USP9Y

Summary

USP9Y (ubiquitin specific peptidase 9 Y-linked, HGNC:12633) is a protein-coding gene on chromosome Yq11.221, encoding Ubiquitin carboxyl-terminal hydrolase 9Y (O00507). Deubiquitinase that mediates deubiquitination of target proteins.

This gene is a member of the peptidase C19 family. It encodes a protein that is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins.

Source: NCBI Gene 8287 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 182 total — 2 pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_004654

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12633
Approved symbol	USP9Y
Name	ubiquitin specific peptidase 9 Y-linked
Location	Yq11.221
Locus type	gene with protein product
Status	Approved
Aliases	DFFRY, FAF-Y, AZFA
Ensembl gene	ENSG00000114374
Ensembl biotype	protein_coding
OMIM	400005
Entrez	8287

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000338981, ENST00000417071, ENST00000426564, ENST00000440408, ENST00000453031, ENST00000457658, ENST00000471409, ENST00000493168, ENST00000651177, ENST00000857541, ENST00000932610, ENST00000932611, ENST00000932612, ENST00000932613, ENST00000932614, ENST00000932615, ENST00000942408

RefSeq mRNA: 1 — MANE Select: NM_004654 NM_004654

CCDS: CCDS14781

Canonical transcript exons

ENST00000338981 — 46 exons

Exon	Start	End
ENSE00001020125	12708634	12708693
ENSE00001020131	12701231	12702055
ENSE00001601104	12842240	12842465
ENSE00003467347	12725113	12725225
ENSE00003476240	12846933	12847153
ENSE00003476271	12720589	12720737
ENSE00003476364	12778019	12778259
ENSE00003487242	12738157	12738309
ENSE00003502466	12859279	12860839
ENSE00003508322	12790407	12790532
ENSE00003510955	12778606	12778755
ENSE00003513236	12847239	12847327
ENSE00003515132	12771068	12771155
ENSE00003547650	12793032	12793201
ENSE00003548868	12841010	12841133
ENSE00003550081	12735998	12736249
ENSE00003552773	12839864	12840614
ENSE00003555621	12775471	12775566
ENSE00003557039	12760484	12760617
ENSE00003560948	12786203	12786333
ENSE00003561084	12786522	12786800
ENSE00003564733	12812830	12813052
ENSE00003566318	12758506	12758642
ENSE00003585886	12833688	12833861
ENSE00003586868	12843064	12843193
ENSE00003595540	12857566	12857661
ENSE00003601630	12739525	12739629
ENSE00003602419	12722108	12722187
ENSE00003621719	12773583	12773925
ENSE00003621863	12779526	12779646
ENSE00003624888	12736411	12736549
ENSE00003635310	12837911	12838052
ENSE00003651478	12709388	12709543
ENSE00003652645	12811635	12811781
ENSE00003654441	12856340	12856496
ENSE00003654508	12735612	12735727
ENSE00003655936	12776649	12776860
ENSE00003664000	12791499	12791624
ENSE00003666147	12757192	12757398
ENSE00003669946	12818420	12818610
ENSE00003679141	12810672	12810818
ENSE00003681535	12816124	12816344
ENSE00003686311	12846333	12846518
ENSE00003686907	12856633	12856845
ENSE00003693194	12726575	12726793
ENSE00003694071	12810179	12810287

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 90.43.

FANTOM5 (CAGE): breadth broad, TPM avg 10.7775 / max 979.4527, expressed in 882 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201153	10.7775	882
201155	0.7355	357
201158	0.7290	293
201157	0.5250	271
201154	0.3297	190
201156	0.2703	115
201151	0.0647	25

Top tissues by expression

288 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	90.43	gold quality
right lung	UBERON:0002167	89.53	gold quality
metanephros cortex	UBERON:0010533	89.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.82	gold quality
prostate gland	UBERON:0002367	87.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.19	gold quality
upper leg skin	UBERON:0004262	87.17	gold quality
seminal vesicle	UBERON:0000998	86.94	gold quality
apex of heart	UBERON:0002098	86.64	gold quality
corpus epididymis	UBERON:0004359	86.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.57	gold quality
cerebellar vermis	UBERON:0004720	85.05	gold quality
caput epididymis	UBERON:0004358	84.25	gold quality
adenohypophysis	UBERON:0002196	84.00	gold quality
cauda epididymis	UBERON:0004360	83.67	gold quality
adrenal tissue	UBERON:0018303	83.37	gold quality
cerebellar hemisphere	UBERON:0002245	83.18	gold quality
right adrenal gland	UBERON:0001233	82.98	gold quality
cerebellar cortex	UBERON:0002129	82.95	gold quality
right adrenal gland cortex	UBERON:0035827	82.54	gold quality
cartilage tissue	UBERON:0002418	82.44	gold quality
rectum	UBERON:0001052	82.24	gold quality
upper lobe of left lung	UBERON:0008952	81.70	gold quality
ventricular zone	UBERON:0003053	81.53	gold quality
cortical plate	UBERON:0005343	81.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.33	gold quality
parietal pleura	UBERON:0002400	81.32	gold quality
cerebellum	UBERON:0002037	81.31	gold quality
right testis	UBERON:0004534	81.27	gold quality
testis	UBERON:0000473	80.92	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.09
E-HCAD-25	no	623.28
E-ENAD-27	no	316.85
E-MTAB-7606	no	177.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting USP9Y, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814

Literature-anchored findings (GeneRIF, showing 30)

• detection of mrna in azooermic men (PMID:11869379)
• results suggest that, through de-ubiquitination, ubiquitin specific protease 9(USP9Y) may stabilize a specific target protein that is important for male germ cell development (PMID:12895410)
• Selection is acting to maintain the amino acid sequence of both the X and the Y-linked genes. (PMID:12925892)
• Findings indicated that AZF microdeletion and chromosomal abnormality should be important causes of male infertility. (PMID:15696490)
• rare Y chromosome missense mutation in exon 25 of human USP9Y revealed by pyrosequencing (PMID:18205040)
• Frequency of AZF microdeletions in peripheral leukocytes and testicular cells in Chinese men with idiopathic infertility. (PMID:18357961)
• Both the b2/b3 partial deletion and the DAZ3/4+CDY1a deletion pattern were associated with spermatogenic failure. (PMID:19088127)
• partial AZFc deletions might not play a role in predisposing genetic background for the phenotype of azoospermic Klinefelter syndrome subjects. (PMID:19909597)
• there could be an association between the AZFc region and Klinefelter syndrome (PMID:20603808)
• analysis of the loss of the AZFc region due to a human Y-chromosome microdeletion in infertile male patients (PMID:20603812)
• A comprehensive analysis of AZF structure and gene content was undertaken. (PMID:20671934)
• High prevalence of AZFb microdeletion in Iranian patients with idiopathic non-obstructive azoospermia. (PMID:20847372)
• results from genetic screening in the Netherlands: identification of partial AZF deletions in c region resulting from non-homologous recombination; one deletion, the P3c deletion, seems to be associated with increased sperm count (PMID:21227940)
• percentage of microdeletions in the AZF region is low in Slovak azoospermic patients, but important from a prognostic view. (PMID:21475375)
• Deletion of sY255 and sY254 as well as sY157 is the most common pattern of AZFc microdeletion in the Chinese Han population. (PMID:21837945)
• The microdeletion of AZFb+c+d was one of the important causes of the high level of FSH. (PMID:21983735)
• genetic association studies: Data from 4 unrelated azoospermic patients in France with Y chromosome deletions exclude HSFY1/HSF2 genes as factors in AZFb/P4 palindrome haplogroup required for spermatogenesis. (PMID:22158087)
• An impact of the identified polymorphism on discrimination of alleles of the M46 locus with various techniques was discussed, and solutions ensuring correctness of the genotyping results were proposed. (PMID:23650841)
• male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in the Chinese-Yi population (PMID:24009201)
• AZFd deletions were found to be significant (P < 0.05) in male infertility and it may be associated with other types of AZF deletions. (PMID:24528375)
• genetic association study in population in China: Data suggest b2/b3 partial deletions (both deletion-only and deletion-duplication) in AZFc (azoospermia factor c region) are associated with infertility due to spermatogenic impairment (azoospermia). (PMID:24935076)
• This is the first research investigating the utility of TTTY15-USP9Y in prostate cancer detection (PMID:26008593)
• We investigated partial deletion of AZFc region and DAZ copy number in a population of Iranian infertile men and normozoospermic controls. Partial AZFc deletions were not significantly different between the infertile and normozoospermic men. (PMID:27739146)
• AZF gene microdeletions in azoospermic-oligozoospermic males. (PMID:35999075)
• Y-chromosome haplogroups and Azoospermia Factor (AZF) analysis in Tunisian infertile male. (PMID:36591797)
• DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia. (PMID:36997603)
• High incidence of AZF duplications in clan-structured Iranian populations detected through Y chromosome sequencing read depth analysis. (PMID:37481605)
• [Analysis of copy number variation in AZF region of Y chromosome in patients with spermatogenic failure]. (PMID:37643951)
• AZF microdeletion affects semen parameters, sex hormone levels, and chromosome karyotypes in infertile men in Xinjiang. (PMID:38158680)
• Antioncogenic roles of USP9Y and DDX3Y in lung cancer: USP9Y stabilizes DDX3Y by preventing its degradation through deubiquitination. (PMID:38217953)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp9	ENSDARG00000013708
mus_musculus	Usp9y	ENSMUSG00000069044
rattus_norvegicus	Usp9y	ENSRNOG00000058664

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), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), 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 9Y — O00507 (reviewed: O00507)

Alternative names: Deubiquitinating enzyme FAF-Y, Fat facets protein-related, Y-linked, Ubiquitin thioesterase FAF-Y, Ubiquitin-specific protease 9, Y chromosome, Ubiquitin-specific-processing protease FAF-Y

All UniProt accessions (2): O00507, H7C2M9

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase that mediates deubiquitination of target proteins. May stabilize target proteins that are important for male germ cell development.

Tissue specificity. Widely expressed in embryonic and adult tissues.

Disease relevance. USP9Y is located in the ‘azoospermia factor a’ (AZFa) region on chromosome Y which is deleted in Sertoli cell-only syndrome. This is an infertility disorder in which no germ cells are visible in seminiferous tubules leading to azoospermia. However, AZFa deletions resulting in complete loss of USP9Y have also been found in normospermic men. Spermatogenic failure Y-linked 2 (SPGFY2) [MIM:415000] A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility. The disease may be caused by variants affecting the gene represented in this entry. The role of USP9Y in spermatogenesis failure is uncertain. A 4-bp deletion in a splice-donor site, causing exon skipping and protein truncation has been observed in non-obstructive azoospermia. However, complete USP9Y deletion has been detected in individuals with no spermatogenic defects.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the peptidase C19 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00507-1	Long	yes
O00507-2	Short

RefSeq proteins (1): NP_004645* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018200	USP_CS	Conserved_site
IPR021905	DUF3517	Domain
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family
IPR055176	UBP24/USP9X/USP9Y_UBL	Domain
IPR056850	ARM_UBP34_24_USP9X_Y	Domain

Pfam: PF00443, PF12030, PF22900, PF25010

UniProt features (44 total): sequence conflict 17, modified residue 5, sequence variant 5, compositionally biased region 5, binding site 4, region of interest 3, active site 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00507-F1	79.64	0.32

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): 1568 (nucleophile); 1881 (proton acceptor)

Ligand- & substrate-binding residues (4): 1729; 1731; 1773; 1776

Post-translational modifications (5): 589, 591, 2444, 2541, 2548

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 118 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_RESPONSE_TO_BMP, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_TRANSFORMING_GROWTH_FACTOR_BETA_RECEPTOR_SIGNALING_PATHWAY, GOMF_SMAD_BINDING, RUNNE_GENDER_EFFECT_UP, GOBP_PROTEOLYSIS

GO Biological Process (7): proteolysis (GO:0006508), transforming growth factor beta receptor signaling pathway (GO:0007179), spermatogenesis (GO:0007283), cell migration (GO:0016477), protein deubiquitination (GO:0016579), BMP signaling pathway (GO:0030509), regulation of protein stability (GO:0031647)

GO Molecular Function (6): cysteine-type deubiquitinase activity (GO:0004843), cysteine-type peptidase activity (GO:0008234), metal ion binding (GO:0046872), co-SMAD binding (GO:0070410), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transforming growth factor beta receptor superfamily signaling pathway	2
cellular anatomical structure	2
protein metabolic process	1
cellular response to transforming growth factor beta stimulus	1
developmental process involved in reproduction	1
male gamete generation	1
cell motility	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
cellular response to BMP stimulus	1
regulation of biological quality	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
peptidase activity	1
cation binding	1
SMAD binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

858 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP9Y	DDX3Y	O15523	985
USP9Y	UTY	O14607	983
USP9Y	KDM5D	Q9BY66	978
USP9Y	TMSB4Y	O14604	903
USP9Y	RBMY1A1	P0DJD3	884
USP9Y	DAZ1	Q9NQZ3	879
USP9Y	EIF1AY	O14602	877
USP9Y	ZFY	P08048	876
USP9Y	BPY2	O14599	821
USP9Y	RPS4Y1	P22090	801
USP9Y	CDY1	Q9Y6F8	789
USP9Y	PRY	O14603	780
USP9Y	DAZ2	Q13117	758
USP9Y	NLGN4Y	Q8NFZ3	734
USP9Y	RBMY1D	P0C7P1	727

IntAct

37 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
SHC1	BCR/ABL fusion	psi-mi:“MI:0914”(association)	0.460
USP9Y	RPS6	psi-mi:“MI:0915”(physical association)	0.400
SIRT1	KPNA3	psi-mi:“MI:0915”(physical association)	0.400
CFAP96	USP9Y	psi-mi:“MI:0915”(physical association)	0.400
Hsph1	USP9Y	psi-mi:“MI:0914”(association)	0.350
ORF21	USP9Y	psi-mi:“MI:0914”(association)	0.350
AKT2	USP9Y	psi-mi:“MI:0914”(association)	0.350
CLK3	USP9Y	psi-mi:“MI:0914”(association)	0.350
HS2ST1	USP9Y	psi-mi:“MI:0914”(association)	0.350
NCKIPSD	USP9Y	psi-mi:“MI:0914”(association)	0.350
MAP2K3	SUPT5H	psi-mi:“MI:0914”(association)	0.350
PRKD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
MAP2K3	USP9Y	psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350
TESK2	ILVBL	psi-mi:“MI:0914”(association)	0.350
KANSL3	POTEF	psi-mi:“MI:0914”(association)	0.350
SOCS1	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
CCL16	USP9Y	psi-mi:“MI:0914”(association)	0.350
RAMAC	USP9Y	psi-mi:“MI:0914”(association)	0.350
CCDC9	USP9Y	psi-mi:“MI:0914”(association)	0.350
DDHD1	USP9Y	psi-mi:“MI:0914”(association)	0.350
VCPIP1	USP9Y	psi-mi:“MI:0914”(association)	0.350
KIAA0408	USP9Y	psi-mi:“MI:0914”(association)	0.350
LINC02912	USP9Y	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): USP9Y (Affinity Capture-MS), USP9Y (Synthetic Lethality), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS), USP9Y (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: A0A0R4IB93, A0JM59, A5PMR2, A5PN09, A6NNY8, A6QNM7, A7Z056, B1AY13, B1WBD7, D2HBJ8, D6RBM5, E1C213, E7F6T8, E9Q9U0, F6Z5C0, F8VPU6, F8VPZ3, M9PD06, O00507, O22207, O60079, O74442, O94269, O94966, O96612, P0C7I0, P0C8Z3, P0CAQ1, P35125, P39538, P40453, P51784, P53874, P55824, P70398, Q01988, Q09738, Q0V9G5, Q28CN3, Q2HJE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	15
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
9757	NM_004654.4(USP9Y):c.773+3_773+6del	Pathogenic
9758	USP9Y, DEL	Pathogenic

SpliceAI

7977 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:12709539:ACCAG:A	donor_loss	1.0000
Y:12709540:CCAG:C	donor_loss	1.0000
Y:12709541:CAGG:C	donor_loss	1.0000
Y:12709542:AGGTA:A	donor_loss	1.0000
Y:12709544:GT:G	donor_loss	1.0000
Y:12709545:T:G	donor_loss	1.0000
Y:12720582:A:AG	acceptor_gain	1.0000
Y:12720587:A:G	acceptor_gain	1.0000
Y:12722096:A:AG	acceptor_gain	1.0000
Y:12722183:AAAAG:A	donor_loss	1.0000
Y:12722186:AGG:A	donor_loss	1.0000
Y:12722188:GTGA:G	donor_loss	1.0000
Y:12722189:T:A	donor_loss	1.0000
Y:12725109:TTA:T	acceptor_loss	1.0000
Y:12725110:TA:T	acceptor_loss	1.0000
Y:12725111:A:AG	acceptor_gain	1.0000
Y:12725111:AGGC:A	acceptor_loss	1.0000
Y:12725112:G:A	acceptor_loss	1.0000
Y:12725112:G:GG	acceptor_gain	1.0000
Y:12725226:G:GG	donor_gain	1.0000
Y:12726794:G:GG	donor_gain	1.0000
Y:12731182:G:GT	donor_gain	1.0000
Y:12735610:AG:A	acceptor_gain	1.0000
Y:12735611:GG:G	acceptor_gain	1.0000
Y:12735724:TTAAG:T	donor_loss	1.0000
Y:12735725:TAAGT:T	donor_loss	1.0000
Y:12735726:AAGT:A	donor_loss	1.0000
Y:12735727:AGTA:A	donor_loss	1.0000
Y:12735728:G:GG	donor_gain	1.0000
Y:12735729:T:A	donor_loss	1.0000

AlphaMissense

16990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:12833726:A:C	D1687A	1.000
Y:12833726:A:T	D1687V	1.000
Y:12839930:T:C	F1802L	1.000
Y:12839932:T:A	F1802L	1.000
Y:12839932:T:G	F1802L	1.000
Y:12840143:C:G	H1873D	1.000
Y:12847143:T:C	L2322P	1.000
Y:12847308:G:C	D2349H	1.000
Y:12847309:A:T	D2349V	1.000
Y:12856340:A:C	R2355S	1.000
Y:12856340:A:T	R2355S	1.000
Y:12856431:T:G	Y2386D	1.000
Y:12856657:T:A	W2416R	1.000
Y:12856657:T:C	W2416R	1.000
Y:12856675:T:A	W2422R	1.000
Y:12856675:T:C	W2422R	1.000
Y:12856677:G:C	W2422C	1.000
Y:12856677:G:T	W2422C	1.000
Y:12856679:T:C	L2423P	1.000
Y:12856802:C:A	A2464D	1.000
Y:12856823:C:A	A2471D	1.000
Y:12725208:T:A	W141R	0.999
Y:12725208:T:C	W141R	0.999
Y:12725210:G:C	W141C	0.999
Y:12725210:G:T	W141C	0.999
Y:12736430:T:C	F349L	0.999
Y:12736432:T:A	F349L	0.999
Y:12736432:T:G	F349L	0.999
Y:12816196:T:C	L1561P	0.999
Y:12816216:T:C	C1568R	0.999

dbSNP variants (sampled 300 via entrez): RS1000027311 (Y:12828351 A>G), RS1000123202 (Y:12829839 A>G), RS1000218384 (Y:12728425 G>A), RS1000303388 (Y:12762331 T>C), RS1000637563 (Y:12769878 C>T), RS1000755616 (Y:12736617 T>C), RS1000819678 (Y:12727094 C>T), RS1000952990 (Y:12737870 A>C), RS1001160495 (Y:12718890 T>G), RS1001400672 (Y:12717332 C>T), RS1001456003 (Y:12846132 C>T), RS1001590232 (Y:12848499 T>C), RS1001792048 (Y:12756101 T>C), RS1002189867 (Y:12789493 G>T), RS1002210328 (Y:12753855 T>A)

Disease associations

OMIM: gene MIM:400005 | disease phenotypes: MIM:415000

GenCC curated gene-disease

Mondo (1): spermatogenic failure, Y-linked, 2 (MONDO:0010767)

Orphanet (1): Chromosome Y microdeletion syndrome (Orphanet:1646)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000798	Oligozoospermia
HP:0001450	Y-linked inheritance
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564030	Spermatogenic Failure, Nonobstructive, Y-Linked (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
Benzo(a)pyrene	decreases expression	2
arsenite	decreases methylation, increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
incobotulinumtoxinA	decreases expression	1
Caffeine	increases phosphorylation	1
Chromium	decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	decreases reaction, decreases expression	1
Vanadates	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases expression, increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D6SS	WAe001-A-2F	Embryonic stem cell	Male

Clinical trials (associated diseases)

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