USP17L10

Summary

USP17L10 (ubiquitin specific peptidase 17 like family member 10, HGNC:44438) is a protein-coding gene on chromosome 4p16.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 10 (C9JJH3). Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes that may include cell proliferation, progression through the cell cycle, apoptosis, cell migration, and the cellular response to viral infection. It is a selective cancer dependency (DepMap: 10.0% of cell lines).

Predicted to enable cysteine-type deubiquitinase activity. Predicted to be involved in regulation of apoptotic process and regulation of protein stability. Predicted to be located in endoplasmic reticulum. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 100287144 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• Cancer dependency (DepMap): dependent in 10.0% of screened cell lines
• MANE Select transcript: NM_001256852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44438
Approved symbol	USP17L10
Name	ubiquitin specific peptidase 17 like family member 10
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000231396
Ensembl biotype	protein_coding
Entrez	100287144

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000417945

RefSeq mRNA: 1 — MANE Select: NM_001256852 NM_001256852

CCDS: CCDS59454

Canonical transcript exons

ENST00000417945 — 1 exons

Exon	Start	End
ENSE00001750330	9210657	9212249

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 37.20.

Top tissues by expression

131 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ganglionic eminence	UBERON:0004023	37.12	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
tonsil	UBERON:0002372	28.52	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
blood	UBERON:0000178	25.94	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
leukocyte	CL:0000738	25.37	gold quality
monocyte	CL:0000576	25.15	gold quality
muscle of leg	UBERON:0001383	24.85	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
frontal cortex	UBERON:0001870	24.01	gold quality
pancreas	UBERON:0001264	23.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.08

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.0% of screened cell lines.

Cross-species orthologs

0 orthologs

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 17-like protein 10 — C9JJH3 (reviewed: C9JJH3)

All UniProt accessions (1): C9JJH3

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes that may include cell proliferation, progression through the cell cycle, apoptosis, cell migration, and the cellular response to viral infection.

Subcellular location. Nucleus. Endoplasmic reticulum.

Similarity. Belongs to the peptidase C19 family. USP17 subfamily.

RefSeq proteins (1): NP_001243781* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443

UniProt features (11 total): compositionally biased region 5, active site 2, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9JJH3-F1	67.01	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 334 (proton acceptor); 89 (nucleophile)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases

MSigDB gene sets: 14 (showing top): GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, chr4p16, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_PEPTIDASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, REACTOME_DEUBIQUITINATION, REACTOME_UB_SPECIFIC_PROCESSING_PROTEASES, GOBP_REGULATION_OF_PROGRAMMED_CELL_DEATH, GOBP_PROTEIN_MODIFICATION_PROCESS, GOMF_DEUBIQUITINASE_ACTIVITY

GO Biological Process (4): proteolysis (GO:0006508), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), regulation of apoptotic process (GO:0042981)

GO Molecular Function (4): cysteine-type deubiquitinase activity (GO:0004843), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Deubiquitination	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cytoplasm	2
protein metabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
apoptotic process	1
regulation of programmed cell death	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

76 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L10	NUP37	Q8NFH4	399
USP17L10	LAMTOR1	Q6IAA8	324
USP17L10	MACROH2A1	O75367	303
USP17L10	SEPTIN9	Q9UHD8	252
USP17L10	RPRD1B	Q9NQG5	222
USP17L10	COQ9	O75208	185
USP17L10	NDUFB10	O96000	174
USP17L10	MCM2	P49736	167
USP17L10	ATP5ME	P56385	167
USP17L10	UQCRB	P14927	167
USP17L10	NDUFB5	O43674	166
USP17L10	TWF1	Q12792	160
USP17L10	DCTN2	Q13561	157
USP17L10	ATP5PD	O75947	147
USP17L10	NOP2	P46087	146

IntAct

2 interactions, top by confidence:

A	B	Type	Score
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (3): USP17L29 (Negative Genetic), USP17L10 (Affinity Capture-MS), USP17L10 (Affinity Capture-MS)

ESM2 similar proteins: A2A5N8, A6NCW0, A6NCW7, A8MUK1, B1AQJ2, B2RQC2, C9J2P7, C9JJH3, C9JLJ4, C9JPN9, C9JVI0, D3ZWK4, D6R901, D6R9N7, D6RA61, D6RBM5, D6RBQ6, D6RCP7, D6RJB6, E9Q9U0, G5E8G2, G5E8I7, O94966, P0C7H9, P0C7I0, P35125, P51784, Q0E2F9, Q0WX57, Q2TAC6, Q3UJD6, Q4KLL9, Q5R7G8, Q5TKR9, Q61068, Q66HE5, Q6J1Y9, Q6PFD6, Q6QN14, Q6R6M4

Diamond homologs: A1L1K8, A6NCW0, A6NCW7, A8MUK1, C9J2P7, C9JJH3, C9JLJ4, C9JPN9, C9JVI0, D6R901, D6R9N7, D6RA61, D6RBQ6, D6RCP7, D6RJB6, G1SW77, P0C7H9, P0C7I0, Q0WX57, Q5JVS0, Q5XJA5, Q6AXS5, Q6NRY1, Q6PB22, Q6R6M4, Q7RTZ2, Q8NC51, Q9CY58, Q9I9R0, Q9JKS5, A0JM59, A5PMR2, A5PN09, A6H8I0, A6NNY8, A6QNM7, A7Z056, B1AY13, B1WBD7, D3ZJ96

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

57 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9211948:A:T	donor_gain	0.6300
4:9212021:CGAAG:C	donor_loss	0.6000
4:9212023:AAGG:A	donor_loss	0.6000
4:9212024:AG:A	donor_loss	0.6000
4:9212025:GGT:G	donor_loss	0.6000
4:9212026:GTAC:G	donor_loss	0.6000
4:9212027:T:G	donor_loss	0.5900
4:9210771:G:GC	acceptor_gain	0.5500
4:9211947:G:GT	donor_gain	0.5400
4:9210770:TGAGA:T	acceptor_gain	0.4900
4:9212022:GAAG:G	donor_gain	0.4900
4:9210770:TG:T	acceptor_gain	0.4700
4:9210770:T:TA	acceptor_gain	0.4600
4:9211930:TGGA:T	donor_gain	0.4400
4:9212026:G:GG	donor_gain	0.4400
4:9211755:GCC:G	donor_gain	0.4100
4:9212128:CGACG:C	acceptor_gain	0.3700
4:9212020:TCGAA:T	donor_loss	0.3500
4:9212028:A:C	donor_loss	0.3500
4:9212129:GACGA:G	acceptor_gain	0.3500
4:9211433:G:C	acceptor_gain	0.3300
4:9211774:T:G	acceptor_gain	0.3200
4:9211773:A:AG	acceptor_gain	0.3000
4:9211860:C:T	donor_gain	0.3000
4:9211874:A:T	donor_gain	0.3000
4:9212071:A:G	acceptor_gain	0.3000
4:9212127:TCGAC:T	acceptor_gain	0.3000
4:9211777:A:AG	acceptor_gain	0.2800
4:9211778:G:GG	acceptor_gain	0.2800
4:9211778:GAAGA:G	acceptor_gain	0.2800

AlphaMissense

3497 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:9211503:T:C	F283L	0.904
4:9211505:C:A	F283L	0.904
4:9211505:C:G	F283L	0.904
4:9211146:T:C	F164L	0.901
4:9211148:T:A	F164L	0.901
4:9211148:T:G	F164L	0.901
4:9211418:T:G	C254W	0.892
4:9211417:G:A	C254Y	0.891
4:9211416:T:A	C254S	0.884
4:9211417:G:C	C254S	0.884
4:9211113:T:C	F153L	0.873
4:9211115:C:A	F153L	0.873
4:9211115:C:G	F153L	0.873
4:9211425:T:C	C257R	0.873
4:9211427:T:G	C257W	0.873
4:9211416:T:C	C254R	0.871
4:9211425:T:A	C257S	0.865
4:9211426:G:C	C257S	0.865
4:9211417:G:T	C254F	0.842
4:9211426:G:A	C257Y	0.837
4:9211692:T:A	W346R	0.837
4:9211692:T:C	W346R	0.837
4:9211767:T:C	F371L	0.837
4:9211769:T:A	F371L	0.837
4:9211769:T:G	F371L	0.837
4:9211245:T:C	F197L	0.819
4:9211247:T:A	F197L	0.819
4:9211247:T:G	F197L	0.819
4:9211155:T:C	F167L	0.813
4:9211157:C:A	F167L	0.813

dbSNP variants (sampled 300 via entrez): RS1051690168 (4:9209893 A>G), RS1157038845 (4:9211961 C>A), RS1157285748 (4:9210927 G>A), RS1157491888 (4:9209338 C>A,G), RS1157644284 (4:9210607 G>C,T), RS1158782506 (4:9211695 T>A,G), RS1158816961 (4:9211117 A>G), RS1160644305 (4:9211124 C>A), RS1160739567 (4:9212492 T>A), RS1161032231 (4:9211351 G>GCTGTCTC), RS1161254663 (4:9210920 C>A,T), RS1161368102 (4:9208677 C>A), RS1161470519 (4:9212677 G>A,C), RS1161920816 (4:9212365 A>G), RS1162024719 (4:9210648 C>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
2-palmitoylglycerol	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.