USP27X

ubiquitin specific peptidase 27 X-linked, the group of Ubiquitin specific peptidases

Basic information

Region (hg38): X:49879484-49882558

Links

ENSG00000273820 ∙ NCBI:389856 ∙ OMIM:300975 ∙ HGNC:13486 ∙ Uniprot:A6NNY8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: XLR
• intellectual disability, X-linked 105 (Strong), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: XL
• X-linked intellectual disability (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 105	XL	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	Neurologic	25644381

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the USP27X gene.

• Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the USP27X 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				6	2	8
missense		1	20	1	1	23
nonsense		2				2
start loss						0
frameshift	1	3	1			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	6	22	7	3

Variants in USP27X

This is a list of pathogenic ClinVar variants found in the USP27X region.

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

Position	Type	Phenotype	Significance	ClinVar
X-49880229-G-C			Uncertain significance (-)
X-49880345-A-G		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
X-49880365-G-C		Inborn genetic diseases	Uncertain significance (Jun 10, 2022)
X-49880366-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 01, 2024)
X-49880396-C-T		not specified	Uncertain significance (Jan 15, 2024)
X-49880401-G-A		Intellectual disability, X-linked 105	Uncertain significance (Dec 16, 2019)
X-49880413-C-T		Neurodevelopmental disorder • Intellectual disability, X-linked 105	Pathogenic/Likely pathogenic (Aug 31, 2021)
X-49880417-A-G		Inborn genetic diseases	Uncertain significance (Dec 30, 2022)
X-49880426-T-C		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
X-49880445-A-T			Uncertain significance (Aug 01, 2024)
X-49880468-A-C		not specified	Uncertain significance (Sep 30, 2015)
X-49880515-A-G			Likely benign (May 01, 2024)
X-49880528-CGATC-AGA			Likely pathogenic (Feb 12, 2022)
X-49880529-G-A			Likely benign (Jan 01, 2021)
X-49880533-G-A		Intellectual disability, X-linked 105	Uncertain significance (-)
X-49880595-C-T			Likely benign (Dec 31, 2019)
X-49880612-TGA-T		Intellectual disability	Pathogenic (Feb 13, 2019)
X-49880699-G-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
X-49880701-G-T		Intellectual disability, X-linked 105	Likely pathogenic (-)
X-49880738-A-G		Intellectual disability, X-linked 105	Uncertain significance (-)
X-49880778-A-G			Likely benign (Dec 31, 2019)
X-49880816-T-C		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
X-49880848-A-G		Intellectual disability, X-linked 105	Uncertain significance (-)
X-49880913-C-G		Inborn genetic diseases	Uncertain significance (Oct 27, 2023)
X-49880970-C-T			Likely benign (Jul 01, 2022)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinase that can reduce the levels of BCL2L11/BIM ubiquitination and stabilize BCL2L11 in response to the RAF-MAPK- degradation signal. By acting on BCL2L11 levels, may counteract the anti-apoptotic effects of MAPK activity. {ECO:0000250|UniProtKB:Q8CEG8}.
• Disease: DISEASE: Mental retardation, X-linked 105 (MRX105) [MIM:300984]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. {ECO:0000269|PubMed:25644381}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.110

Haploinsufficiency Scores

• pHI: 0.446
• hipred: N
• hipred_score: 0.368

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Usp27x

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein deubiquitination;positive regulation of apoptotic process;protein stabilization;protein K63-linked deubiquitination;protein K48-linked deubiquitination
• Cellular component: nucleus;cytosol
• Molecular function: thiol-dependent ubiquitin-specific protease activity;Lys63-specific deubiquitinase activity;Lys48-specific deubiquitinase activity