FKBP6

Summary

FKBP6 (FKBP prolyl isomerase family member 6 (inactive), HGNC:3722) is a protein-coding gene on chromosome 7q11.23, encoding Inactive peptidyl-prolyl cis-trans isomerase FKBP6 (O75344). Has an essential role in spermatogenesis.

The protein encoded by this gene is a cis-trans peptidyl-prolyl isomerase that may function in immunoregulation and basic cellular processes involving protein folding and trafficking. This gene is located in a chromosomal region that is deleted in Williams-Beuren syndrome. Defects in this gene may cause male infertility. There are multiple pseudogenes for this gene located nearby on chromosome 7. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8468 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 77 (Strong, GenCC)
• Clinical variants (ClinVar): 53 total — 3 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_003602

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3722
Approved symbol	FKBP6
Name	FKBP prolyl isomerase family member 6 (inactive)
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	PPIase, FKBP36
Ensembl gene	ENSG00000077800
Ensembl biotype	protein_coding
OMIM	604839
Entrez	8468

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000252037, ENST00000413573, ENST00000429879, ENST00000431982, ENST00000437013, ENST00000442793, ENST00000445032, ENST00000648538

RefSeq mRNA: 4 — MANE Select: NM_003602 NM_001135211, NM_001281304, NM_001362789, NM_003602

CCDS: CCDS43595, CCDS47604, CCDS64670

Canonical transcript exons

ENST00000252037 — 9 exons

Exon	Start	End
ENSE00001709106	73328161	73328485
ENSE00001789798	73358181	73358625
ENSE00002464127	73329360	73329449
ENSE00002488357	73328575	73328692
ENSE00003480137	73330150	73330352
ENSE00003584836	73331657	73331776
ENSE00003614977	73342807	73342899
ENSE00003621661	73340638	73340832
ENSE00003791155	73341273	73341382

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 94.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0378 / max 42.4020, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79007	0.0248	4
79006	0.0130	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.47	gold quality
right testis	UBERON:0004534	94.37	gold quality
testis	UBERON:0000473	91.77	gold quality
sperm	CL:0000019	87.32	gold quality
male germ cell	CL:0000015	87.31	gold quality
oocyte	CL:0000023	87.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.61	gold quality
type B pancreatic cell	CL:0000169	85.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.67	gold quality
secondary oocyte	CL:0000655	83.52	gold quality
olfactory bulb	UBERON:0002264	81.51	gold quality
diaphragm	UBERON:0001103	81.16	gold quality
adult organism	UBERON:0007023	80.53	gold quality
vena cava	UBERON:0004087	78.52	gold quality
tongue squamous epithelium	UBERON:0006919	73.55	gold quality
body of tongue	UBERON:0011876	72.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.71	gold quality
pharyngeal mucosa	UBERON:0000355	72.06	gold quality
myocardium	UBERON:0002349	71.97	gold quality
tongue	UBERON:0001723	71.74	gold quality
subthalamic nucleus	UBERON:0001906	71.39	gold quality
nasal cavity epithelium	UBERON:0005384	71.37	gold quality
cardia of stomach	UBERON:0001162	71.29	gold quality
ventral tegmental area	UBERON:0002691	70.94	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.91	gold quality
inferior vagus X ganglion	UBERON:0005363	70.85	gold quality
nipple	UBERON:0002030	70.55	gold quality
pericardium	UBERON:0002407	70.47	gold quality
dorsal plus ventral thalamus	UBERON:0001897	70.44	gold quality
saphenous vein	UBERON:0007318	70.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.35
E-GEOD-110499	no	24.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting FKBP6, 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-4534	99.99	66.58	1907
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-6795-3P	91.86	63.00	218

Literature-anchored findings (GeneRIF, showing 6)

• 278A polymorphism of FKBP6 gene was associated with idiopathic azoospermia, while C/T, 370G/A, 430G/C, 467T/C, 468G/A polymorphisms might be very rare in Chinese population. (PMID:15696470)
• may play a role in modifying the susceptibility to idiopathic spermatogenic impairment in human; allele A of c.216C>A seems to be a protective factor for the development of male infertility (PMID:17307919)
• clathrin-FKBP36-Hsp72 complexes resulting from both identified interactions are bound to the matrices of clathrin-coated vesicles in spermatocytes, which indicates a possible role of FKBP36 and Hsp72 in the disassembly of clathrin coats (PMID:18529014)
• FKBP36 diminishes GAPDH activity by direct interaction and down-regulation of GAPDH (PMID:19001379)
• Genome wide DNA methylation assessment approach identified novel biomarkers that differentiate between cervical cancer and normal samples. In the Validation cohort FKBP6 promoter methylation had 73% sensitivity and 80% specificity (AUC = 0.80). (PMID:24241165)
• The piRNA-pathway factor FKBP6 is essential for spermatogenesis but dispensable for control of meiotic LINE-1 expression in humans. (PMID:36150389)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	fkbp6	ENSDARG00000030133
		ENSDARG00000102022
mus_musculus	Fkbp6	ENSMUSG00000040013
rattus_norvegicus	Fkbp6	ENSRNOG00000001451
drosophila_melanogaster	shu	FBGN0003401
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430

Paralogs (18): FKBP4 (ENSG00000004478), FKBP7 (ENSG00000079150), FKBP1A (ENSG00000088832), FKBP5 (ENSG00000096060), FKBP3 (ENSG00000100442), FKBP8 (ENSG00000105701), FKBP14 (ENSG00000106080), FKBP15 (ENSG00000119321), FKBP1B (ENSG00000119782), FKBP9 (ENSG00000122642), TTC9 (ENSG00000133985), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Inactive peptidyl-prolyl cis-trans isomerase FKBP6 — O75344 (reviewed: O75344)

Alternative names: 36 kDa FK506-binding protein, FK506-binding protein 6, Immunophilin FKBP36

All UniProt accessions (5): O75344, A0A3B3IST2, C9JM01, F8WD36, F8WD38

UniProt curated annotations — full annotation on UniProt →

Function. Has an essential role in spermatogenesis. It is required to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes.

Subunit / interactions. Interacts (via TPR repeats) with HSP90. Interacts with HSP72/HSPA2 and CLTC. Interacts with GAPDH; leading to inhibit GAPDH catalytic activity.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Detected in all tissues examined, with higher expression in testis, heart, skeletal muscle, liver, and kidney.

Disease relevance. FKBP6 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of FKBP6 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. A father and son with Williams-Beuren syndrome appear to have a common heterozygous deletion that includes FKBP6 gene. However, the haploinsufficiency for FKBP6 does not appear to preclude male fertility. Spermatogenic failure 77 (SPGF77) [MIM:620103] An autosomal recessive male infertility disorder characterized by oligozoospermia or azoospermia, and abnormally shaped spermatozoa in the semen of affected individuals. Sperm abnormalities include double and triple tails, with amorphous or fragmented and enlarged heads, as well as pinhead sperm. Testicular tissue shows arrest at the round spermatid stage. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the FKBP6 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75344-1	1	yes
O75344-2	2
O75344-3	3

RefSeq proteins (4): NP_001128683, NP_001268233, NP_001349718, NP_003593* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001179	PPIase_FKBP_dom	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR042282	FKBP6/shu	Family
IPR046357	PPIase_dom_sf	Homologous_superfamily

Pfam: PF00254

UniProt features (25 total): strand 6, sequence conflict 3, helix 3, turn 3, repeat 3, sequence variant 3, splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3B7X	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75344-F1	91.11	0.80

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-5601884	PIWI-interacting RNA (piRNA) biogenesis

MSigDB gene sets: 545 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_MEIOTIC_SYNAPSIS, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_PROTEIN_MATURATION, MODULE_379, GOBP_VIRAL_GENOME_REPLICATION, GOBP_VIRAL_LIFE_CYCLE, GOBP_PROTEIN_FOLDING, GOBP_PIRNA_PROCESSING, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, chr7q11, MODULE_242

GO Biological Process (8): protein folding (GO:0006457), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), regulatory ncRNA-mediated gene silencing (GO:0031047), piRNA processing (GO:0034587), positive regulation of viral genome replication (GO:0045070), meiotic cell cycle (GO:0051321), transposable element silencing by piRNA-mediated DNA methylation (GO:0141196)

GO Molecular Function (6): FK506 binding (GO:0005528), identical protein binding (GO:0042802), Hsp90 protein binding (GO:0051879), peptidyl-prolyl cis-trans isomerase activity (GO:0003755), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (7): synaptonemal complex (GO:0000795), fibrillar center (GO:0001650), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), intercellular bridge (GO:0045171), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Meiosis	1
Gene Silencing by RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	1
protein maturation	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
negative regulation of gene expression	1
regulatory ncRNA processing	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
transposable element silencing by heterochromatin formation	1
gene silencing by piRNA-directed DNA methylation	1
macrolide binding	1
protein binding	1
heat shock protein binding	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
synaptonemal structure	1
nucleolus	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FKBP6	GTF2IRD1	Q9UHL9	836
FKBP6	PPIL4	Q8WUA2	826
FKBP6	TBL2	Q9Y4P3	798
FKBP6	FZD9	O00144	797
FKBP6	TRIM50	Q86XT4	778
FKBP6	PPIB	P23284	751
FKBP6	GTF2I	P78347	748
FKBP6	CLIP2	Q9UDT6	734
FKBP6	PPIF	P30405	731
FKBP6	BAZ1B	Q9UIG0	709
FKBP6	NSUN5	Q96P11	708
FKBP6	EIF4H	Q15056	670
FKBP6	LIMK1	P53667	643
FKBP6	BCL7B	Q9BQE9	626
FKBP6	ELN	P15502	614

IntAct

170 interactions, top by confidence:

A	B	Type	Score
CDK5RAP3	FKBP6	psi-mi:“MI:0915”(physical association)	0.860
FKBP6	CDK5RAP3	psi-mi:“MI:0915”(physical association)	0.860
FKBP6	IHO1	psi-mi:“MI:0915”(physical association)	0.830
IHO1	FKBP6	psi-mi:“MI:0915”(physical association)	0.830
LZTS2	FKBP6	psi-mi:“MI:0915”(physical association)	0.780
FKBP6	LZTS2	psi-mi:“MI:0915”(physical association)	0.780
SUMO1P1	FKBP6	psi-mi:“MI:0915”(physical association)	0.720
FKBP6	SUMO1P1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (137): CDK5RAP3 (Two-hybrid), LZTS2 (Two-hybrid), CCDC36 (Two-hybrid), SUMO1P1 (Two-hybrid), FKBP6 (Two-hybrid), FKBP6 (Affinity Capture-Western), FKBP6 (Biochemical Activity), IK (Affinity Capture-MS), HSP90AA5P (Affinity Capture-MS), CDC37L1 (Affinity Capture-MS), RGPD5 (Affinity Capture-MS), PPP1R12B (Affinity Capture-MS), PPP1R12A (Affinity Capture-MS), OSBP (Affinity Capture-MS), PRMT3 (Affinity Capture-MS)

ESM2 similar proteins: A2ADA5, A4PCD4, A6H611, D3ZDM7, F6PHZ6, O75344, P04053, P09838, P17256, P36195, P47823, P55345, Q01992, Q03426, Q08602, Q0V8R7, Q13144, Q1L8I0, Q3MIT2, Q4KM92, Q4QQT0, Q5CZL1, Q5E9Z1, Q5I0L3, Q5M7T9, Q5M934, Q5RFE6, Q5XGM5, Q64350, Q6GQ53, Q7L3T8, Q80W22, Q86YJ6, Q8BYL4, Q8C0D0, Q8CHW4, Q8N0Z8, Q8WWH5, Q91XW8, Q92089

Diamond homologs: A6QQ71, D3ZQF4, F6PHZ6, O42123, O42993, O46638, O54998, O75344, O94746, P0A0W2, P0A0W3, P0C1J3, P0C1J4, P0C1J5, P0C1J6, P0CP94, P0CP95, P0CP96, P0CP97, P18203, P20080, P20081, P26883, P26884, P26885, P27124, P28870, P30416, P30417, P32472, P44760, P45523, P45878, P48375, P54397, P56989, P57599, P62942, P62943, P65764

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	39
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1684032	NM_003602.5(FKBP6):c.589-2A>G	Pathogenic
1684033	NM_003602.5(FKBP6):c.508_529dup (p.Phe177fs)	Pathogenic
2574694	GRCh37/hg19 7q11.23(chr7:72664461-74162586)	Pathogenic
1683495	NM_003602.5(FKBP6):c.610C>T (p.Arg204Ter)	Likely pathogenic
1684034	NM_003602.5(FKBP6):c.832C>T (p.Arg278Ter)	Likely pathogenic
1684035	NM_003602.5(FKBP6):c.469-2A>T	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2109 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:73328637:G:C	K40N	0.995
7:73328637:G:T	K40N	0.995
7:73331721:G:A	G178D	0.995
7:73329398:T:C	F72L	0.994
7:73329400:C:A	F72L	0.994
7:73329400:C:G	F72L	0.994
7:73330206:G:C	A108P	0.994
7:73330282:T:A	V133D	0.994
7:73329372:G:A	G63E	0.992
7:73330213:T:C	F110S	0.991
7:73340723:T:C	L225P	0.991
7:73330164:G:C	G94R	0.990
7:73331712:G:C	R175P	0.990
7:73331757:C:A	A190D	0.990
7:73331756:G:C	A190P	0.989
7:73340828:G:A	G260E	0.989
7:73341273:G:C	A262P	0.989
7:73341324:G:C	A279P	0.989
7:73330180:T:A	L99H	0.988
7:73330287:T:C	F135L	0.988
7:73330289:T:A	F135L	0.988
7:73330289:T:G	F135L	0.988
7:73331721:G:T	G178V	0.988
7:73330165:G:A	G94D	0.987
7:73330176:G:C	G98R	0.987
7:73330234:C:A	A117D	0.987
7:73331720:G:C	G178R	0.987
7:73341325:C:A	A279D	0.987
7:73330180:T:C	L99P	0.986
7:73330285:T:C	L134P	0.986

dbSNP variants (sampled 300 via entrez): RS1000207035 (7:73339813 A>G), RS1000207468 (7:73351903 T>C), RS1000372015 (7:73333077 G>C), RS1000487636 (7:73353776 C>T), RS1000585122 (7:73348335 G>A,C), RS1000814370 (7:73341766 C>T), RS1000881856 (7:73340209 T>C), RS1000931893 (7:73341451 C>A,G), RS1001640889 (7:73348137 A>T), RS1001973024 (7:73349893 T>C), RS1002131335 (7:73356470 C>A,T), RS1002196053 (7:73354994 C>G), RS1002201960 (7:73343148 T>G), RS1002382971 (7:73335954 C>A,T), RS1002483867 (7:73356770 C>T)

Disease associations

OMIM: gene MIM:604839 | disease phenotypes: MIM:620103, MIM:609757

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 77	Strong	Autosomal recessive

Mondo (3): male infertility (MONDO:0005372), spermatogenic failure 77 (MONDO:0031083), 7q11.23 microduplication syndrome (MONDO:0012342)

Orphanet (1): 7q11.23 microduplication syndrome (Orphanet:96121)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
C565723	Williams-Beuren Region Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
testosterone undecanoate	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Levonorgestrel	affects cotreatment, increases expression	1
Particulate Matter	increases abundance, 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
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
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
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
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
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
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