YOD1

Summary

YOD1 (YOD1 deubiquitinase, HGNC:25035) is a protein-coding gene on chromosome 1q32.1, encoding Ubiquitin thioesterase OTU1 (Q5VVQ6). Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins.

Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. The protein encoded by this gene belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55432 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• Druggable target: yes
• MANE Select transcript: NM_018566

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25035
Approved symbol	YOD1
Name	YOD1 deubiquitinase
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp451J1719, OTUD2, DUBA8
Ensembl gene	ENSG00000180667
Ensembl biotype	protein_coding
OMIM	612023
Entrez	55432

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000315927, ENST00000367084

RefSeq mRNA: 2 — MANE Select: NM_018566 NM_001276320, NM_018566

CCDS: CCDS31002, CCDS60402

Canonical transcript exons

ENST00000315927 — 2 exons

Exon	Start	End
ENSE00001274625	207043849	207049723
ENSE00001274631	207050688	207051208

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8908 / max 912.0919, expressed in 1699 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17155	12.6934	1637
17156	0.5001	184
17158	0.3751	181
17157	0.3222	148

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	96.17	gold quality
trabecular bone tissue	UBERON:0002483	96.10	gold quality
upper leg skin	UBERON:0004262	95.90	gold quality
esophagus squamous epithelium	UBERON:0006920	95.49	gold quality
penis	UBERON:0000989	94.27	gold quality
lower esophagus mucosa	UBERON:0035834	93.04	gold quality
epithelium of esophagus	UBERON:0001976	91.23	gold quality
oral cavity	UBERON:0000167	91.17	gold quality
pharyngeal mucosa	UBERON:0000355	90.35	gold quality
mammalian vulva	UBERON:0000997	90.26	gold quality
bone marrow	UBERON:0002371	90.06	gold quality
gingiva	UBERON:0001828	89.76	gold quality
buccal mucosa cell	CL:0002336	89.59	gold quality
endothelial cell	CL:0000115	89.47	gold quality
gingival epithelium	UBERON:0001949	89.00	gold quality
skin of hip	UBERON:0001554	87.14	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.54	gold quality
esophagus mucosa	UBERON:0002469	85.15	gold quality
sperm	CL:0000019	84.89	gold quality
adrenal tissue	UBERON:0018303	84.86	gold quality
squamous epithelium	UBERON:0006914	84.83	gold quality
epithelium of nasopharynx	UBERON:0001951	84.35	gold quality
monocyte	CL:0000576	84.27	gold quality
skin of leg	UBERON:0001511	84.09	gold quality
pigmented layer of retina	UBERON:0001782	84.04	gold quality
zone of skin	UBERON:0000014	83.98	gold quality
mononuclear cell	CL:0000842	83.96	gold quality
palpebral conjunctiva	UBERON:0001812	83.26	gold quality
leukocyte	CL:0000738	83.25	gold quality
skin of abdomen	UBERON:0001416	82.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	13.66
E-MTAB-9467	no	0.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

294 targeting YOD1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
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-1277-5P	100.00	73.95	5056
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787

Literature-anchored findings (GeneRIF, showing 14)

• The assignment of a p97-associated ubiquitin processing function to YOD1 adds to our understanding of p97’s role in the dislocation of misfolded proteins from the endoplasmic reticulum. (PMID:19818707)
• miR-373 increases proliferation by directly targeting YOD1 in cervical cancer. (PMID:25747718)
• activity of the p97-associated deubiquitinylase YOD1 is also required for substrate disposal (PMID:26463207)
• Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. (PMID:27753622)
• These data define that YOD1 antagonizes TRAF6/p62-dependent IL-1 signaling to NF-kappaB. (PMID:28244869)
• Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances the stability of ITCH, which leads to reduced levels of LATS and a subsequent increase in the YAP/TAZ level. (PMID:28416659)
• Data suggest that YOD1 is a novel regulator of the Hippo pathway, and thereby a potential therapeutic target for liver cancer. (PMID:28502290)
• This study showed that YOD1 overexpression enhances cell migration by promoting TGF-beta3 signaling which may play an important role in lip and palate formation. (PMID:30145984)
• YOD1 RNAi may inhibit cell proliferation and migration associated with the pathogenesis of NSCL/P through TGF-beta3 signaling. The study indicates a novel role of YOD1 in regulating TGF-beta3 signaling to affect cell proliferation and migration resulting in cleft lip with or without cleft palate. (PMID:30345304)
• findings thus provided novel insights into the regulatory cascade of the cellular antiviral response through YOD1-mediated K63-linked deubiquitination and aggregation of MAVS. (PMID:30952814)
• Deubiquitinating enzyme YOD1 deubiquitinates and destabilizes alpha-synuclein. (PMID:36682332)
• YY1-induced LncRNA-TUG1 elevates YOD1 to promote cell proliferation and inhibit bortezomib sensitivity in multiple myeloma. (PMID:37078241)
• Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis. (PMID:37667382)
• YOD1 protects against MRSA sepsis-induced DIC through Lys33-linked deubiquitination of NLRP3. (PMID:38789414)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	yod1	ENSDARG00000008542
mus_musculus	Yod1	ENSMUSG00000046404
drosophila_melanogaster	Yod1	FBGN0035593

Protein

Protein identifiers

Ubiquitin thioesterase OTU1 — Q5VVQ6 (reviewed: Q5VVQ6)

Alternative names: DUBA-8, HIV-1-induced protease 7, OTU domain-containing protein 2

All UniProt accessions (1): Q5VVQ6

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP’s axial channel. Mediates deubiquitination of ‘Lys-27’-, ‘Lys-29’- and ‘Lys-33’-linked polyubiquitin chains. Also able to hydrolyze ‘Lys-11’-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin. May play a role in macroautophagy, regulating for instance the clearance of damaged lysosomes. May recruit PLAA, UBXN6 and VCP to damaged lysosome membranes decorated with K48-linked ubiquitin chains and remove these chains allowing autophagosome formation.

Subunit / interactions. Interacts with VCP; the interaction is direct. Interacts with FAF2/UBXD8. Interacts with DERL1; however interaction is dependent on the UBAX-like region, suggesting that it may be indirect. Interacts with PLAA, UBXN6 and VCP; may form a complex involved in macroautophagy.

Subcellular location. Cytoplasm.

Domain organisation. The UBAX-like region mediates the interaction with VCP. According to PubMed:19818707, it corresponds to a UBX domain, which is a hallmark for VCP-associated proteins. However, no canonical UBX is detected by prediction tools such as Pfam or PROSITE. The C2H2-type zinc finger mediates specificity for ‘Lys-27’-, ‘Lys-29’- and ‘Lys-33’-linked polyubiquitin chains but not for ‘Lys-11’-linked ubiquitin chains. Selectivity for ‘Lys-11’-linked ubiquitin chains is provided by recognition of the sequence surrounding ‘Lys-11’ in ubiquitin. The S2 site region provides specificity for longer ‘Lys-11’-linked ubiquitin chains.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VVQ6-1	1	yes
Q5VVQ6-2	2

RefSeq proteins (2): NP_001263249, NP_061036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003323	OTU_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR048857	OTU1_Ubl	Domain
IPR057766	Znf-C2H2_OTU1-like_C	Domain

Pfam: PF02338, PF21403, PF24560

Enzyme classification (BRENDA):

• EC 3.4.19.12 — ubiquitinyl hydrolase 1 (BRENDA: 30 organisms, 328 substrates, 173 inhibitors, 70 Km, 58 kcat entries)

Substrate kinetics (BRENDA)

29 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UBIQUITIN-7-AMIDO-4-METHYLCOUMARIN	—	7
DABCYL-FKKKGGGDVKE-EDANS	0.0142–0.0616	6
UBIQUITIN 7-AMIDO-4-METHYLCOUMARIN	—	5
UBIQUITIN ETHYL ESTER	0.0006–0.03	5
DABCYL-FRLKGGAPIKGV-EDANS	0.0048–0.0217	3
UBIQUITIN-W-G75A	0.0001–0.0004	2
UBIQUITIN-W-G76A	0.0011–0.002	2
UBIQUITIN-W-H68A	0.0005	2
UBIQUITIN-W-I44A	0.0003–0.0004	2
UBIQUITIN-W-K11A	0.0011–0.0023	2
UBIQUITIN-W-K48A	0.0003–0.0007	2
UBIQUITIN-W-K63A	0.0004–0.0008	2
UBIQUITIN-W-K6A	0.0009–0.0014	2
UBIQUITIN-W-L71A	0.008–0.0198	2
UBIQUITIN-W-L73A	0.0058–0.0104	2

UniProt features (42 total): helix 8, strand 8, region of interest 6, mutagenesis site 5, active site 4, turn 3, sequence conflict 2, chain 1, domain 1, binding site 1, splice variant 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4BOQ	X-RAY DIFFRACTION	1.47
4BOS	X-RAY DIFFRACTION	2.35
4BOZ	X-RAY DIFFRACTION	3.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VVQ6-F1	81.59	0.50

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 (4): 157; 160 (nucleophile); 267; 342

Ligand- & substrate-binding residues (1): 266

Mutagenesis-validated functional residues (5):

Position	Phenotype
160	abolishes deubiquitinase activity without affecting interaction with vcp. specifically blocks a step in the course of di
292	does not affect activity or specificity. impairs ability to cleave longer ’lys-11’-linked ubiquitin chains; when associa
295	does not affect activity or specificity. impairs ability to cleave longer ’lys-11’-linked ubiquitin chains; when associa
336	reduced activity toward ’lys-27’-, ’lys-29’- and ’lys-33’-linked ubiquitin without affecting activity toward ’lys-11’-li
342	reduced activity toward ’lys-27’-, ’lys-29’- and ’lys-33’-linked ubiquitin without affecting activity toward ’lys-11’-li

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5689896	Ovarian tumor domain proteases

MSigDB gene sets: 263 (showing top): WENDT_COHESIN_TARGETS_UP, GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AAGCAAT_MIR137, ACTACCT_MIR196A_MIR196B, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (12): macroautophagy (GO:0016236), endoplasmic reticulum unfolded protein response (GO:0030968), protein K29-linked deubiquitination (GO:0035523), protein K11-linked deubiquitination (GO:0035871), ERAD pathway (GO:0036503), protein K63-linked deubiquitination (GO:0070536), protein K48-linked deubiquitination (GO:0071108), negative regulation of retrograde protein transport, ER to cytosol (GO:1904153), protein K27-linked deubiquitination (GO:1990167), protein K33-linked deubiquitination (GO:1990168), proteolysis (GO:0006508), response to unfolded protein (GO:0006986)

GO Molecular Function (12): cysteine-type deubiquitinase activity (GO:0004843), zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), K63-linked deubiquitinase activity (GO:0061578), deubiquitinase activity (GO:0101005), K48-linked deubiquitinase activity (GO:1990380), catalytic activity (GO:0003824), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), 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
protein deubiquitination	6
deubiquitinase activity	3
response to endoplasmic reticulum stress	2
cellular anatomical structure	2
autophagosome assembly	1
autophagy	1
cellular response to unfolded protein	1
intracellular signal transduction	1
proteasomal protein catabolic process	1
response to chemical	1
retrograde protein transport, ER to cytosol	1
negative regulation of protein exit from endoplasmic reticulum	1
regulation of retrograde protein transport, ER to cytosol	1
protein metabolic process	1
response to topologically incorrect protein	1
cysteine-type peptidase activity	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-like protein peptidase activity	1
molecular_function	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YOD1	UBXN6	Q9BZV1	957
YOD1	ZUP1	Q96AP4	898
YOD1	PLAA	Q9Y263	871
YOD1	VCP	P55072	818
YOD1	USP1	O94782	810
YOD1	ZNF629	Q9UEG4	788
YOD1	ZNF436	Q9C0F3	788
YOD1	K7ESF6	K7ESF6	788
YOD1	ZNF501	Q96CX3	788
YOD1	ZNF44	P15621	787
YOD1	ZNF569	Q5MCW4	786
YOD1	USP13	Q92995	780
YOD1	OTUD6A	Q7L8S5	725
YOD1	ITCH	Q96J02	715
YOD1	ATXN3	P54252	699

IntAct

106 interactions, top by confidence:

A	B	Type	Score
YOD1	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
YOD1	TBX22	psi-mi:“MI:0915”(physical association)	0.560
YOD1	RNF5	psi-mi:“MI:0915”(physical association)	0.560
YOD1	RNF216	psi-mi:“MI:0915”(physical association)	0.560
YOD1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.560
PSMA7	YOD1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
VCP	YOD1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	TRAF6	psi-mi:“MI:0915”(physical association)	0.560
YOD1	TRIM8	psi-mi:“MI:0915”(physical association)	0.560
TP53BP2	YOD1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	UBXN6	psi-mi:“MI:0915”(physical association)	0.560
LMO2	YOD1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	FAM168A	psi-mi:“MI:0915”(physical association)	0.560
UBC	YOD1	psi-mi:“MI:0915”(physical association)	0.560
RFC2	YOD1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	PLEKHB2	psi-mi:“MI:0915”(physical association)	0.560
YOD1	ZFP57	psi-mi:“MI:0915”(physical association)	0.560
YOD1	NGRN	psi-mi:“MI:0915”(physical association)	0.560
YOD1	SPART	psi-mi:“MI:0915”(physical association)	0.560
INCA1	YOD1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	MKRN1	psi-mi:“MI:0915”(physical association)	0.560
CCDC51	TGM5	psi-mi:“MI:0914”(association)	0.530
RBCK1	UMAD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (567): VCP (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS), UFD1L (Affinity Capture-MS), VCP (Reconstituted Complex), UBC (Biochemical Activity), YOD1 (Affinity Capture-MS), FAM98B (Co-fractionation), YOD1 (Co-fractionation), YOD1 (Affinity Capture-MS), YOD1 (Affinity Capture-MS), UBC (Biochemical Activity), YOD1 (Affinity Capture-MS), YOD1 (Affinity Capture-MS), YOD1 (Two-hybrid), TRAF6 (Two-hybrid)

ESM2 similar proteins: A2VE39, A4IG62, C7J0A2, D2HRF1, D3ZVK1, E1BPX4, F4ISQ7, I0IUP3, O61660, O70157, O95985, P30664, P33991, P42285, P49717, P54731, Q0V9Q6, Q13472, Q25AA3, Q26454, Q295E6, Q2T9S3, Q2UM19, Q32Q05, Q5F310, Q5JKB0, Q5R981, Q5VVQ6, Q5XK83, Q5ZJT0, Q6GL41, Q6Z9U7, Q7XQR9, Q803R5, Q8CB27, Q8N1G2, Q921X6, Q924K2, Q9CWV1, Q9CZU3

Diamond homologs: O13974, Q05B57, Q0IH43, Q32Q05, Q55BI3, Q567B1, Q5F3A6, Q5VVQ6, Q8CB27, Q9LPT6, Q9VRJ9, P43558, Q29FC9, Q8GYW0, Q8LBZ4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Defective CFTR causes cystic fibrosis	5	31.4×	2e-04
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	27.6×	2e-04
ABC-family protein mediated transport	5	17.4×	1e-03
Ub-specific processing proteases	5	7.6×	4e-03
Antigen processing: Ubiquitination & Proteasome degradation	6	6.4×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	5	33.9×	1e-04
positive regulation of canonical NF-kappaB signal transduction	8	10.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

165 predictions. Top by Δscore:

Variant	Effect	Δscore
1:207050682:CCTTA:C	donor_loss	1.0000
1:207050683:CTTAC:C	donor_loss	1.0000
1:207050684:TTAC:T	donor_loss	1.0000
1:207050685:TACCA:T	donor_loss	1.0000
1:207050686:A:AC	donor_gain	1.0000
1:207050686:A:C	donor_loss	1.0000
1:207050687:C:CA	donor_loss	1.0000
1:207050687:C:CC	donor_gain	1.0000
1:207050687:CCAG:C	donor_gain	1.0000
1:207050687:CCAGA:C	donor_gain	1.0000
1:207050708:T:TA	donor_gain	1.0000
1:207050686:AC:A	donor_gain	0.9900
1:207050687:CC:C	donor_gain	0.9900
1:207050687:CCA:C	donor_gain	0.9900
1:207049722:ACCT:A	acceptor_loss	0.9700
1:207049723:CCTGT:C	acceptor_loss	0.9700
1:207049724:C:CA	acceptor_loss	0.9700
1:207049725:T:A	acceptor_loss	0.9700
1:207049724:C:CC	acceptor_gain	0.9300
1:207049721:CAC:C	acceptor_gain	0.9200
1:207048951:G:C	donor_gain	0.8500
1:207049657:C:CT	donor_gain	0.8400
1:207049720:TCAC:T	acceptor_gain	0.8100
1:207049721:CACC:C	acceptor_gain	0.8100
1:207049100:A:T	donor_gain	0.7900
1:207049647:A:C	donor_gain	0.7900
1:207049727:T:C	acceptor_gain	0.7900
1:207049719:GTCAC:G	acceptor_gain	0.7800
1:207050681:T:TA	donor_gain	0.7700
1:207049727:T:TC	acceptor_gain	0.7200

AlphaMissense

2267 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:207049410:C:A	W219C	1.000
1:207049410:C:G	W219C	1.000
1:207049412:A:G	W219R	1.000
1:207049412:A:T	W219R	1.000
1:207049137:A:C	F310L	0.999
1:207049137:A:T	F310L	0.999
1:207049139:A:G	F310L	0.999
1:207049255:A:T	L271H	0.999
1:207049268:G:C	H267D	0.999
1:207049320:A:C	F249L	0.999
1:207049320:A:T	F249L	0.999
1:207049322:A:G	F249L	0.999
1:207049396:T:A	E224V	0.999
1:207049442:A:G	Y209H	0.999
1:207049518:T:A	R183S	0.999
1:207049518:T:G	R183S	0.999
1:207049519:C:A	R183I	0.999
1:207049519:C:G	R183T	0.999
1:207049575:A:C	S164R	0.999
1:207049575:A:T	S164R	0.999
1:207049577:T:G	S164R	0.999
1:207049581:A:C	F162L	0.999
1:207049581:A:T	F162L	0.999
1:207049583:A:G	F162L	0.999
1:207049592:A:G	S159P	0.999
1:207049032:A:C	F345L	0.998
1:207049032:A:T	F345L	0.998
1:207049034:A:G	F345L	0.998
1:207049109:A:G	C320R	0.998
1:207049178:C:G	A297P	0.998

dbSNP variants (sampled 300 via entrez): RS1000858662 (1:207049291 A>C,G), RS1000962571 (1:207055099 T>G), RS1001052639 (1:207051120 G>A,C), RS1001399195 (1:207048988 G>A), RS1001459953 (1:207044811 GC>G), RS1002112108 (1:207050096 C>T), RS1002845517 (1:207048004 A>C), RS1002866294 (1:207046044 G>A), RS1002976412 (1:207052333 G>A,C,T), RS1003314898 (1:207051026 A>C), RS1003327915 (1:207045852 G>A,T), RS1003346242 (1:207051183 C>T), RS1003847234 (1:207046518 A>C), RS1004371867 (1:207046471 A>G), RS1004739887 (1:207045417 T>C)

Disease associations

OMIM: gene MIM:612023 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007829_4	Systolic blood pressure	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006944	systolic blood pressure change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630833 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Copper	affects binding, increases expression	1
Curcumin	decreases expression	1
Doxorubicin	affects expression	1
Gold	decreases expression	1
Indomethacin	decreases expression	1
Lead	affects methylation	1
Melphalan	increases expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4605994	Binding	Inhibition of human GST-tagged OTU1 expressed in Escherichia coli assessed as cleavage of Ubiquitin-Rhodamine110-glycine to Ubiquitin and Rhodamine110-glycine using Ubiquitin-Rhodamine110-glycine as substrate by fluorescence based analysis	Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with In Vivo Antitumor Activity. — J Med Chem

Clinical trials (associated diseases)

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