USP17L20

Summary

USP17L20 (ubiquitin specific peptidase 17 like family member 20, HGNC:44448) is a protein-coding gene on chromosome 4p16.1, encoding Ubiquitin carboxyl-terminal hydrolase 17-like protein 20 (D6RJB6). 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 100287441 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001256861

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44448
Approved symbol	USP17L20
Name	ubiquitin specific peptidase 17 like family member 20
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000250745
Ensembl biotype	protein_coding
Entrez	100287441

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000506151

RefSeq mRNA: 12 — MANE Select: NM_001256861 NM_001256861, NM_001421629, NM_001421630, NM_001421634, NM_001421688, NM_001421905, NM_001421913, NM_001421916, NM_001421920, NM_001421921, NM_001421923, NM_001421928

CCDS: CCDS59461

Canonical transcript exons

ENST00000506151 — 1 exons

Exon	Start	End
ENSE00002065036	9258124	9259716

Expression profiles

Bgee: expression breadth broad, 18 present calls, max score 38.78.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	38.78	gold quality
colonic epithelium	UBERON:0000397	37.20	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
sural nerve	UBERON:0015488	35.43	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	32.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
primary visual cortex	UBERON:0002436	32.14	silver quality
muscle tissue	UBERON:0002385	31.06	gold quality
urinary bladder	UBERON:0001255	30.91	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.73	gold quality
monocyte	CL:0000576	29.15	gold quality
leukocyte	CL:0000738	29.01	gold quality
duodenum	UBERON:0002114	28.14	gold quality
islet of Langerhans	UBERON:0000006	27.57	gold quality
lymph node	UBERON:0000029	27.57	gold quality
blood	UBERON:0000178	27.26	silver quality
tonsil	UBERON:0002372	27.05	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
frontal cortex	UBERON:0001870	26.04	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	25.71	gold quality
endocervix	UBERON:0000458	25.21	silver quality
pancreas	UBERON:0001264	25.07	gold quality
gastrocnemius	UBERON:0001388	24.61	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 20 — D6RJB6 (reviewed: D6RJB6)

All UniProt accessions (1): D6RJB6

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 (12): NP_001243790, NP_001408558, NP_001408559, NP_001408563, NP_001408617, NP_001408834, 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 (9 total): compositionally biased region 3, region of interest 2, active site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-D6RJB6-F1	68.10	0.44

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)

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

60 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L20	ZNF587B	E7ETH6	625
USP17L20	POTEC	B2RU33	603
USP17L20	SEMA4G	Q9NTN9	447
USP17L20	SULF1	Q8IWU6	289
USP17L20	RCE1	Q9Y256	243
USP17L20	STAMBP	O95630	183
USP17L20	USP4	Q13107	164
USP17L20	PSMD14	O00487	152
USP17L20	CDC25A	P30304	73
USP17L20	USP17L22	D6RA61	73
USP17L20	USP17L11	C9JVI0	49
USP17L20	USP17L25	Q0WX57	46
USP17L20	USP17L2	Q6R6M4	45
USP17L20	SUN3	Q8TAQ9	0
USP17L20	RIGI	O95786	0
USP17L20	USP17L12	C9JPN9	0
USP17L20	USP17L10	C9JJH3	0

IntAct

2 interactions, top by confidence:

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

BioGRID (5): USP17L20 (Positive Genetic), USP17L20 (Affinity Capture-MS), USP17L20 (Affinity Capture-MS), USP17L20 (Affinity Capture-MS), USP17L20 (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

68 predictions. Top by Δscore:

Variant	Effect	Δscore
4:9259414:G:GT	donor_gain	0.5300
4:9259415:A:T	donor_gain	0.5200
4:9259397:TGGA:T	donor_gain	0.4900
4:9259488:CGAAG:C	donor_loss	0.4700
4:9259489:GAAG:G	donor_loss	0.4700
4:9259490:AAG:A	donor_loss	0.4700
4:9259491:AG:A	donor_loss	0.4700
4:9259492:GGTAC:G	donor_loss	0.4700
4:9259493:GTA:G	donor_loss	0.4700
4:9259494:T:G	donor_loss	0.4700
4:9259341:A:T	donor_gain	0.4500
4:9259487:TCGAA:T	donor_loss	0.4400
4:9259495:A:C	donor_loss	0.4300
4:9258238:G:GC	acceptor_gain	0.4200
4:9259487:TCGA:T	donor_gain	0.3900
4:9259327:C:T	donor_gain	0.3700
4:9259241:T:G	acceptor_gain	0.3600
4:9258391:T:TA	acceptor_gain	0.3500
4:9258392:A:AA	acceptor_gain	0.3500
4:9259222:GCC:G	donor_gain	0.3500
4:9258331:C:CG	donor_gain	0.3300
4:9258331:C:G	donor_gain	0.3300
4:9259398:GGAA:G	donor_gain	0.3300
4:9259400:A:T	donor_gain	0.3300
4:9259384:G:GT	donor_gain	0.3100
4:9259461:G:GT	donor_gain	0.3100
4:9258318:G:GT	donor_gain	0.3000
4:9258867:A:T	donor_gain	0.3000
4:9259240:A:AG	acceptor_gain	0.3000
4:9259105:TG:T	donor_gain	0.2900

AlphaMissense

3495 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:9258970:T:C	F283L	0.998
4:9258972:C:A	F283L	0.998
4:9258972:C:G	F283L	0.998
4:9259175:A:T	D351V	0.996
4:9259176:T:A	D351E	0.996
4:9259176:T:G	D351E	0.996
4:9259159:T:A	W346R	0.995
4:9259159:T:C	W346R	0.995
4:9258375:T:A	N84K	0.993
4:9258375:T:G	N84K	0.993
4:9258613:T:C	F164L	0.993
4:9258615:T:A	F164L	0.993
4:9258615:T:G	F164L	0.993
4:9259174:G:C	D351H	0.993
4:9259175:A:C	D351A	0.993
4:9258365:G:A	G81E	0.991
4:9258399:C:A	N92K	0.991
4:9258399:C:G	N92K	0.991
4:9258580:T:C	F153L	0.991
4:9258582:C:A	F153L	0.991
4:9258582:C:G	F153L	0.991
4:9259121:G:A	G333E	0.991
4:9259125:T:A	H334Q	0.990
4:9259125:T:G	H334Q	0.990
4:9259161:G:C	W346C	0.990
4:9259161:G:T	W346C	0.990
4:9258364:G:T	G81W	0.989
4:9258603:T:A	D160E	0.989
4:9258603:T:G	D160E	0.989
4:9258911:C:A	A263D	0.989

dbSNP variants (sampled 300 via entrez): RS1160672085 (4:9257387 C>A,G,T), RS1160878416 (4:9258018 A>T), RS1161279559 (4:9257385 T>C), RS1162140063 (4:9259278 G>C), RS1165011425 (4:9259582 C>T), RS1167698786 (4:9260207 A>G), RS1173575267 (4:9257108 G>T), RS1174536635 (4:9259728 G>A), RS1177296693 (4:9257471 A>C), RS1177702275 (4:9257783 A>G), RS1180800749 (4:9259563 T>C,G), RS1180925659 (4:9259615 G>A,C), RS1183029944 (4:9257335 C>A,G), RS1184427307 (4:9257679 C>CCA), RS1185144567 (4:9259365 C>A,T)

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.