HORMAD1

Summary

HORMAD1 (HORMA domain containing 1, HGNC:25245) is a protein-coding gene on chromosome 1q21.3, encoding HORMA domain-containing protein 1 (Q86X24). Plays a key role in meiotic progression.

This gene encodes a HORMA domain-containing protein. HORMA domains are involved in chromatin binding and play a role in cell cycle regulation. The encoded protein may play a role in meiosis, and expression of this gene is a potential marker for cancer. A pseudogene of this gene is located on the long arm of chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 84072 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 43 total — 1 pathogenic
• MANE Select transcript: NM_032132

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25245
Approved symbol	HORMAD1
Name	HORMA domain containing 1
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434A1315, CT46
Ensembl gene	ENSG00000143452
Ensembl biotype	protein_coding
OMIM	609824
Entrez	84072

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000322343, ENST00000361824, ENST00000368987, ENST00000368995, ENST00000442853, ENST00000470397, ENST00000476530, ENST00000486497

RefSeq mRNA: 2 — MANE Select: NM_032132 NM_001199829, NM_032132

CCDS: CCDS55633, CCDS967

Canonical transcript exons

ENST00000361824 — 15 exons

Exon	Start	End
ENSE00000960126	150708894	150708961
ENSE00000960127	150708256	150708407
ENSE00001044434	150711545	150711571
ENSE00001435820	150711833	150711853
ENSE00001435977	150714085	150714121
ENSE00001513340	150706553	150706809
ENSE00001864585	150698060	150698734
ENSE00003469401	150700112	150700183
ENSE00003534328	150704118	150704194
ENSE00003617345	150714615	150714678
ENSE00003622633	150719473	150719538
ENSE00003630193	150717138	150717282
ENSE00003632650	150703310	150703393
ENSE00003693924	150704277	150704343
ENSE00003844962	150720804	150720895

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 96.44.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3122 / max 228.7001, expressed in 7 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14344	0.2647	6
14343	0.0401	5
14342	0.0073	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	96.44	gold quality
right testis	UBERON:0004534	96.12	gold quality
left testis	UBERON:0004533	95.45	gold quality
testis	UBERON:0000473	93.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.32	gold quality
sperm	CL:0000019	90.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.15	gold quality
monocyte	CL:0000576	82.17	gold quality
leukocyte	CL:0000738	80.79	gold quality
granulocyte	CL:0000094	71.76	gold quality
skin of hip	UBERON:0001554	63.45	gold quality
esophagus mucosa	UBERON:0002469	63.41	gold quality
vermiform appendix	UBERON:0001154	63.26	gold quality
spleen	UBERON:0002106	62.24	gold quality
esophagus squamous epithelium	UBERON:0006920	61.91	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	61.49	gold quality
upper leg skin	UBERON:0004262	61.14	gold quality
rectum	UBERON:0001052	60.53	gold quality
skin of leg	UBERON:0001511	59.11	gold quality
tibial nerve	UBERON:0001323	59.02	gold quality
blood	UBERON:0000178	58.54	gold quality
caecum	UBERON:0001153	58.24	gold quality
lymph node	UBERON:0000029	57.82	gold quality
calcaneal tendon	UBERON:0003701	57.45	gold quality
zone of skin	UBERON:0000014	57.31	gold quality
skin of abdomen	UBERON:0001416	57.02	gold quality
gall bladder	UBERON:0002110	56.38	gold quality
right coronary artery	UBERON:0001625	56.27	gold quality
nasal cavity mucosa	UBERON:0001826	55.08	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	1190.68
E-CURD-11	yes	45.67
E-ANND-3	no	4.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting HORMAD1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-513C-5P	99.50	68.42	1730

Literature-anchored findings (GeneRIF, showing 13)

• This is the first report showing that HORMAD1 single-nucleotide polymorphisms (SNPs) may predispose men to a defect in spermatogenesis, although the causal and potential mechanistic relationships between these HORMAD1 SNPs and azoospermia remain unclear. (PMID:22407170)
• HORMAD1 gene silencing resulted in significantly reduced VEGF protein levels and microvessel density compared to controls in epithelial ovarian carcinoma. (PMID:22776561)
• Hormad1 and Hormad2 might not be the susceptible genes for the non-obstructive azoospermia in our study population. However, rs718772 of Hormad2 variant might be associated with testis development in NOA patients. (PMID:24803422)
• Genomic Complexity Profiling Reveals That HORMAD1 Overexpression Contributes to Homologous Recombination Deficiency in Triple-Negative Breast Cancers (PMID:25770156)
• Four sterility-related genes, including BOLL, DDX4, HORMAD1, and MAEL, were found to have increased methylation at CpGs of the promoter regions and decreased mRNA expressions in nonobstructive azoospermia and hypospermatogenesis (HS) testis and are believed to be associated with HS. (PMID:28342926)
• HORMAD1 expression specifies a novel subtype of lung adenocarcinoma, which has adapted to mitigate DNA damage (PMID:30185546)
• HORMAD1-dependent DSB repair as a new mechanism of radioresistance and a probable determinant of mutability in lung adenocarcinoma. (PMID:30333500)
• HORMAD1 promotes docetaxel resistance in triple negative breast cancer by enhancing DNA damage tolerance. (PMID:34036395)
• A biallelic loss of function variant in HORMAD1 within a large consanguineous Turkish family is associated with spermatogenic arrest. (PMID:36524333)
• Ectopically Expressed Meiosis-Specific Cancer Testis Antigen HORMAD1 Promotes Genomic Instability in Squamous Cell Carcinomas. (PMID:37371097)
• Structural and biochemical insights into the interaction mechanism underlying HORMAD1 and its partner proteins. (PMID:37794593)
• The cancer testes antigen, HORMAD1, limits genomic instability in cancer cells by protecting stalled replication forks. (PMID:37838177)
• Expression of HORMAD1 in Chronic Rhinosinusitis and Its Correlation with Inflammatory Factors. (PMID:38185961)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	hormad1	ENSDARG00000040254
mus_musculus	Hormad1	ENSMUSG00000028109
rattus_norvegicus	Hormad1	ENSRNOG00000021160
caenorhabditis_elegans		WBGENE00001862
caenorhabditis_elegans		WBGENE00002032
caenorhabditis_elegans		WBGENE00002033

Paralogs (1): HORMAD2 (ENSG00000176635)

Protein

Protein identifiers

HORMA domain-containing protein 1 — Q86X24 (reviewed: Q86X24)

Alternative names: Cancer/testis antigen 46, Newborn ovary HORMA protein

All UniProt accessions (4): Q86X24, A0A140VKG9, X6R751, X6RG95

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in meiotic progression. Regulates 3 different functions during meiosis: ensures that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends. Promotes synaptonemal-complex formation independently of its role in homology search. Plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes.

Subunit / interactions. Interacts with HORMAD2. Interacts with IHO1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Testis-specific. Over-expressed in carcinomas.

Post-translational modifications. Phosphorylated at Ser-377 in a SPO11-dependent manner.

Isoforms (5)

UniProt ID	Names	Canonical?
Q86X24-1	1, HORMAD1L	yes
Q86X24-2	2
Q86X24-3	3
Q86X24-4	4
Q86X24-5	5

RefSeq proteins (2): NP_001186758, NP_115508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003511	HORMA_dom	Domain
IPR036570	HORMA_dom_sf	Homologous_superfamily
IPR051294	HORMA_MeioticProgression	Family

Pfam: PF02301

UniProt features (35 total): strand 11, helix 6, compositionally biased region 5, splice variant 4, sequence conflict 3, chain 1, domain 1, sequence variant 1, region of interest 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J69	X-RAY DIFFRACTION	2.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86X24-F1	65.94	0.36

Functional residue map

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

Post-translational modifications (1): 376

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_OOGENESIS, GOBP_NEGATIVE_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_MALE_GAMETE_GENERATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, ATGTTAA_MIR302C, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (11): blastocyst development (GO:0001824), synaptonemal complex assembly (GO:0007130), spermatogenesis (GO:0007283), meiotic DNA double-strand break formation (GO:0042138), oogenesis (GO:0048477), meiotic sister chromatid cohesion (GO:0051177), meiotic cell cycle (GO:0051321), meiotic recombination checkpoint signaling (GO:0051598), regulation of homologous chromosome segregation (GO:0060629), homologous chromosome pairing at meiosis (GO:0007129), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): synaptonemal complex (GO:0000795), nucleus (GO:0005634), chromosome (GO:0005694), condensed nuclear chromosome (GO:0000794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromosome organization involved in meiotic cell cycle	2
homologous chromosome segregation	2
in utero embryonic development	1
anatomical structure development	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
synaptonemal complex organization	1
developmental process involved in reproduction	1
male gamete generation	1
DNA metabolic process	1
meiosis I cell cycle process	1
germ cell development	1
female gamete generation	1
sister chromatid cohesion	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
meiotic cell cycle checkpoint signaling	1
negative regulation of meiotic nuclear division	1
regulation of chromosome segregation	1
regulation of reproductive process	1
cellular developmental process	1
binding	1
synaptonemal structure	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
nuclear chromosome	1
condensed chromosome	1
nucleus	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HORMAD1	SYCP3	Q8IZU3	972
HORMAD1	IHO1	Q8IYA8	949
HORMAD1	MSH4	O15457	938
HORMAD1	SPO11	Q9Y5K1	897
HORMAD1	SYCP1	Q15431	868
HORMAD1	REC8	O95072	838
HORMAD1	SYCE1	Q8N0S2	833
HORMAD1	SYCE2	Q6PIF2	788
HORMAD1	MAD2L2	Q9UI95	782
HORMAD1	MSH5	O43196	770
HORMAD1	SYCP2	Q9BX26	754
HORMAD1	STAG3	Q9UJ98	751
HORMAD1	TEX12	Q9BXU0	749
HORMAD1	SMC3	Q9UQE7	737
HORMAD1	SYCE3	A1L190	732

IntAct

12 interactions, top by confidence:

A	B	Type	Score
HORMAD1	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	HORMAD1	psi-mi:“MI:0915”(physical association)	0.560
HORMAD1	MYG1	psi-mi:“MI:0915”(physical association)	0.560
MCM9	NOP56	psi-mi:“MI:0914”(association)	0.350
MCM9	PSMD14	psi-mi:“MI:0914”(association)	0.350
HORMAD1	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
HORMAD1	MYG1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): HORMAD1 (Two-hybrid), BRCA1 (Two-hybrid), HORMAD1 (Affinity Capture-MS), HORMAD1 (Affinity Capture-MS), HORMAD1 (Two-hybrid), HORMAD1 (Two-hybrid), HORMAD1 (Proximity Label-MS), HORMAD1 (Affinity Capture-MS), HORMAD1 (Affinity Capture-Western), FBXO47 (Affinity Capture-Western)

ESM2 similar proteins: A0A571BF63, A2BF66, A6QQY4, B0UYH6, D3ZWE7, E2QXH7, F6RRD7, O60566, O88665, P23611, P38531, Q05B18, Q08DB0, Q0P4I1, Q28IH8, Q2KIY6, Q3B7T8, Q3U1T9, Q3UB74, Q3YBR2, Q4R8B9, Q5HZK1, Q5I0E6, Q5JTW2, Q5M7C8, Q5PQK8, Q5PQQ9, Q5R789, Q5RA37, Q5SQP1, Q5XIZ9, Q66IH2, Q6IQY5, Q6NZY4, Q7T0S7, Q7Z3E5, Q86VD1, Q86X24, Q8BMD7, Q8C5W4

Diamond homologs: A2BF66, A6QQY4, D3ZWE7, E2IUK4, E2QXH7, E2RSQ2, F4HRV8, Q2KIY6, Q4R8B9, Q5M7C8, Q5SQP1, Q76CY8, Q86X24, Q8N7B1, Q9D5T7, F4JTJ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1711131	NM_032132.5(HORMAD1):c.1021C>T (p.Gln341Ter)	Pathogenic

SpliceAI

1775 predictions. Top by Δscore:

Variant	Effect	Δscore
1:150700187:C:CT	acceptor_gain	1.0000
1:150700187:C:T	acceptor_gain	1.0000
1:150703307:TACCA:T	donor_loss	1.0000
1:150703308:A:AC	donor_gain	1.0000
1:150703309:C:CC	donor_gain	1.0000
1:150703390:CAAC:C	acceptor_gain	1.0000
1:150703391:AAC:A	acceptor_gain	1.0000
1:150703393:CCTAA:C	acceptor_loss	1.0000
1:150703394:C:CC	acceptor_gain	1.0000
1:150704149:T:A	donor_gain	1.0000
1:150704195:C:CC	acceptor_gain	1.0000
1:150704271:TCTTA:T	donor_loss	1.0000
1:150704272:CTTAC:C	donor_loss	1.0000
1:150704273:TTA:T	donor_loss	1.0000
1:150704274:TAC:T	donor_loss	1.0000
1:150704276:C:A	donor_loss	1.0000
1:150704339:TCATC:T	acceptor_gain	1.0000
1:150704340:CATC:C	acceptor_gain	1.0000
1:150704340:CATCC:C	acceptor_gain	1.0000
1:150704352:T:C	acceptor_gain	1.0000
1:150704352:T:TC	acceptor_gain	1.0000
1:150704354:A:AC	acceptor_gain	1.0000
1:150704354:A:C	acceptor_gain	1.0000
1:150704356:G:GC	acceptor_gain	1.0000
1:150706548:CTTA:C	donor_loss	1.0000
1:150706550:TA:T	donor_loss	1.0000
1:150706551:A:AC	donor_gain	1.0000
1:150706552:C:CT	donor_gain	1.0000
1:150706552:CA:C	donor_gain	1.0000
1:150706552:CACT:C	donor_gain	1.0000

AlphaMissense

2631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:150706778:A:C	F193L	1.000
1:150706778:A:T	F193L	1.000
1:150706779:A:G	F193S	1.000
1:150706780:A:G	F193L	1.000
1:150717181:C:A	R45S	0.999
1:150717181:C:G	R45S	0.999
1:150717182:C:A	R45M	0.999
1:150717182:C:G	R45T	0.999
1:150708339:C:G	R155P	0.998
1:150708939:A:G	F117S	0.998
1:150711852:A:G	L94P	0.998
1:150717189:A:C	Y43D	0.998
1:150717201:A:G	S39P	0.998
1:150717218:A:G	L33P	0.998
1:150706780:A:C	F193V	0.997
1:150706788:G:T	P190H	0.997
1:150708273:A:G	L177P	0.997
1:150708946:A:C	Y115D	0.997
1:150714101:G:T	A88D	0.997
1:150714616:A:G	W81R	0.997
1:150714616:A:T	W81R	0.997
1:150706779:A:C	F193C	0.996
1:150706780:A:T	F193I	0.996
1:150708268:A:C	Y179D	0.996
1:150708273:A:T	L177H	0.996
1:150708345:A:G	L153P	0.996
1:150708353:G:C	S150R	0.996
1:150708353:G:T	S150R	0.996
1:150708355:T:G	S150R	0.996
1:150714111:A:G	C85R	0.996

dbSNP variants (sampled 300 via entrez): RS1000382411 (1:150699708 A>G,T), RS1000422517 (1:150716455 C>A), RS1000453790 (1:150716720 T>C), RS1000561264 (1:150709755 G>T), RS1000614525 (1:150701858 T>A,C), RS1000631431 (1:150699542 T>A), RS1000664094 (1:150722453 T>C,G), RS1000688179 (1:150702425 T>C), RS1000730860 (1:150714029 A>G), RS1000805721 (1:150720978 G>A), RS1000836865 (1:150721293 A>C), RS1001001993 (1:150699131 C>T), RS1001036680 (1:150709908 C>A,G,T), RS1001099714 (1:150713535 CA>C,CAA), RS1001344904 (1:150710467 A>G)

Disease associations

OMIM: gene MIM:609824 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive

Mondo (2): male infertility (MONDO:0005372), (MONDO:0018393)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001966_1	Rhegmatogenous retinal detachment	1.000000e-07
GCST004627_128	Lymphocyte count	3.000000e-10
GCST005951_38	Body mass index	4.000000e-09
GCST009597_133	Multiple sclerosis	6.000000e-08
GCST011124_1	Caffeine consumption from tea	6.000000e-10
GCST011125_1	Caffeine consumption from coffee	5.000000e-09
GCST011126_1	Caffeine consumption from coffee or tea	1.000000e-23
GCST011126_7	Caffeine consumption from coffee or tea	1.000000e-26
GCST90002388_625	Lymphocyte count	1.000000e-28
GCST90002399_6	Neutrophil percentage of white cells	9.000000e-18
GCST90020025_1214	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020027_1799	Waist-hip index	2.000000e-08
GCST90020028_622	Hip circumference adjusted for BMI	8.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0004340	body mass index
EFO:0010091	tea consumption measurement
EFO:0006781	coffee consumption measurement
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Decitabine	affects expression	1
Cisplatin	affects 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
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
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