USP9Y

ubiquitin specific peptidase 9 Y-linked, the group of Armadillo like helical domain containing|Minor histocompatibility antigens|Ubiquitin specific peptidases

Basic information

Region (hg38): Y:12537650-12860839

Links

ENSG00000114374 ∙ NCBI:8287 ∙ OMIM:400005 ∙ HGNC:12633 ∙ Uniprot:O00507 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure, Y-linked, 2	YL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary	9384609; 10402373; 10507722; 10581029; 10767340; 16893908; 18205040; 19246359

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP9Y gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP9Y gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	1	4
missense			5	1		6
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding						0
Total	0	0	6	4	1

Variants in USP9Y

This is a list of pathogenic ClinVar variants found in the USP9Y region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
Y-12735724-TTAAG-T		Spermatogenic failure, Y-linked, 2	Pathogenic (Dec 01, 1999)
Y-12739592-C-G		USP9Y-related disorder	Likely benign (Aug 09, 2019)
Y-12778040-C-T			Likely benign (Aug 01, 2022)
Y-12786501-CTT-C		USP9Y-related disorder	Likely benign (Aug 09, 2019)
Y-12786672-C-T			Uncertain significance (Dec 01, 2023)
Y-12793053-C-G		Spermatogenic failure, Y-linked, 2	Uncertain significance (Jan 22, 2021)
Y-12810225-A-C			Likely benign (Nov 01, 2022)
Y-12812934-C-T			Benign (Nov 12, 2018)
Y-12818466-T-C			Uncertain significance (Mar 01, 2023)
Y-12833864-A-G			Uncertain significance (Oct 01, 2023)
Y-12839999-G-T			Uncertain significance (Nov 01, 2022)
Y-12840450-C-T		Spermatogenic failure, Y-linked, 2	Uncertain significance (Apr 04, 2021)
Y-12842370-G-T		Spermatogenic failure, Y-linked, 2	Uncertain significance (Nov 02, 2023)
Y-12842411-C-T			Likely benign (Mar 01, 2023)
Y-12843101-G-A			Uncertain significance (Jan 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
USP9Y	protein_coding	protein_coding	ENST00000338981	44	159605

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000574	1.00	67925	25	0	67950	0.000184

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.391	409	387	1.06	0.0000595	16977
Missense in Polyphen		129	131.11	0.98388		5686
Synonymous	-1.35	148	129	1.15	0.0000193	4700
Loss of Function	3.52	14	37.2	0.377	0.00000626	1628

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00179	0.00107
Ashkenazi Jewish	0.00116	0.000579
East Asian	0.000443	0.000221
Finnish	0.000178	0.0000887
European (Non-Finnish)	0.000288	0.000142
Middle Eastern	0.000443	0.000221
South Asian	0.000190	0.0000867
Other	0.000665	0.000312

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a ubiquitin-protein or polyubiquitin hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin. Essential component of TGF-beta/BMP signaling cascade. Deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33. Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiquitination of SMAD4 by USP9X re-empowers its competence to mediate TGF-beta signaling (By similarity). {ECO:0000250}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10581029}. Note=The disease may be caused by mutations affecting the gene represented in this entry. The role of USP9Y in spermatogenesis failure is uncertain (PubMed:19246359). A 4-bp deletion in a splice-donor site, causing exon skipping and protein truncation has been observed in non- obstructive azoospermia (PubMed:10581029). However, complete USP9Y deletion has been detected in individuals with no spermatogenic defects (PubMed:19246359). {ECO:0000269|PubMed:10581029, ECO:0000269|PubMed:19246359}.

Haploinsufficiency Scores

• pHI: 0.330
• hipred: N
• hipred_score: 0.422
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.167

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Usp9y

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;transforming growth factor beta receptor signaling pathway;spermatogenesis;protein deubiquitination;BMP signaling pathway
• Cellular component: cytoplasm
• Molecular function: cysteine-type endopeptidase activity;thiol-dependent ubiquitin-specific protease activity;cysteine-type peptidase activity;co-SMAD binding