USP26

protein-coding

ubiquitin specific peptidase 26, the group of Ubiquitin specific peptidases

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_031907.3

Inheritance

ClinVar variants

P:3U:69B:30

Top phenotype

Spermatogenic failure, X-linked, 6

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chrX:133,023,168-133,097,109

External References & Databases

Ensembl (ENSG00000134588)

Transcript & Mutation Effects

hg38 • Region Span ~73.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure, X-linked, 6LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859478

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spermatogenic failure, X-linked, 6XL

Manifestation: Genitourinary

Intervention: General

Rationale: 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

Refs: 36796361

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to USP26 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 75

not providedTotal: 19

USP26-related disorderTotal: 11

Spermatogenic failure, X-linked, 6Total: 3

Abnormal sperm morphologyTotal: 1

Male infertilityTotal: 1

Reduced sperm motilityTotal: 1

OligospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031907.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				9 clinvar	2 clinvar	11
missense	3 clinvar		67 clinvar	16 clinvar	3 clinvar	89
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	3	0	69	25	5	102

Highest pathogenic variant AF is 0.000004553564

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031907.3	RefSeq	NP_114113.1	1	MANE Select
ENST00000511190.6	Ensembl	ENSP00000423390.1	1	MANE Select
ENST00000370832.1	Ensembl	ENSP00000359869.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Ub-specific processing proteases
Deubiquitination

Biological Process

G1/S transition of mitotic cell cycle
ubiquitin-dependent protein catabolic process
protein deubiquitination

Molecular Function

cysteine-type endopeptidase activity
thiol-dependent ubiquitin-specific protease activity
protein binding
thiol-dependent ubiquitinyl hydrolase activity

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000511190
Coding exons: 1
Length: 72479

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0837	321	317	1.01	0.0000224	6067
Missense (PolyPhen)		44	67.513	0.65172		1490
Synonymous	-0.300	126	122	1.03	0.00000885	1681
Loss of Function

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the ubiquitin-dependent proteolytic pathway in conjunction with the 26S proteasome (By similarity). Deubiquitinates the androgen receptor and regulates the androgen receptor signaling pathway. {ECO:0000250, ECO:0000269|PubMed:20501646}.;

Recessive Scores

pRec: 0.0741

Intolerance Scores

LoFtool: 0.414
RVIS EVS: 0.46
RVIS percentile EVS: 78.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.161

Gene Damage Prediction

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