USP31

protein-coding

ubiquitin specific peptidase 31, the group of Ubiquitin specific peptidases

Gene summary

Enables cysteine-type deubiquitinase activity. Predicted to be involved in protein deubiquitination and proteolysis. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_020718.4

Inheritance

—

ClinVar variants

U:230B:8

Top phenotype

Sensorineural hearing loss disorder

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr16:23,061,406-23,149,452

External References & Databases

Ensembl (ENSG00000103404)

Transcript & Mutation Effects

hg38 • Region Span ~88.0 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 USP31 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 218

not providedTotal: 3

Sensorineural hearing loss disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020718.4. 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			1 clinvar	2 clinvar		3
missense			221 clinvar	6 clinvar		227
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	230	8	0	238

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020718.4	RefSeq	NP_065769.3	16	MANE Select
ENST00000219689.12	Ensembl	ENSP00000219689.7	16	MANE Select
NM_001387221.1	RefSeq	NP_001374150.1	15	Standard
ENST00000563525.2	Ensembl	ENSP00000481339.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGFR1

Biological Process

ubiquitin-dependent protein catabolic process
protein deubiquitination

Molecular Function

thiol-dependent ubiquitin-specific protease activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219689
Coding exons: 16
Length: 87865
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	595	705	0.844	0.0000404	8697
Missense (PolyPhen)		210	318.9	0.65852		3799
Synonymous	-1.56	319	286	1.12	0.0000171	2796
Loss of Function	4.98	13	51.6	0.252	0.00000260	642

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May recognize and hydrolyze the peptide bond at the C- terminal Gly of ubiquitin. Involved in the processing of poly- ubiquitin precursors as well as that of ubiquitinated proteins (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.570
RVIS EVS: -0.06
RVIS percentile EVS: 48.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.945

Gene Damage Prediction

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