CXCL16

Summary

CXCL16 (C-X-C motif chemokine ligand 16, HGNC:16642) is a protein-coding gene on chromosome 17p13.2, encoding C-X-C motif chemokine 16 (Q9H2A7). Acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis.

Enables chemokine activity. Involved in several processes, including positive regulation of cell growth; response to tumor necrosis factor; and response to type II interferon. Located in extracellular space. Biomarker of COVID-19 and systemic scleroderma.

Source: NCBI Gene 58191 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001386809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16642
Approved symbol	CXCL16
Name	C-X-C motif chemokine ligand 16
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	SR-PSOX, CXCLG16, SRPSOX
Ensembl gene	ENSG00000161921
Ensembl biotype	protein_coding
OMIM	605398
Entrez	58191

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000293778, ENST00000573123, ENST00000574412, ENST00000575168, ENST00000576153, ENST00000886021, ENST00000886022, ENST00000886023

RefSeq mRNA: 2 — MANE Select: NM_001386809 NM_001100812, NM_001386809

CCDS: CCDS11052

Canonical transcript exons

ENST00000293778 — 6 exons

Exon	Start	End
ENSE00003993646	4735092	4735508
ENSE00003993647	4739261	4739928
ENSE00003993648	4734583	4734652
ENSE00003993649	4738782	4738920
ENSE00003993650	4738408	4738490
ENSE00003993754	4733533	4734479

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1097 / max 2031.4739, expressed in 1403 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163959	10.5581	1169
163952	5.3804	880
163957	5.0679	516
163943	2.4962	284
163948	2.3841	238
163954	1.2179	255
163950	0.5390	191
163951	0.4653	173
163960	0.3533	172
163956	0.2742	122

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.56	gold quality
right testis	UBERON:0004534	97.53	gold quality
gall bladder	UBERON:0002110	97.45	gold quality
right lung	UBERON:0002167	96.77	gold quality
upper lobe of left lung	UBERON:0008952	96.05	gold quality
upper lobe of lung	UBERON:0008948	95.87	gold quality
vermiform appendix	UBERON:0001154	95.76	gold quality
testis	UBERON:0000473	94.48	gold quality
islet of Langerhans	UBERON:0000006	94.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.08	gold quality
monocyte	CL:0000576	93.82	gold quality
leukocyte	CL:0000738	93.81	gold quality
lower lobe of lung	UBERON:0008949	93.58	gold quality
minor salivary gland	UBERON:0001830	93.03	gold quality
blood	UBERON:0000178	92.86	gold quality
rectum	UBERON:0001052	92.71	gold quality
spleen	UBERON:0002106	92.67	gold quality
ileal mucosa	UBERON:0000331	92.42	gold quality
lung	UBERON:0002048	92.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.04	gold quality
palpebral conjunctiva	UBERON:0001812	91.97	gold quality
oviduct epithelium	UBERON:0004804	91.64	gold quality
right coronary artery	UBERON:0001625	91.54	gold quality
nasal cavity epithelium	UBERON:0005384	91.36	gold quality
mouth mucosa	UBERON:0003729	91.11	gold quality
lower esophagus mucosa	UBERON:0035834	90.92	gold quality
granulocyte	CL:0000094	90.77	gold quality
spinal cord	UBERON:0002240	90.73	gold quality
epithelial cell of pancreas	CL:0000083	90.71	gold quality
saliva-secreting gland	UBERON:0001044	90.50	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	1599.71
E-HCAD-13	yes	1420.10
E-MTAB-8142	yes	97.53
E-CURD-122	yes	72.64
E-MTAB-6701	yes	62.40
E-HCAD-4	yes	57.78
E-MTAB-10553	yes	42.98
E-MTAB-6678	yes	42.64
E-GEOD-84465	yes	37.26
E-GEOD-134144	yes	31.73
E-MTAB-10287	yes	23.41
E-HCAD-1	yes	21.04
E-CURD-88	yes	19.95
E-CURD-112	yes	13.33
E-MTAB-8410	yes	12.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOS, JUN

miRNA regulators (miRDB)

52 targeting CXCL16, 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-12118	100.00	65.88	1270
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-6731-5P	99.28	67.42	2375

Literature-anchored findings (GeneRIF, showing 40)

• SR-PSOX/CXCL16 may play an important role in facilitating uptake of various pathogens and chemotaxis of T and NKT cells by antigen presenting cells through its chemokine domain. (PMID:12902461)
• CXCL16 may play an important role in the development and progression of atherosclerotic vascular disease (PMID:14625285)
• SR-PSOX/CXCL16 is a unique molecule that not only attracts T cells and NKT cells toward DCs but also supports their firm adhesion to DCs. (PMID:14634054)
• SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4 activation and stimulation of IFN-[gamma] production by CD8+ T cells during inflammatory valvular heart disease. (PMID:14699018)
• This chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion. (PMID:14988089)
• This report demonstrates that CXCL16 is a novel substrate for a disintegrin and metalloproteinase domain (ADAM)10-mediated ectodomain shedding. (PMID:15128827)
• Smooth muscle cells express CXCL16 in atherosclerotic lesions, which may play a role in the attraction of T cells to atherosclerotic lesions and contribute to the cellular internalisation of modified LDL. (PMID:15555552)
• CXCL16 promotes lymphocyte adhesion to epithelial cells and may function to attract and retain effector cells that support biliary and hepatocyte destruction in inflammatory liver disease. (PMID:15634930)
• CXCL16 may act as a novel angiogenic factor for HUVEC and that ERK is involved as an important signaling molecule to mediate its angiogenic effects (PMID:15883016)
• Transmembrane chemokine CXCL16 is expressed in the brain by malignant and inflamed astroglial cells, shed to a soluble form and targets not only activated T cells but also glial cells themselves. (PMID:15934948)
• Findings suggest that retinoid signaling might be a pathway modulating inflammatory response by regulating CXCL16 expression in a cell-specific manner. (PMID:16142401)
• CXCL16 plays an important role in T cell accumulation and stimulation in rheumatoid arthritis synovium (PMID:16200580)
• CXCL16 plays important roles in human extravillous cytotrophoblast invasion and placentation. (PMID:16431903)
• The membrane-bound scavenger receptor CXCL16 expressed on the surface of plasmacytoid dendritic cells contributes to the binding, uptake, and stimulatory activity of D class CpG oligonucleotides. (PMID:16849465)
• evaluate the contribution of soluble CXCL16 to the scavenging of oxLDL and its potential as a marker for cardiovascular disease in patients with rheumatoid arthritis (PMID:17300746)
• CXCL16 is constitutively expressed on the surface of human epidermal keratinocytes, released upon cell activation or photodamage and may then target CXCR6-expressing T cells in the dermis (PMID:17363916)
• Bacterial infection causes the upregulation of CXCL16 in gallbladder epithelia, leading to the chemoattraction of macrophages via CXCL16-CXCR6 interaction and formation of the characteristic histology of xanthogranulomatous cholecystitis. (PMID:17803654)
• The CXCL16 is a novel mediator of the innate immune reactivities of epidermal keratinocytes. (PMID:17855433)
• Hyperhomocysteinemia up-regulates CXCL16 leading to increased recruitment of CXCR6(+) lymphocytes and scavenging of modified lipids via a potential involvement of a PPAR-gamma-dependent mechanism (PMID:18194461)
• Re-expression of CXCL16 reduced growth of an RCC cell line in vitro. (PMID:18195710)
• in Crohn’s disease (CD), the CXCL16 p.Ala181Val polymorphism is not a disease susceptibility gene but associated with younger age at disease onset and higher frequency of ileal involvement (PMID:18248772)
• Functions as one of the factors in trophoblast-conditioned culture medium that interacts with CXCR6 and recruits and maintains monocytes, T cells, and gammadelta T cells residing in human decidua. (PMID:18250446)
• Increased level of serum-soluble CXCL16 was independently associated with acute coronary syndromes (PMID:18279707)
• CXCL16 appears to be a novel growth factor for schwannomas of different localization. (PMID:18293410)
• Soluble CXCL16 could be linked to atherogenesis not only as a marker of inflammation, but also as a potential inflammatory mediator. (PMID:18339644)
• CXCL16 functions, through CXCR6, as a novel chemotactic factor for prostate cancer cells. (PMID:18344492)
• The regulation and functional role of CXCL16 in human mesangial cells was studied. (PMID:18373975)
• CXCL16 and ADAM10 are involved in the recruitment of T cells to the kidney (PMID:18480749)
• CXCL16 levels in the acute coronary syndrome group were higher than controls and stable angina pectoris group (PMID:18514099)
• sirna decreased the expression of the SRPSOX gene by inhibiting macrophage-derived foam cell formation (PMID:18565283)
• CXCL16 seems to play an important role in the pathobiology of pancreatic cancer (PMID:18636150)
• CXCR6 and CXCR3 act coordinately with respective ligands and are involved in the pathophysiology of Juvenile Idiopathic Arthritis-associated inflammatory processes. (PMID:18760678)
• data demonstrate that downregulation of CXCL16 plays an important role in renal cancer development and progression, and that CXCL16 in renal cell carcinoma is an independent prognostic marker for better patient survival (PMID:19070478)
• bronchial epithelial cells secreted relatively high basal levels of CXCL16, chemotactic for CXCR6 expressing T cells from blood (PMID:19415545)
• regulation of CXCL16, ADAM10 and oxLDL expression may be an early event in the onset of diabetic nephropathy (PMID:19426159)
• we presume important roles for CXCL16, ADAM10, and ADAM17 in the development of membranous nephropathy (PMID:19435795)
• CXCL16 mediates atheroprotection through its scavenger role in macrophages and not by cell-cell adhesion (PMID:19494317)
• In patients with an acute coronary syndrome, CXCL16 levels obtained within 24 hours of admission are associated with long-term mortality after adjustment for other risk factors (PMID:19528340)
• Myofibroblastic hepatic stellate cells release soluble Hedgehog ligands that stimulate cholangiocytes to produce Cxcl16 and recruit NKT cells. (PMID:19575365)
• CXCL16 levels were increased in patients with systemic sclerosis, and correlated with the extent of skin sclerosis, suggesting that CXCL16 may have a role in the development of skin fibrosis in systemic sclerosis. (PMID:19605674)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cxcl16	ENSMUSG00000018920
rattus_norvegicus	Cxcl16	ENSRNOG00000026647

Protein

Protein identifiers

C-X-C motif chemokine 16 — Q9H2A7 (reviewed: Q9H2A7)

Alternative names: Scavenger receptor for phosphatidylserine and oxidized low density lipoprotein, Small-inducible cytokine B16, Transmembrane chemokine CXCL16

All UniProt accessions (3): A0A6I8PIU7, Q9H2A7, I3L333

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a scavenger receptor on macrophages, which specifically binds to OxLDL (oxidized low density lipoprotein), suggesting that it may be involved in pathophysiology such as atherogenesis. Induces a strong chemotactic response. Induces calcium mobilization. Binds to CXCR6/Bonzo.

Subcellular location. Cell membrane. Secreted.

Tissue specificity. Expressed in T-cell areas. Expressed in spleen, lymph nodes, lung, kidney, small intestine and thymus. Weak expression in heart and liver and no expression in brain and bone marrow.

Post-translational modifications. Glycosylated.

Similarity. Belongs to the intercrine alpha (chemokine CxC) family.

RefSeq proteins (2): NP_001094282, NP_001373738* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026296	CXCL16	Family
IPR048585	CXCL16_dom	Domain

Pfam: PF20902

UniProt features (18 total): sequence conflict 4, region of interest 4, disulfide bond 2, sequence variant 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2A7-F1	65.77	0.26

Functional residue map

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

Disulfide bonds (2): 38–68, 40–82

Glycosylation sites (1): 168

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 226 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_GROWTH, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GAURNIER_PSMD4_TARGETS, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_LEUKOCYTE_CHEMOTAXIS, CREB_Q4

GO Biological Process (10): receptor-mediated endocytosis (GO:0006898), chemotaxis (GO:0006935), T cell chemotaxis (GO:0010818), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), response to cytokine (GO:0034097), response to type II interferon (GO:0034341), response to tumor necrosis factor (GO:0034612), signal transduction (GO:0007165), lymphocyte chemotaxis (GO:0048247)

GO Molecular Function (4): low-density lipoprotein particle receptor activity (GO:0005041), scavenger receptor activity (GO:0005044), chemokine activity (GO:0008009), cytokine activity (GO:0005125)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to cytokine	2
cellular anatomical structure	2
endocytosis	1
response to chemical	1
taxis	1
lymphocyte chemotaxis	1
T cell migration	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
response to peptide	1
innate immune response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
leukocyte chemotaxis	1
lymphocyte migration	1
low-density lipoprotein particle binding	1
lipoprotein particle receptor activity	1
cargo receptor activity	1
cytokine activity	1
chemokine receptor binding	1
cell chemotaxis	1
receptor ligand activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL16	CXCR6	O00574	999
CXCL16	CCRL2	O00421	976
CXCL16	CCR6	P51684	975
CXCL16	CXCR3	P49682	945
CXCL16	CX3CR1	P49238	926
CXCL16	CXCL6	P80162	855
CXCL16	CCR5	P51681	839
CXCL16	CX3CL1	P78423	833
CXCL16	CXCL1	P09341	817
CXCL16	CXCR4	P30991	813
CXCL16	CXCR1	P25024	812
CXCL16	CXCL9	Q07325	808
CXCL16	CXCL10	P02778	790
CXCL16	CCL5	P13501	785
CXCL16	CXCR2	P25025	781

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CXCL16	SCAMP1	psi-mi:“MI:0914”(association)	0.350
CXCL16	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
SLC46A3	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): CXCL16 (Two-hybrid), CXCL16 (Two-hybrid), CXCL16 (Two-hybrid), CXCL16 (Two-hybrid), CCDC155 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), TMEM239 (Two-hybrid), CXCL16 (Synthetic Lethality), CXCL16 (Two-hybrid), CXCL16 (Two-hybrid), CXCL16 (Two-hybrid)

ESM2 similar proteins: A0A1B0GU29, A6NLX4, A6QNY1, A9CBA0, B7ZWI3, O14669, O88472, P14784, P16297, P25918, P26896, Q0VFL4, Q13651, Q32M26, Q38J84, Q38J85, Q3SYS8, Q58CT8, Q5BK39, Q5EAA5, Q5HZE8, Q5NCP0, Q5RCL0, Q64322, Q68DV7, Q6AXS2, Q6AXU5, Q6NUJ2, Q6UWV7, Q86UW2, Q8BHB3, Q8BLR5, Q8BSU2, Q8C353, Q8C708, Q8K1T1, Q8MII8, Q8N6P7, Q8NET5, Q8R182

Diamond homologs: Q29RT9, Q6AXU5, Q8BSU2, Q9GKE2, Q9H2A7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
hsa-miR-451a	“down-regulates quantity by repression”	CXCL16	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

831 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4734594:T:TA	donor_gain	1.0000
17:4735505:CATT:C	acceptor_gain	1.0000
17:4734581:AC:A	donor_gain	0.9900
17:4734582:CC:C	donor_gain	0.9900
17:4734588:CAAG:C	donor_gain	0.9900
17:4735086:GTTTA:G	donor_loss	0.9900
17:4735087:TTTA:T	donor_loss	0.9900
17:4735088:TTACC:T	donor_loss	0.9900
17:4735089:TACC:T	donor_loss	0.9900
17:4735090:ACC:A	donor_loss	0.9900
17:4735091:CCT:C	donor_loss	0.9900
17:4735506:ATTCT:A	acceptor_loss	0.9900
17:4735507:TT:T	acceptor_gain	0.9900
17:4735508:TCTG:T	acceptor_loss	0.9900
17:4735509:C:CC	acceptor_gain	0.9900
17:4735509:C:T	acceptor_loss	0.9900
17:4738402:TCTCA:T	donor_loss	0.9900
17:4738403:CTCA:C	donor_loss	0.9900
17:4738404:TCA:T	donor_loss	0.9900
17:4738405:CACC:C	donor_loss	0.9900
17:4738407:C:CT	donor_loss	0.9900
17:4738489:ACC:A	acceptor_loss	0.9900
17:4738491:CT:C	acceptor_loss	0.9900
17:4738492:T:C	acceptor_loss	0.9900
17:4738847:CGA:C	acceptor_gain	0.9900
17:4738848:G:T	acceptor_gain	0.9900
17:4739256:CTAA:C	donor_loss	0.9900
17:4739257:TAA:T	donor_loss	0.9900
17:4739259:A:AT	donor_loss	0.9900
17:4739260:C:CT	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000094385 (17:4738000 C>T), RS1000529707 (17:4737224 T>G), RS1000693154 (17:4739775 G>A,C), RS1001903939 (17:4733481 G>C), RS1002086062 (17:4740818 A>G,T), RS1002103817 (17:4741029 C>G,T), RS1003115937 (17:4739867 GGA>G), RS1003321275 (17:4734920 G>A), RS1003859044 (17:4741420 C>A,T), RS1003918797 (17:4736365 G>A), RS1004117828 (17:4738583 G>A), RS1004370614 (17:4736653 C>T), RS1004592174 (17:4740195 C>G), RS1004606929 (17:4733599 CAA>C), RS1004749670 (17:4733866 T>A)

Disease associations

OMIM: gene MIM:605398 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006585_2232	Blood protein levels	2.000000e-09
GCST009731_10	Blood protein levels in cardiovascular risk	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008044	C-C motif chemokine 16 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	4
Benzene	affects expression, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression, affects expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Smoke	decreases expression	2
Tretinoin	increases secretion, increases expression	2
Valproic Acid	increases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
nickel chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
incobotulinumtoxinA	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Mustard Gas	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
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NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
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NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
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NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
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NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
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NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
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NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
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NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia