USP17L4

Summary

USP17L4 (ubiquitin specific peptidase 17 like family member 4, HGNC:37176) is a protein-coding gene on chromosome 8p23.1, encoding Inactive ubiquitin carboxyl-terminal hydrolase 17-like protein 4 (A6NCW7).

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 645402 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001256874

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37176
Approved symbol	USP17L4
Name	ubiquitin specific peptidase 17 like family member 4
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000236125
Ensembl biotype	protein_coding
Entrez	645402

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000526929

RefSeq mRNA: 1 — MANE Select: NM_001256874 NM_001256874

CCDS: CCDS78299

Canonical transcript exons

ENST00000526929 — 1 exons

Exon	Start	End
ENSE00002187836	7337115	7338707

Expression profiles

Bgee: expression breadth tissue_specific, 2 present calls, max score 43.54.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	43.54	gold quality
skeletal muscle tissue	UBERON:0001134	41.77	gold quality
colonic epithelium	UBERON:0000397	41.09	gold quality
bone marrow cell	CL:0002092	40.65	gold quality
sural nerve	UBERON:0015488	39.85	gold quality
muscle tissue	UBERON:0002385	37.23	gold quality
calcaneal tendon	UBERON:0003701	36.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.68	gold quality
corpus callosum	UBERON:0002336	34.87	gold quality
bone marrow	UBERON:0002371	34.03	gold quality
superior frontal gyrus	UBERON:0002661	33.61	gold quality
mucosa of stomach	UBERON:0001199	33.26	gold quality
tonsil	UBERON:0002372	33.26	gold quality
primary visual cortex	UBERON:0002436	30.07	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
monocyte	CL:0000576	29.44	gold quality
leukocyte	CL:0000738	29.28	gold quality
placenta	UBERON:0001987	29.08	gold quality
liver	UBERON:0002107	29.00	gold quality
gall bladder	UBERON:0002110	28.63	silver quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
islet of Langerhans	UBERON:0000006	27.28	gold quality
muscle of leg	UBERON:0001383	27.27	gold quality
myometrium	UBERON:0001296	26.66	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
skin of abdomen	UBERON:0001416	26.01	gold quality
kidney	UBERON:0002113	25.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
pancreas	UBERON:0001264	25.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

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

Inactive ubiquitin carboxyl-terminal hydrolase 17-like protein 4 — A6NCW7 (reviewed: A6NCW7)

All UniProt accessions (1): A6NCW7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Endoplasmic reticulum.

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

RefSeq proteins (1): NP_001243803* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00443

UniProt features (7 total): compositionally biased region 3, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NCW7-F1	67.32	0.45

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, 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, chr8p23

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 (1): cysteine-type deubiquitinase activity (GO:0004843)

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
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

78 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP17L4	FAM90A10	A6NDY2	762
USP17L4	DEFB108B	Q8NET1	594
USP17L4	DEFB107A	Q8IZN7	584
USP17L4	DEFB106A	Q8N104	524
USP17L4	DEFB105A	Q8NG35	518
USP17L4	PRR23B	Q6ZRT6	479
USP17L4	PRR23D1	E9PI22	477
USP17L4	PRR23A	A6NEV1	476
USP17L4	A0A0G2JN59	A0A0G2JN59	447
USP17L4	PRR23C	Q6ZRP0	418
USP17L4	DEFB104A	Q8WTQ1	306
USP17L4	JOSD1	Q15040	301
USP17L4	DEFB103A	P81534	232
USP17L4	ZUP1	Q96AP4	231
USP17L4	RCE1	Q9Y256	202

IntAct

0 interactions, top by confidence:

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, B1AQJ2, B2RQC2, B3M3M6, B3NC86, B4HUI5, B4IXE0, B4KXJ5, B4LG38, B4MLR8, B4PIW8

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

104 predictions. Top by Δscore:

Variant	Effect	Δscore
8:7338213:GCC:G	donor_gain	0.5100
8:7338406:A:T	donor_gain	0.4700
8:7338151:G:GA	donor_gain	0.4500
8:7338096:TG:T	donor_gain	0.4300
8:7338097:GG:G	donor_gain	0.4300
8:7338236:GAAGA:G	acceptor_gain	0.4100
8:7338146:C:T	donor_gain	0.3900
8:7338263:G:GT	donor_gain	0.3900
8:7338332:A:T	donor_gain	0.3900
8:7337229:G:GC	acceptor_gain	0.3800
8:7338405:G:GT	donor_gain	0.3800
8:7337858:A:T	donor_gain	0.3700
8:7338235:A:AG	acceptor_gain	0.3700
8:7338236:G:GG	acceptor_gain	0.3700
8:7337322:C:CG	donor_gain	0.3600
8:7338232:T:G	acceptor_gain	0.3600
8:7338258:A:AG	donor_gain	0.3600
8:7338259:G:GG	donor_gain	0.3600
8:7337322:C:G	donor_gain	0.3500
8:7337978:C:T	donor_gain	0.3500
8:7338178:C:G	donor_gain	0.3500
8:7338176:C:A	donor_gain	0.3400
8:7338231:A:AG	acceptor_gain	0.3400
8:7338388:TGGA:T	donor_gain	0.3400
8:7338479:TGAAG:T	donor_loss	0.3400
8:7338480:GAAGG:G	donor_loss	0.3400
8:7338481:AAG:A	donor_loss	0.3400
8:7338482:AGG:A	donor_loss	0.3400
8:7338483:GG:G	donor_loss	0.3400
8:7338484:G:T	donor_loss	0.3400

AlphaMissense

3505 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:7337703:T:C	F197L	0.859
8:7337705:T:A	F197L	0.859
8:7337705:T:G	F197L	0.859
8:7337604:T:C	F164L	0.849
8:7337606:T:A	F164L	0.849
8:7337606:T:G	F164L	0.849
8:7338225:T:C	F371L	0.814
8:7338227:T:A	F371L	0.814
8:7338227:T:G	F371L	0.814
8:7337571:T:C	F153L	0.804
8:7337573:C:A	F153L	0.804
8:7337573:C:G	F153L	0.804
8:7337961:T:C	F283L	0.801
8:7337963:C:A	F283L	0.801
8:7337963:C:G	F283L	0.801
8:7338150:T:A	W346R	0.756
8:7338150:T:C	W346R	0.756
8:7337613:T:C	F167L	0.754
8:7337615:C:A	F167L	0.754
8:7337615:C:G	F167L	0.754
8:7337763:T:C	F217L	0.675
8:7337765:T:A	F217L	0.675
8:7337765:T:G	F217L	0.675
8:7338152:G:C	W346C	0.657
8:7338152:G:T	W346C	0.657
8:7338134:A:C	K340N	0.632
8:7338134:A:T	K340N	0.632
8:7337701:T:A	I196K	0.627
8:7337808:A:C	S232R	0.618
8:7337810:T:A	S232R	0.618

dbSNP variants (sampled 300 via entrez): RS1001819009 (8:7337154 T>C), RS1002084764 (8:7336761 C>G,T), RS1003898352 (8:7335661 T>C), RS1005657151 (8:7338314 C>G), RS1006041695 (8:7338951 G>A), RS1007747066 (8:7335975 G>A), RS1011825312 (8:7336616 GA>G), RS1012879915 (8:7335558 C>T), RS1017268571 (8:7335985 G>A,T), RS1017737846 (8:7336257 C>G,T), RS1018325854 (8:7338968 G>A), RS1021791766 (8:7336406 G>C,T), RS1022259406 (8:7336658 A>C,G,T), RS1025644571 (8:7337334 A>G), RS1027324920 (8:7335723 C>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)

Clinical trials (associated diseases)

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