USP17L12

Summary

USP17L12 (ubiquitin specific peptidase 17 like family member 12, HGNC:44440) is a protein-coding gene on chromosome 4p16.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 12 (C9JPN9). 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.

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 100287205 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001256853

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44440
Approved symbol	USP17L12
Name	ubiquitin specific peptidase 17 like family member 12
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000227551
Ensembl biotype	protein_coding
Entrez	100287205

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000415041

RefSeq mRNA: 1 — MANE Select: NM_001256853 NM_001256853

CCDS: CCDS59456

Canonical transcript exons

ENST00000415041 — 1 exons

Exon	Start	End
ENSE00001680713	9220152	9221744

Expression profiles

Bgee: expression breadth not_expressed, 0 present calls, max score 38.28.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	38.28	gold 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	UBERON:0002371	33.86	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	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	29.19	gold quality
liver	UBERON:0002107	28.80	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.88	gold quality
urinary bladder	UBERON:0001255	26.65	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.16	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
muscle of leg	UBERON:0001383	25.52	gold quality
leukocyte	CL:0000738	24.80	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
pancreas	UBERON:0001264	24.58	gold quality
kidney	UBERON:0002113	24.56	gold quality
monocyte	CL:0000576	24.52	gold quality
gastrocnemius	UBERON:0001388	24.38	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 12 — C9JPN9 (reviewed: C9JPN9)

All UniProt accessions (1): C9JPN9

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_001243782* (*=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-C9JPN9-F1	67.74	0.45

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

68 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L12	PCBD1	P61457	407
USP17L12	PPP1R3A	Q16821	290
USP17L12	CFAP251	Q8TBY9	257
USP17L12	ATPAF1	Q5TC12	245
USP17L12	LYPD3	O95274	205
USP17L12	MYPN	Q86TC9	182
USP17L12	CHRM3	P20309	158
USP17L12	HBE1	P02100	153
USP17L12	NPTX2	P47972	151
USP17L12	PRODH	O43272	147
USP17L12	RCE1	Q9Y256	112
USP17L12	USP17L22	D6RA61	64
USP17L12	USP17L13	C9JLJ4	52
USP17L12	RNF123	Q5XPI4	49
USP17L12	SUN3	Q8TAQ9	0
USP17L12	CDC25A	P30304	0

IntAct

2 interactions, top by confidence:

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

BioGRID (6): USP17L12 (Affinity Capture-MS), USP17L12 (Positive Genetic), USP17L12 (Synthetic Lethality), USP17L12 (Affinity Capture-MS), USP17L12 (Affinity Capture-MS), USP17L12 (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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

72 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9221442:G:GT	donor_gain	0.5500
4:9221443:A:T	donor_gain	0.5400
4:9221425:TGGA:T	donor_gain	0.4900
4:9221516:CGAAG:C	donor_loss	0.4800
4:9221517:GAAG:G	donor_loss	0.4800
4:9221518:AAGG:A	donor_loss	0.4800
4:9221519:AGG:A	donor_loss	0.4800
4:9221520:GGTA:G	donor_loss	0.4800
4:9221521:G:T	donor_loss	0.4800
4:9221522:T:A	donor_loss	0.4800
4:9221369:A:T	donor_gain	0.4500
4:9221515:TCGAA:T	donor_loss	0.4400
4:9221523:A:C	donor_loss	0.4300
4:9220895:A:T	donor_gain	0.3900
4:9221355:C:T	donor_gain	0.3900
4:9221515:TCGA:T	donor_gain	0.3900
4:9220266:G:GC	acceptor_gain	0.3700
4:9221250:GCC:G	donor_gain	0.3700
4:9221269:T:G	acceptor_gain	0.3600
4:9221428:A:T	donor_gain	0.3400
4:9221426:GGAA:G	donor_gain	0.3300
4:9220359:C:CG	donor_gain	0.3200
4:9220359:C:G	donor_gain	0.3200
4:9221489:G:GT	donor_gain	0.3200
4:9221412:G:GT	donor_gain	0.3100
4:9221133:TG:T	donor_gain	0.2900
4:9221134:GG:G	donor_gain	0.2900
4:9221268:A:AG	acceptor_gain	0.2900
4:9221273:GAAGA:G	acceptor_gain	0.2900
4:9221535:G:GT	donor_gain	0.2900

AlphaMissense

3494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:9221203:A:T	D351V	0.998
4:9221204:T:A	D351E	0.997
4:9221204:T:G	D351E	0.997
4:9220998:T:C	F283L	0.996
4:9221000:C:A	F283L	0.996
4:9221000:C:G	F283L	0.996
4:9220641:T:C	F164L	0.995
4:9220643:T:A	F164L	0.995
4:9220643:T:G	F164L	0.995
4:9221202:G:C	D351H	0.995
4:9221203:A:C	D351A	0.995
4:9220403:T:A	N84K	0.994
4:9220403:T:G	N84K	0.994
4:9221153:T:A	H334Q	0.994
4:9221153:T:G	H334Q	0.994
4:9220631:T:A	D160E	0.993
4:9220631:T:G	D160E	0.993
4:9221149:G:A	G333E	0.993
4:9221187:T:A	W346R	0.992
4:9221187:T:C	W346R	0.992
4:9220608:T:C	F153L	0.991
4:9220610:C:A	F153L	0.991
4:9220610:C:G	F153L	0.991
4:9221149:G:T	G333V	0.991
4:9221203:A:G	D351G	0.991
4:9220402:A:C	N84T	0.990
4:9220427:C:A	N92K	0.990
4:9220427:C:G	N92K	0.990
4:9221124:C:G	H325D	0.990
4:9221151:C:G	H334D	0.990

dbSNP variants (sampled 300 via entrez): RS1000480697 (4:9219794 T>G), RS1156694524 (4:9220017 G>A), RS1161862248 (4:9219304 C>T), RS1162068753 (4:9219730 A>ACC,ACG,ACT), RS1163412274 (4:9220252 G>A), RS1163947675 (4:9219599 C>A,G), RS1164737528 (4:9219885 G>A), RS1165050838 (4:9219607 T>C), RS1165465683 (4:9219654 C>T), RS1165621127 (4:9220230 G>A), RS1166270839 (4:9219489 A>C,T), RS1166431671 (4:9219918 C>A,T), RS1168073808 (4:9220218 T>C,G), RS1168821489 (4:9219789 T>A,G), RS1171557204 (4:9219350 G>C)

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

1 total (human), top 1 by PubMed support.

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

Clinical trials (associated diseases)

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