USP35

protein-coding

ubiquitin specific peptidase 35, the group of Ubiquitin specific peptidases

Gene summary

This gene encodes a member of the peptidase C19 family of ubiquitin-specific proteases. These deubiquitinating enzymes (DUBs) catalyze the removal of ubiquitin proteins from other proteins. The encoded protein associates with polarized mitochondria and has been shown to inhibit NF-kappa B activation and delay PARK2-mediated degradation of mitochondria. Expression of this gene is upregulated by the let-7a microRNA and reduced expression has been observed in human tumor tissues. [provided by RefSeq, Jul 2017]

MANE transcript

NM_020798.4

Inheritance

—

ClinVar variants

U:203B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr11:78,188,812-78,215,232

External References & Databases

Ensembl (ENSG00000118369)

Transcript & Mutation Effects

hg38 • Region Span ~26.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to USP35 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 198

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020798.4. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			199 clinvar	6 clinvar		205
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	203	7	1	211

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020798.4	RefSeq	NP_065849.1	10	MANE Select
ENST00000529308.6	Ensembl	ENSP00000431876.1	10	MANE Select
ENST00000526425.1	Ensembl	ENSP00000434942.1	8	Standard
ENST00000526425.2	Ensembl	ENSP00000434942.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent protein catabolic process
protein deubiquitination

Molecular Function

cysteine-type endopeptidase activity
thiol-dependent ubiquitin-specific protease activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000529308
Coding exons: 10
Length: 25900
Individuals with no LoFs: 124853
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 124919
p: 0.000264

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.294	589	569	1.03	0.0000376	6469
Missense (PolyPhen)		124	118.97	1.0423		1254
Synonymous	-1.36	280	253	1.11	0.0000173	2139
Loss of Function	2.81	16	33.6	0.477	0.00000143	429

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000064	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00028	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00032	0.00030	rare
South Asian	0.00013	0.00013	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.760
RVIS EVS: 2.05
RVIS percentile EVS: 97.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0955

Gene Damage Prediction

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