USP17L24

Summary

USP17L24 (ubiquitin specific peptidase 17 like family member 24, HGNC:44453) is a protein-coding gene on chromosome 4p16.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 24 (Q0WX57). 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.

Enables RNA binding activity; cysteine-type deubiquitinase activity; and hyaluronic acid binding activity. Involved in positive regulation of epithelial cell apoptotic process and protein deubiquitination involved in ubiquitin-dependent protein catabolic process. Located in nucleolus.

Source: NCBI Gene 728369 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001242327

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44453
Approved symbol	USP17L24
Name	ubiquitin specific peptidase 17 like family member 24
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000232264
Ensembl biotype	protein_coding
Entrez	728369

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000504481

RefSeq mRNA: 7 — MANE Select: NM_001242327 NM_001242327, NM_001421913, NM_001421916, NM_001421920, NM_001421921, NM_001421923, NM_001421928

CCDS: CCDS59464

Canonical transcript exons

ENST00000504481 — 1 exons

Exon	Start	End
ENSE00002030897	9325165	9326757

Expression profiles

Bgee: expression breadth not_expressed, 0 present calls, max score 39.86.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	39.86	gold quality
bone marrow cell	CL:0002092	37.92	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ganglionic eminence	UBERON:0004023	37.12	gold quality
lower esophagus mucosa	UBERON:0035834	36.70	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
skeletal muscle tissue	UBERON:0001134	34.68	gold quality
bone marrow	UBERON:0002371	33.68	gold quality
superior frontal gyrus	UBERON:0002661	32.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	32.02	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
primary visual cortex	UBERON:0002436	30.12	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.78	gold quality
urinary bladder	UBERON:0001255	29.68	gold quality
monocyte	CL:0000576	28.67	gold quality
tonsil	UBERON:0002372	28.63	gold quality
leukocyte	CL:0000738	28.57	gold quality
liver	UBERON:0002107	28.50	gold quality
calcaneal tendon	UBERON:0003701	28.15	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
blood	UBERON:0000178	26.52	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
kidney	UBERON:0002113	25.99	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
frontal cortex	UBERON:0001870	25.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

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 24 — Q0WX57 (reviewed: Q0WX57)

Alternative names: Deubiquitinating enzyme 17, Ubiquitin thioesterase 17, Ubiquitin-specific-processing protease 17

All UniProt accessions (1): Q0WX57

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. Nucleolus. Endoplasmic reticulum.

Tissue specificity. Expressed in heart, brain, liver and skeletal muscle.

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

RefSeq proteins (7): NP_001229256, NP_001408842, NP_001408845, NP_001408849, NP_001408850, NP_001408852, NP_001408857 (=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 (23 total): sequence conflict 12, compositionally biased region 4, region of interest 2, active site 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0WX57-F1	67.66	0.46

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): 89 (nucleophile); 334 (proton acceptor)

Mutagenesis-validated functional residues (1):

Position	Phenotype
89	abolishes enzymatic activity. loss of the pro-apoptotic function.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 38 (showing top): GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GERY_CEBP_TARGETS, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, chr4p16, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_PROTEIN_CATABOLIC_PROCESS

GO Biological Process (7): apoptotic process (GO:0006915), regulation of protein stability (GO:0031647), regulation of apoptotic process (GO:0042981), protein deubiquitination involved in ubiquitin-dependent protein catabolic process (GO:0071947), positive regulation of epithelial cell apoptotic process (GO:1904037), proteolysis (GO:0006508), protein deubiquitination (GO:0016579)

GO Molecular Function (6): RNA binding (GO:0003723), cysteine-type deubiquitinase activity (GO:0004843), hyaluronic acid binding (GO:0005540), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleolus (GO:0005730), 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
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of biological quality	1
apoptotic process	1
regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
protein deubiquitination	1
positive regulation of apoptotic process	1
epithelial cell apoptotic process	1
regulation of epithelial cell apoptotic process	1
protein metabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
nucleic acid binding	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
carboxylic acid binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
nuclear lumen	1
intracellular membraneless organelle	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L24	RCE1	Q9Y256	603
USP17L24	ZUP1	Q96AP4	593
USP17L24	OTUD5	Q96G74	532
USP17L24	USP25	Q9UHP3	519
USP17L24	USP13	Q92995	489
USP17L24	SUDS3	Q9H7L9	473
USP17L24	CYLD	Q9NQC7	467
USP17L24	USP5	P45974	463
USP17L24	OTUD6B	Q8N6M0	463
USP17L24	USP28	Q96RU2	444
USP17L24	FAM90A10	A6NDY2	435
USP17L24	JOSD1	Q15040	426
USP17L24	OTUD7B	Q6GQQ9	420
USP17L24	OTUD1	Q5VV17	412
USP17L24	UCHL3	P15374	406

IntAct

4 interactions, top by confidence:

A	B	Type	Score
USP17L24	USP17L7	psi-mi:“MI:0914”(association)	0.350
USP17L2	USP17L7	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (9): USP17L24 (Affinity Capture-MS), USP17L27 (Negative Genetic), USP17L28 (Negative Genetic), USP17L29 (Negative Genetic), USP17L27 (Negative Genetic), USP17L29 (Negative Genetic), USP17L24 (Affinity Capture-MS), USP17L24 (Affinity Capture-MS), USP17L24 (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	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062783	GRCh37/hg19 4p16.3-15.31(chr4:68345-19103550)x1	Pathogenic

SpliceAI

64 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9326455:G:GT	donor_gain	0.5300
4:9325279:G:GC	acceptor_gain	0.4900
4:9326456:A:T	donor_gain	0.4900
4:9326438:TGGA:T	donor_gain	0.4800
4:9326529:CGAAG:C	donor_loss	0.4500
4:9326530:GAAGG:G	donor_loss	0.4500
4:9326531:AAGG:A	donor_loss	0.4500
4:9326532:AGGT:A	donor_loss	0.4500
4:9326533:GGTAC:G	donor_loss	0.4500
4:9326534:GTA:G	donor_loss	0.4500
4:9326535:T:G	donor_loss	0.4500
4:9326528:TCGAA:T	donor_loss	0.4200
4:9326536:A:C	donor_loss	0.4200
4:9326382:A:T	donor_gain	0.4000
4:9326528:TCGA:T	donor_gain	0.3900
4:9326263:GCC:G	donor_gain	0.3800
4:9325432:T:TA	acceptor_gain	0.3700
4:9325433:A:AA	acceptor_gain	0.3700
4:9326282:T:G	acceptor_gain	0.3500
4:9325941:G:C	acceptor_gain	0.3300
4:9326439:GGAA:G	donor_gain	0.3300
4:9325372:C:CG	donor_gain	0.3200
4:9326441:A:T	donor_gain	0.3200
4:9326502:G:GT	donor_gain	0.3200
4:9325278:TG:T	acceptor_gain	0.3100
4:9326368:C:T	donor_gain	0.3100
4:9325372:C:G	donor_gain	0.3000
4:9326281:A:AG	acceptor_gain	0.2900
4:9326285:A:AG	acceptor_gain	0.2900
4:9326286:G:GG	acceptor_gain	0.2900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS111262992 (4:9324320 C>T), RS111375616 (4:9326638 T>A), RS112333446 (4:9326109 C>T), RS113901365 (4:9326710 A>C), RS113970271 (4:9325066 C>A,T), RS1156416862 (4:9325373 T>A), RS1158682797 (4:9324725 C>A), RS1158738010 (4:9324300 T>C), RS1158747506 (4:9324662 C>A,T), RS1161241746 (4:9324178 T>A,G), RS1163139710 (4:9324156 C>A,T), RS1166550894 (4:9324172 GT>G), RS11730859 (4:9324639 G>A,T), RS1174233460 (4:9324781 T>A), RS1175352958 (4:9325439 AC>A)

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: yes

ChEMBL targets (1): CHEMBL4523281 (SINGLE PROTEIN)

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
Cadmium	decreases expression, increases abundance	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4372597	Binding	Inhibition of USP17 in HEK293T cell lysates at 25 uM using HA-tagged vinyl-sulfone as substrate preincubated for 19 to 60 mins followed by substrate addition and measured after 19 to 25 mins by Western blot analysis	Diarylcarbonates are a new class of deubiquitinating enzyme inhibitor. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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