MONDO:0018800)

Orphanet (0):

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000054	Micropenis
HP:0000104	Renal agenesis
HP:0000144	Decreased fertility
HP:0000175	Cleft palate
HP:0000407	Sensorineural hearing impairment
HP:0000458	Anosmia
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000551	Color vision defect
HP:0000639	Nystagmus
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000823	Delayed puberty
HP:0000830	Anterior hypopituitarism
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001335	Bimanual synkinesia
HP:0001337	Tremor
HP:0001513	Obesity
HP:0001608	Abnormality of the voice
HP:0001761	Pes cavus
HP:0001763	Pes planus

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	5
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Nickel	decreases expression	2
Oxygen	decreases reaction, increases expression	2
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression	1
testosterone enanthate	affects expression	1
arsenite	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	affects expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Vorinostat	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT00064987	PHASE2	TERMINATED	Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
NCT00392756	PHASE1	COMPLETED	Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
NCT00493961	PHASE1	COMPLETED	Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism
NCT00914823	PHASE1	COMPLETED	Kisspeptin Administration in the Adult
NCT01438034	PHASE1	COMPLETED	Kisspeptin in the Evaluation of Delayed Puberty
NCT03118479	PHASE1	TERMINATED	Effect of Varying Testosterone Levels on Insulin Sensitivity in Men With Idiopathic Hypogonadotropic Hypogonadism (IHH)
NCT00392457	Not specified	COMPLETED	Investigating the Regulation of Reproductive Hormones in Adult Men
NCT00494169	Not specified	COMPLETED	Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders
NCT00623116	Not specified	UNKNOWN	A Study to Characterize Epidemiology, Clinical and Genetic Features of Kallmann Syndrome in Finland
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01914172	Not specified	COMPLETED	Health Needs of Patients With Kallmann Syndrome
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04733274	Not specified	ACTIVE_NOT_RECRUITING	Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing
NCT05971836	Not specified	ACTIVE_NOT_RECRUITING	The Molecular Basis of Inherited Reproductive Disorders