USP26

Summary

USP26 (ubiquitin specific peptidase 26, HGNC:13485) is a protein-coding gene on chromosome Xq26.2, encoding Ubiquitin carboxyl-terminal hydrolase 26 (Q9BXU7). Deubiquitinase regulating several biological processes through the deubiquitination of components of these processes.

This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases and is a deubiquitinating enzyme (DUB) with His and Cys domains. It is specifically expressed in testis tissue. Mutations in this gene have been associated with Sertoli cell-only syndrome and male infertility.

Source: NCBI Gene 83844 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure, X-linked, 6 (Limited, GenCC)
• Clinical variants (ClinVar): 105 total — 4 pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_031907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13485
Approved symbol	USP26
Name	ubiquitin specific peptidase 26
Location	Xq26.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134588
Ensembl biotype	protein_coding
OMIM	300309
Entrez	83844

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370832, ENST00000417459, ENST00000511190

RefSeq mRNA: 1 — MANE Select: NM_031907 NM_031907

CCDS: CCDS14635

Canonical transcript exons

ENST00000511190 — 6 exons

Exon	Start	End
ENSE00001700334	133083707	133083771
ENSE00001750297	133090113	133090226
ENSE00002025116	133091353	133091443
ENSE00002036822	133097030	133097109
ENSE00002065386	133090718	133090763
ENSE00002285397	133023168	133028296

Expression profiles

Bgee: expression breadth broad, 62 present calls, max score 79.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0183 / max 11.2837, expressed in 5 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200549	0.0183	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.53	gold quality
buccal mucosa cell	CL:0002336	58.52	gold quality
middle temporal gyrus	UBERON:0002771	49.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	48.03	gold quality
oocyte	CL:0000023	44.60	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
stromal cell of endometrium	CL:0002255	43.20	silver quality
secondary oocyte	CL:0000655	42.57	gold quality
cortical plate	UBERON:0005343	41.92	gold quality
heart right ventricle	UBERON:0002080	41.75	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
muscle tissue	UBERON:0002385	41.33	gold quality
colonic epithelium	UBERON:0000397	41.24	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
skeletal muscle tissue	UBERON:0001134	40.67	silver quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

Literature-anchored findings (GeneRIF, showing 28)

• Alterations in the USP26 gene may be involved in male infertility or might increase the risk of male infertility. These patients showed 370-371insACA, 494T>C and 1423C>T causing T123-124ins, L165S and H475Y, respectively (PMID:15562280)
• The USP26 gene may be of importance in male reproduction. Mutations in this gene may be associated with male infertility, and may negatively affect testicular function. (PMID:15970005)
• USP26 haplotype is present in significant frequencies in sub-Saharan African and South and East Asian populations, including in individuals with known fertility. This indicates that the allele is not associated with infertility. (PMID:16888075)
• Sequencing can confirm the presence of the three changes of the USP26 gene in patients of Caucasian origin with cryptozoospermia or oligozoospermia. (PMID:17121659)
• The USP26 gene might be of importance in male reproduction. Mutations in this gene might be associated with male infertility, and might negatively affect testicular function. (PMID:17968467)
• Mutations of the USP26 gene do not appear to be a common cause of idiopathic azoospermia or severe oligozoospermia. (PMID:18377898)
• Mutation within the USP26 gene is associated with risk of inguinal hernia leading to impaired male fertility. (PMID:18927127)
• Some USP26 alleles and haplotypes are associated with spermatogenic defect in the Han nationality in Taiwan (PMID:18958354)
• USP26 assembles with androgen receptors (AR)and other cofactors in subnuclear foci and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity. (PMID:20501646)
• results indicated the variation of USP26 was not directly associated with human sperm count but suggested it might be a potential role in sperm motility (PMID:21147082)
• The nucleotide polymorphisms of the Usp26 gene might be closely related with idiopathic male infertility, and exert a negative effect on the testis function. (PMID:22568204)
• there is a significant difference in USP26 gene expression between the obstructive azoospermia, complete maturation arrest samples and Sertoli Cell-Only Syndrome samples (PMID:23779098)
• There is an association of alteration in USP26 with male infertility, especially in azoospermia and in the Asian population. [Meta-Analysis] (PMID:24875820)
• Evidence from both enzymatic and meta-analyses does not support a direct association between USP26 variants and male infertility (PMID:25755145)
• A novel USP26 variant p.R344W is associated with nonobstructive azoospermia probably through affecting androgen receptor function. (PMID:27089915)
• identification in a normozoospermic man of a nonsense mutation (c.882C>A) which causes the production of a truncated protein, suggests a marginal role of USP26 in male spermatogenesis (PMID:27726449)
• The interaction between USP26 and Mdm2, and the subsequent deubiquitination of Mdm2, serves, most probably to regulate Mdm2. Future therapeutic modalities that interfere with the association between USP26 and Mdm2 will be used to destabilize the ligase in malignancies where it is upregulated. (PMID:27810359)
• findings demonstrate TGF-beta enhances expression of USP26 and reinforces SMAD7 stability by limiting the ubiquitin-mediated turnover of SMAD7; clinically, loss of USP26 correlates with high TGF-beta activity and confers poor prognosis in glioblastoma; data identify USP26 as a novel negative regulator of the TGF-beta pathway and suggest that loss of USP26 expression may be an important factor in glioblastoma pathogenesis (PMID:28381482)
• Data show that USP26 interacts with PRC1 components chromobox (CBX)-containing proteins CBX4 and CBX6. (PMID:28839133)
• These results represent the first in vivo evidence showing that USP26 is not essential for mouse gametogenesis. (PMID:30887115)
• Paternal USP26 mutations raise Klinefelter syndrome risk in the offspring of mice and humans. (PMID:33978233)
• Novel Mutations in X-Linked, USP26-Induced Asthenoteratozoospermia and Male Infertility. (PMID:34202084)
• The association between mutations in ubiquitin-specific protease 26 (USP26) and male infertility: a systematic review and meta-analysis. (PMID:35074940)
• USP26 promotes anaplastic thyroid cancer progression by stabilizing TAZ. (PMID:35397626)
• An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations. (PMID:35857630)
• Machine learning-based classification of deubiquitinase USP26 and its cell proliferation inhibition through stabilizing KLF6 in cervical cancer. (PMID:38064851)
• Acetylation-dependent deubiquitinase USP26 stabilizes BAG3 to promote breast cancer progression. (PMID:38880224)
• USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling. (PMID:39251623)

Cross-species orthologs

0 orthologs

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242), USP32 (ENSG00000170832)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 26 — Q9BXU7 (reviewed: Q9BXU7)

Alternative names: Deubiquitinating enzyme 26, Ubiquitin thioesterase 26, Ubiquitin-specific-processing protease 26

All UniProt accessions (1): Q9BXU7

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase regulating several biological processes through the deubiquitination of components of these processes. Involved in somatic cell reprogramming through the ‘Lys-48’-linked deubiquitination and stabilization of CBX4 and CBX6, two components of the polycomb-repressive complex 1 (PRC1). Also deubiquitinates and probably stabilizes the androgen receptor (AR), regulating the androgen receptor signaling pathway. May play a role in spermatogenesis.

Subunit / interactions. Interacts with RING1.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Expressed in testis.

Disease relevance. Spermatogenic failure, X-linked, 6 (SPGFX6) [MIM:301101] A male infertility disorder due to asthenoteratozoospermia and characterized by reduced progressive sperm motility and morphologic sperm abnormalities, such as thin heads and short or coiled flagella. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase C19 family.

RefSeq proteins (1): NP_114113* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR032069	USP37-like_PH	Domain
IPR038093	USP37-like_PH_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443, PF16674

UniProt features (16 total): sequence variant 8, region of interest 2, active site 2, chain 1, domain 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXU7-F1	60.28	0.28

Functional residue map

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

Catalytic / active sites (2): 304 (nucleophile); 841 (proton acceptor)

Mutagenesis-validated functional residues (1):

Position	Phenotype
304	loss of deubiquitinase activity. decreased regulation of androgen receptor signaling pathway.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 132 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GOBP_MALE_GAMETE_GENERATION, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY

GO Biological Process (7): G1/S transition of mitotic cell cycle (GO:0000082), proteolysis (GO:0006508), spermatogenesis (GO:0007283), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), regulation of androgen receptor signaling pathway (GO:0060765)

GO Molecular Function (7): cysteine-type deubiquitinase activity (GO:0004843), deubiquitinase activity (GO:0101005), K48-linked deubiquitinase activity (GO:1990380), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
deubiquitinase activity	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
protein metabolic process	1
developmental process involved in reproduction	1
male gamete generation	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
androgen receptor signaling pathway	1
regulation of intracellular steroid hormone receptor signaling pathway	1
cysteine-type peptidase activity	1
ubiquitin-like protein peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
9+2 motile cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

951 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP26	ZUP1	Q96AP4	603
USP26	USP44	Q9H0E7	542
USP26	USP14	P54578	539
USP26	OTUB1	Q96FW1	530
USP26	USP1	O94782	525
USP26	USP7	Q93009	520
USP26	USP17L2	Q6R6M4	519
USP26	PAN2	Q504Q3	512
USP26	USP5	P45974	507
USP26	JOSD1	Q15040	506
USP26	OTUD6A	Q7L8S5	503
USP26	UCHL5	Q9Y5K5	501
USP26	TNP2	Q05952	495
USP26	TNP1	P09430	490
USP26	USP49	Q70CQ1	490

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CFTR	USP26	psi-mi:“MI:0915”(physical association)	0.510
USP26	AK2	psi-mi:“MI:0915”(physical association)	0.400
USP17L7	USP26	psi-mi:“MI:0915”(physical association)	0.400
CDKN2A	ACTN4	psi-mi:“MI:0914”(association)	0.350

BioGRID (250): AR (Affinity Capture-Western), USP26 (Affinity Capture-Western), MDM2 (Affinity Capture-Western), ZEB1 (Affinity Capture-Western), USP26 (Affinity Capture-Western), Ring1 (Affinity Capture-Western), Pcgf2 (Affinity Capture-Western), Cbx6 (Affinity Capture-Western), Cbx4 (Affinity Capture-Western), CBX6 (Affinity Capture-Western), CBX4 (Affinity Capture-Western), Cbx7 (Affinity Capture-Western), USP26 (PCA), USP26 (Affinity Capture-Western), USP26 (PCA)

ESM2 similar proteins: A1Z1Q3, A6H8Y1, A7MBJ2, B2RX14, B8QB46, D3ZF42, F6QRE9, O02751, O70551, O94972, P17029, P23497, Q08995, Q08AY6, Q0V9E9, Q13342, Q3UVR3, Q3UZ39, Q498E6, Q587J6, Q588U8, Q5BLK4, Q5DTT8, Q5RD27, Q5RE50, Q5RHP9, Q5T7B8, Q5T7N2, Q5TAX3, Q5VYS8, Q61687, Q63HK3, Q6IQ55, Q6PCX9, Q7Z5L2, Q8BJM3, Q8BUH8, Q8IW19, Q8L7S0, Q92834

Diamond homologs: A0JM59, A5PMR2, A5PN09, A6H8I0, A6NNY8, A6QNM7, A7Z056, A8MUK1, B1AY13, B1WBD7, C9J2P7, C9JJH3, C9JLJ4, C9JPN9, C9JVI0, D3ZJ96, D6R901, D6R9N7, D6RA61, D6RBM5, D6RBQ6, D6RCP7, D6RJB6, E1C213, E2RK09, E7F6T8, F1N5V1, F1SRY5, F6Z5C0, F8VPZ3, M9PD06, O00507, O60079, O74442, O94966, O96612, P0C7I0, P0C8Z3, P35125, P39538

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	69
Likely benign	24
Benign	7

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
147683	GRCh38/hg38 Xp22.33-q28(chrX:2782275-155611794)x2	Pathogenic
2444461	NM_031907.3(USP26):c.2473C>G (p.Arg825Gly)	Pathogenic
2444462	NM_031907.3(USP26):c.2396A>G (p.Asn799Ser)	Pathogenic
2507003	NM_031907.3(USP26):c.1205A>C (p.Asn402Thr)	Pathogenic

SpliceAI

50 predictions. Top by Δscore:

Variant	Effect	Δscore
X:133028067:G:C	donor_gain	0.9900
X:133028066:AG:A	donor_gain	0.9800
X:133028101:CA:C	donor_gain	0.8700
X:133028043:C:CT	donor_gain	0.8600
X:133028044:T:TT	donor_gain	0.8600
X:133028066:A:AC	donor_gain	0.7600
X:133028059:A:AC	donor_gain	0.7500
X:133028066:AGC:A	donor_gain	0.7000
X:133028102:AG:A	donor_gain	0.5900
X:133028086:T:A	donor_gain	0.5300
X:133026566:T:TC	acceptor_gain	0.5100
X:133028129:T:A	donor_gain	0.3900
X:133027888:T:TA	donor_gain	0.3800
X:133027878:C:A	donor_gain	0.3700
X:133028087:C:CT	donor_gain	0.3600
X:133027424:A:AC	donor_gain	0.3500
X:133028121:T:TA	donor_gain	0.3500
X:133025570:A:C	acceptor_gain	0.3400
X:133028085:TTCC:T	donor_gain	0.3400
X:133027429:CAA:C	donor_gain	0.3300
X:133027430:AAA:A	donor_gain	0.3300
X:133027431:AAA:A	donor_gain	0.3300
X:133027876:ACC:A	donor_gain	0.3300
X:133027877:CCC:C	donor_gain	0.3300
X:133028247:ATCT:A	donor_gain	0.3300
X:133027885:A:T	donor_gain	0.3200
X:133027428:CCA:C	donor_gain	0.3100
X:133028103:GC:G	donor_gain	0.3100
X:133026759:C:CT	acceptor_gain	0.3000
X:133028114:T:C	donor_gain	0.3000

AlphaMissense

6084 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:133025661:A:G	W854R	0.989
X:133025661:A:T	W854R	0.989
X:133025747:C:G	R825P	0.974
X:133025737:A:C	S828R	0.973
X:133025737:A:T	S828R	0.973
X:133025739:T:G	S828R	0.973
X:133025728:G:C	S831R	0.972
X:133025728:G:T	S831R	0.972
X:133025730:T:G	S831R	0.972
X:133026680:G:T	P514H	0.972
X:133025574:A:C	Y883D	0.971
X:133025751:A:C	Y824D	0.971
X:133026680:G:C	P514R	0.969
X:133026910:A:C	N437K	0.969
X:133026910:A:T	N437K	0.969
X:133025659:C:A	W854C	0.964
X:133025659:C:G	W854C	0.964
X:133027283:A:G	L313P	0.963
X:133025589:C:A	G878W	0.962
X:133026665:A:T	V519D	0.960
X:133027096:G:C	F375L	0.960
X:133027096:G:T	F375L	0.960
X:133027098:A:G	F375L	0.960
X:133027063:A:C	F386L	0.959
X:133027063:A:T	F386L	0.959
X:133027065:A:G	F386L	0.959
X:133025685:C:G	A846P	0.957
X:133026671:A:G	L517P	0.957
X:133026676:T:A	R515S	0.955
X:133026676:T:G	R515S	0.955

dbSNP variants (sampled 300 via entrez): RS1000004255 (X:133096416 C>G,T), RS1000026481 (X:133082336 C>T), RS1000051639 (X:133045848 A>C), RS1000080052 (X:133063970 G>A), RS1000168974 (X:133081550 C>A,T), RS1000199615 (X:133082039 C>T), RS1000306878 (X:133071215 C>A,G), RS1000308121 (X:133030797 G>A), RS1000315586 (X:133082742 C>G), RS1000333304 (X:133039893 C>T), RS1000398436 (X:133060495 G>A), RS1000403596 (X:133091298 T>C), RS1000501117 (X:133051053 A>G), RS1000617229 (X:133050535 A>T), RS1000679198 (X:133061934 A>G)

Disease associations

OMIM: gene MIM:300309 | disease phenotypes: MIM:301101

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure, X-linked, 6	Limited	Unknown

Mondo (3): spermatogenic failure, X-linked, 6 (MONDO:0859478), male infertility (MONDO:0005372), oligospermia (MONDO:0001913)

Orphanet (0):

HPO phenotypes

13 total (14 of 13 shown, HPO-id order):

HPO	Term
HP:0000032	Abnormal male external genitalia morphology
HP:0000403	Recurrent otitis media
HP:0001417	X-linked inheritance
HP:0002837	Recurrent bronchitis
HP:0003251	Male infertility
HP:0006532	Recurrent pneumonia
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0032561	Microcephalic sperm head
HP:0033525	Absent sperm axoneme central pair complex
HP:0034011	Reduced progressive sperm motility
HP:0000798	Oligozoospermia

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
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

149 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
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT05320536	PHASE4	UNKNOWN	A Clinical Study of Gulingji Capsule in the Treatment of Idiopathic Oligospermia, Asthenia, and Teratozoospermia
NCT06260007	PHASE4	RECRUITING	Efficacy and Safety Study of Products Based on Tribulus Terrestris, L. in Men With Oligospermia
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
NCT00440180	PHASE3	TERMINATED	Aromatase Inhibitors in the Treatment of Male Infertility
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
NCT01409837	PHASE2	COMPLETED	The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
NCT02234206	PHASE2	COMPLETED	A Clinical Trial to Study the Safety and Efficacy of Chandrakanthi Choornam in Patients With Low Sperm Count
NCT07481370	PHASE2	ENROLLING_BY_INVITATION	Isotretinoin vs hCG for Male Infertility Due to Low or Absent Sperm
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
NCT05158114	PHASE1	WITHDRAWN	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Testicular Injury and Oligospermia
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