DESI1

Summary

DESI1 (desumoylating isopeptidase 1, HGNC:24577) is a protein-coding gene on chromosome 22q13.2, encoding Desumoylating isopeptidase 1 (Q6ICB0). Protease which deconjugates SUMO1, SUMO2 and SUMO3 from some substrate proteins.

Enables importin-alpha family protein binding activity and long-chain fatty acyl-CoA hydrolase activity. Involved in protein export from nucleus and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in cytosol. Part of protein-containing complex.

Source: NCBI Gene 27351 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 25 total
• MANE Select transcript: NM_015704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24577
Approved symbol	DESI1
Name	desumoylating isopeptidase 1
Location	22q13.2
Locus type	gene with protein product
Status	Approved
Aliases	D15Wsu75e, DESI-1, POST
Ensembl gene	ENSG00000100418
Ensembl biotype	protein_coding
OMIM	614637
Entrez	27351

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000263256, ENST00000463886, ENST00000468151, ENST00000482612, ENST00000881058, ENST00000938248

RefSeq mRNA: 1 — MANE Select: NM_015704 NM_015704

CCDS: CCDS33652

Canonical transcript exons

ENST00000263256 — 6 exons

Exon	Start	End
ENSE00001048528	41607262	41607331
ENSE00001175973	41607840	41607861
ENSE00001202183	41620752	41621043
ENSE00001286065	41604044	41604153
ENSE00001931328	41598028	41601190
ENSE00003511707	41603259	41603381

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.4453 / max 359.7967, expressed in 1824 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194371	77.4453	1824

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.12	gold quality
left testis	UBERON:0004533	94.32	gold quality
right lobe of liver	UBERON:0001114	94.30	gold quality
right testis	UBERON:0004534	94.30	gold quality
right atrium auricular region	UBERON:0006631	94.05	gold quality
cardiac atrium	UBERON:0002081	93.30	gold quality
testis	UBERON:0000473	92.71	gold quality
colonic epithelium	UBERON:0000397	92.57	gold quality
esophagus mucosa	UBERON:0002469	91.87	gold quality
medial globus pallidus	UBERON:0002477	91.76	gold quality
prefrontal cortex	UBERON:0000451	91.50	gold quality
globus pallidus	UBERON:0001875	91.31	gold quality
right frontal lobe	UBERON:0002810	91.20	gold quality
nucleus accumbens	UBERON:0001882	90.93	gold quality
lateral globus pallidus	UBERON:0002476	90.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.90	gold quality
liver	UBERON:0002107	90.85	gold quality
apex of heart	UBERON:0002098	90.77	gold quality
caudate nucleus	UBERON:0001873	90.67	gold quality
putamen	UBERON:0001874	90.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.62	gold quality
heart left ventricle	UBERON:0002084	90.59	gold quality
cortical plate	UBERON:0005343	90.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.34	gold quality
heart	UBERON:0000948	90.23	gold quality
cardiac ventricle	UBERON:0002082	90.20	gold quality
esophagus	UBERON:0001043	90.15	gold quality
amygdala	UBERON:0001876	90.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.06	gold quality
substantia nigra	UBERON:0002038	89.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

183 targeting DESI1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-3119	99.92	71.34	2390

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	desi1a	ENSDARG00000033140
danio_rerio	desi1b	ENSDARG00000089529
mus_musculus	Desi1	ENSMUSG00000022472
rattus_norvegicus	Desi1	ENSRNOG00000005577
drosophila_melanogaster	CG6972	FBGN0039008

Paralogs (1): DESI2 (ENSG00000121644)

Protein

Protein identifiers

Desumoylating isopeptidase 1 — Q6ICB0 (reviewed: Q6ICB0)

Alternative names: PPPDE peptidase domain-containing protein 2, Palmitoyl protein thioesterase DESI1, Polyubiquitinated substrate transporter, S-depalmitoylase DESI1

All UniProt accessions (1): Q6ICB0

UniProt curated annotations — full annotation on UniProt →

Function. Protease which deconjugates SUMO1, SUMO2 and SUMO3 from some substrate proteins. Has isopeptidase but not SUMO-processing activity. Desumoylates ZBTB46. Collaborates with UBQLN4 in the export of ubiquitinated proteins from the nucleus to the cytoplasm. Exhibits palmitoyl protein thioesterase (S-depalmitoylation) activity towards synthetic substrates 4-methylumbelliferyl-6-S-palmitoyl-beta-D-glucopyranoside and S-depalmitoylation probe 5 (DPP-5).

Subunit / interactions. Homodimer. Interacts with UBQLN4; leading to the export of UBQLN4 from the nucleus.

Subcellular location. Cytoplasm. Nucleus.

Activity regulation. Palmostatin B inhibits its palmitoyl protein thioesterase activity.

Similarity. Belongs to the DeSI family.

RefSeq proteins (1): NP_056519* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008580	PPPDE_dom	Domain
IPR042266	PPPDE_sf	Homologous_superfamily

Pfam: PF05903

Catalyzed reactions (Rhea), 1 shown:

• S-hexadecanoyl-L-cysteinyl-[protein] + H2O = L-cysteinyl-[protein] + hexadecanoate + H(+) (RHEA:19233)

UniProt features (22 total): helix 7, strand 5, turn 4, short sequence motif 2, active site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3EBQ	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ICB0-F1	93.68	0.93

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): 38; 108

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 235 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BASSO_B_LYMPHOCYTE_NETWORK, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_MACROMOLECULE_DEACYLATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_NUCLEAR_TRANSPORT, GOBP_PEPTIDYL_LYSINE_MODIFICATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY

GO Biological Process (5): proteolysis (GO:0006508), protein export from nucleus (GO:0006611), protein desumoylation (GO:0016926), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), macromolecule depalmitoylation (GO:0098734)

GO Molecular Function (8): palmitoyl-(protein) hydrolase activity (GO:0008474), deSUMOylase activity (GO:0016929), identical protein binding (GO:0042802), long-chain fatty acyl-CoA hydrolase activity (GO:0052816), importin-alpha family protein binding (GO:0061676), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), protein-containing complex (GO:0032991), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity, acting on a protein	2
protein binding	2
cellular anatomical structure	2
protein metabolic process	1
intracellular protein transport	1
nuclear export	1
peptidyl-lysine modification	1
protein modification by small protein removal	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
macromolecule deacylation	1
thiolester hydrolase activity	1
palmitoyl hydrolase activity	1
cysteine-type peptidase activity	1
ubiquitin-like protein peptidase activity	1
fatty acyl-CoA hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DESI1	USPL1	Q5W0Q7	832
DESI1	SENP1	Q9P0U3	719
DESI1	SENP5	Q96HI0	714
DESI1	SENP7	Q9BQF6	645
DESI1	SENP6	Q9GZR1	642
DESI1	SUMO1	P55856	626
DESI1	SENP3	Q9H4L4	613
DESI1	SUMO2	P55855	600
DESI1	UBQLN4	Q9NRR5	566
DESI1	SAE1	Q9UBE0	557
DESI1	UBE2I	P50550	494
DESI1	UBA2	Q9UBT2	468
DESI1	SUMO4	Q6EEV6	456
DESI1	BPNT1	O95861	419
DESI1	TIMM29	Q9BSF4	415
DESI1	NICN1	Q9BSH3	415

IntAct

118 interactions, top by confidence:

A	B	Type	Score
DESI1	CDIP1	psi-mi:“MI:0915”(physical association)	0.600
UBA52	DESI1	psi-mi:“MI:0915”(physical association)	0.600
DESI1	SHISA5	psi-mi:“MI:0915”(physical association)	0.560
DESI1	KLRF1	psi-mi:“MI:0915”(physical association)	0.560
DESI1	SMIM21	psi-mi:“MI:0915”(physical association)	0.560
DESI1	SHISA4	psi-mi:“MI:0915”(physical association)	0.560
DESI1		psi-mi:“MI:0915”(physical association)	0.560
DESI1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
DESI1	UBQLNL	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	DESI1	psi-mi:“MI:0915”(physical association)	0.560
DESI1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
DAZAP2	DESI1	psi-mi:“MI:0915”(physical association)	0.560
DESI1	ABI3	psi-mi:“MI:0915”(physical association)	0.560
NME3	DESI1	psi-mi:“MI:0915”(physical association)	0.560
	DESI1	psi-mi:“MI:0915”(physical association)	0.560
UBC	DESI1	psi-mi:“MI:0915”(physical association)	0.560
CTAG1A	DESI1	psi-mi:“MI:0915”(physical association)	0.560
TAS2R41	DESI1	psi-mi:“MI:0915”(physical association)	0.560
CTAG2	DESI1	psi-mi:“MI:0915”(physical association)	0.560
DESI1	NT5C3A	psi-mi:“MI:0915”(physical association)	0.560
RPS27A	DESI1	psi-mi:“MI:0915”(physical association)	0.560
UBB	DESI1	psi-mi:“MI:0915”(physical association)	0.560
ERP29	DESI1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (75): DESI1 (Affinity Capture-RNA), DESI1 (Affinity Capture-RNA), DESI1 (Affinity Capture-MS), DESI1 (Affinity Capture-MS), UBQLN4 (Affinity Capture-MS), UBQLN1 (Affinity Capture-MS), UBQLN2 (Affinity Capture-MS), BAG6 (Affinity Capture-MS), HNRNPK (Affinity Capture-MS), PSMA1 (Affinity Capture-MS), PSMA2 (Affinity Capture-MS), PSMA4 (Affinity Capture-MS), PSMA5 (Affinity Capture-MS), PSMA6 (Affinity Capture-MS), PSMA7 (Affinity Capture-MS)

ESM2 similar proteins: A2YQ56, A3QRX8, A6NHC0, O08529, O14815, O35350, O35920, P00789, P07384, P17569, P17655, P20807, P35750, P36776, P39866, P93648, P93655, P97571, Q07009, Q07093, Q11002, Q27970, Q27971, Q4KM30, Q59HJ6, Q5NVS7, Q5PQ09, Q5R456, Q5XIT6, Q5ZIV7, Q641Z6, Q69UZ3, Q6DC39, Q6GLM5, Q6ICB0, Q78EJ9, Q8CGK3, Q8X1T0, Q91VA3, Q92178

Diamond homologs: A3QRX8, H2KZK4, Q4KM30, Q5PQ09, Q5R456, Q5XIT6, Q5ZIV7, Q6DC39, Q6GLM5, Q6ICB0, Q8X1T0, Q93VG8, Q9BSY9, Q9CQT7, Q9D291

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	142.8×	2e-08
RAS processing	5	119.0×	3e-08
Recognition of DNA damage by PCNA-containing replication complex	5	95.2×	6e-08
Downregulation of SMAD2/3:SMAD4 transcriptional activity	5	92.1×	6e-08
Negative regulation of FGFR2 signaling	5	92.1×	6e-08
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	5	77.2×	9e-08
Regulation of TP53 Degradation	5	73.2×	1e-07
Fanconi Anemia Pathway	5	69.6×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1061 predictions. Top by Δscore:

Variant	Effect	Δscore
22:41603252:CACTT:C	donor_loss	1.0000
22:41603253:ACTTA:A	donor_loss	1.0000
22:41603254:CTTA:C	donor_loss	1.0000
22:41603255:TTA:T	donor_loss	1.0000
22:41603256:TA:T	donor_loss	1.0000
22:41603257:A:AC	donor_gain	1.0000
22:41603258:C:CA	donor_loss	1.0000
22:41603258:C:CC	donor_gain	1.0000
22:41603377:CACCT:C	acceptor_gain	1.0000
22:41603382:C:CC	acceptor_gain	1.0000
22:41603389:T:C	acceptor_gain	1.0000
22:41603389:T:TC	acceptor_gain	1.0000
22:41604152:CC:C	acceptor_gain	1.0000
22:41604153:CC:C	acceptor_gain	1.0000
22:41607332:C:CC	acceptor_gain	1.0000
22:41603258:CG:C	donor_gain	0.9900
22:41603258:CGT:C	donor_gain	0.9900
22:41603258:CGTG:C	donor_gain	0.9900
22:41603258:CGTGG:C	donor_gain	0.9900
22:41603378:ACCT:A	acceptor_gain	0.9900
22:41603379:CCTC:C	acceptor_gain	0.9900
22:41603380:CT:C	acceptor_gain	0.9900
22:41603387:CAT:C	acceptor_gain	0.9900
22:41603388:A:C	acceptor_gain	0.9900
22:41603398:T:C	acceptor_gain	0.9900
22:41603398:T:TC	acceptor_gain	0.9900
22:41603407:A:C	acceptor_gain	0.9900
22:41604036:CCACT:C	donor_loss	0.9900
22:41604037:CACTC:C	donor_loss	0.9900
22:41604038:ACTC:A	donor_loss	0.9900

AlphaMissense

1083 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:41603289:A:T	I128N	0.999
22:41603316:A:G	L119P	0.999
22:41603318:G:C	F118L	0.999
22:41603318:G:T	F118L	0.999
22:41603320:A:G	F118L	0.999
22:41603336:G:C	S112R	0.999
22:41603336:G:T	S112R	0.999
22:41603338:T:G	S112R	0.999
22:41603340:A:G	F111S	0.999
22:41603349:C:T	C108Y	0.999
22:41603351:A:C	N107K	0.999
22:41603351:A:T	N107K	0.999
22:41607323:G:A	S40F	0.999
22:41607323:G:T	S40Y	0.999
22:41607324:A:G	S40P	0.999
22:41603280:A:G	L131P	0.998
22:41603316:A:T	L119Q	0.998
22:41603319:A:G	F118S	0.998
22:41603326:C:G	A116P	0.998
22:41603339:G:C	F111L	0.998
22:41603339:G:T	F111L	0.998
22:41603341:A:G	F111L	0.998
22:41603345:G:C	N109K	0.998
22:41603345:G:T	N109K	0.998
22:41603348:A:C	C108W	0.998
22:41603349:C:A	C108F	0.998
22:41603350:A:G	C108R	0.998
22:41604046:G:C	F96L	0.998
22:41604046:G:T	F96L	0.998
22:41604048:A:G	F96L	0.998

dbSNP variants (sampled 300 via entrez): RS1000161228 (22:41598632 A>G), RS1000186875 (22:41598345 G>T), RS1000268530 (22:41604956 C>G,T), RS1000342364 (22:41604657 C>A,T), RS1000452511 (22:41611219 T>C), RS1000481367 (22:41610972 A>T), RS1000485176 (22:41609100 C>G,T), RS1000866520 (22:41616323 A>C), RS1000939693 (22:41616057 A>G), RS1001098621 (22:41621850 G>A,C,T), RS1001159425 (22:41620528 C>A), RS1001163622 (22:41611854 G>A), RS1001276086 (22:41620696 C>A,T), RS1001353971 (22:41607273 T>C), RS1001425467 (22:41622241 C>T)

Disease associations

OMIM: gene MIM:614637 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005232_52	Neuroticism	3.000000e-18
GCST006269_1195	General cognitive ability	4.000000e-08
GCST010002_83	Refractive error	2.000000e-27
GCST010143_2	Meat-related diet	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004337	intelligence
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	3
Estradiol	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases expression	1
Diuron	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Isotretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2VU	Abcam HEK293T DESI1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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