OTUB2
gene geneOn this page
Also known as FLJ21916MGC3102
Summary
OTUB2 (OTU deubiquitinase, ubiquitin aldehyde binding 2, HGNC:20351) is a protein-coding gene on chromosome 14q32.12, encoding Ubiquitin thioesterase OTUB2 (Q96DC9). Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation.
This gene encodes one of several deubiquitylating enzymes. Ubiquitin modification of proteins is needed for their stability and function; to reverse the process, deubiquityling enzymes remove ubiquitin. This protein contains an OTU domain and binds Ubal (ubiquitin aldehyde); an active cysteine protease site is present in the OTU domain.
Source: NCBI Gene 78990 — RefSeq curated summary.
At a glance
- GWAS associations: 1
- Clinical variants (ClinVar): 37 total
- Druggable target: yes
- MANE Select transcript:
NM_023112
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:20351 |
| Approved symbol | OTUB2 |
| Name | OTU deubiquitinase, ubiquitin aldehyde binding 2 |
| Location | 14q32.12 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | FLJ21916, MGC3102 |
| Ensembl gene | ENSG00000089723 |
| Ensembl biotype | protein_coding |
| OMIM | 608338 |
| Entrez | 78990 |
Gene structure
Transcript identifiers
Ensembl transcripts: 3 — 3 protein_coding
ENST00000203664, ENST00000553723, ENST00000898114
RefSeq mRNA: 1 — MANE Select: NM_023112
NM_023112
CCDS: CCDS9917
Canonical transcript exons
ENST00000203664 — 6 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000659975 | 94038963 | 94039081 |
| ENSE00000659976 | 94043971 | 94044055 |
| ENSE00000808725 | 94037380 | 94037475 |
| ENSE00001174850 | 94044586 | 94044780 |
| ENSE00001402552 | 94045716 | 94048930 |
| ENSE00002438899 | 94026340 | 94026540 |
Expression profiles
Bgee: expression breadth ubiquitous, 129 present calls, max score 81.13.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.2317 / max 61.7986, expressed in 1181 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 141198 | 1.6949 | 1037 |
| 141199 | 0.2783 | 144 |
| 141200 | 0.2585 | 144 |
Top tissues by expression
133 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 81.13 | gold quality |
| left testis | UBERON:0004533 | 78.90 | gold quality |
| right testis | UBERON:0004534 | 78.85 | gold quality |
| testis | UBERON:0000473 | 78.13 | gold quality |
| skin of leg | UBERON:0001511 | 74.85 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 74.09 | gold quality |
| zone of skin | UBERON:0000014 | 73.00 | gold quality |
| cortical plate | UBERON:0005343 | 72.83 | gold quality |
| ventricular zone | UBERON:0003053 | 71.68 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 71.50 | gold quality |
| esophagus mucosa | UBERON:0002469 | 70.59 | gold quality |
| skin of abdomen | UBERON:0001416 | 70.41 | gold quality |
| adrenal tissue | UBERON:0018303 | 70.24 | gold quality |
| ganglionic eminence | UBERON:0004023 | 70.13 | gold quality |
| placenta | UBERON:0001987 | 69.82 | gold quality |
| islet of Langerhans | UBERON:0000006 | 67.04 | gold quality |
| stromal cell of endometrium | CL:0002255 | 65.75 | gold quality |
| prefrontal cortex | UBERON:0000451 | 65.40 | gold quality |
| superior frontal gyrus | UBERON:0002661 | 65.34 | gold quality |
| endometrium | UBERON:0001295 | 63.83 | gold quality |
| frontal cortex | UBERON:0001870 | 62.97 | gold quality |
| bone marrow cell | CL:0002092 | 62.73 | gold quality |
| rectum | UBERON:0001052 | 60.83 | gold quality |
| cerebral cortex | UBERON:0000956 | 59.94 | gold quality |
| right frontal lobe | UBERON:0002810 | 59.24 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 58.86 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 58.78 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 58.75 | gold quality |
| right adrenal gland | UBERON:0001233 | 58.65 | gold quality |
| pancreas | UBERON:0001264 | 58.31 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 0.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 0.50 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
105 targeting OTUB2, 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-7110-3P | 100.00 | 73.18 | 2486 |
| HSA-MIR-4283 | 100.00 | 66.42 | 2097 |
| HSA-MIR-574-5P | 100.00 | 66.01 | 989 |
| HSA-MIR-29A-3P | 100.00 | 73.11 | 1835 |
| HSA-MIR-29B-3P | 100.00 | 73.18 | 1833 |
| HSA-MIR-29C-3P | 100.00 | 73.15 | 1833 |
| HSA-MIR-450A-1-3P | 100.00 | 69.33 | 1837 |
| HSA-MIR-6758-5P | 100.00 | 66.21 | 1470 |
| HSA-MIR-6856-5P | 100.00 | 65.47 | 1298 |
| HSA-MIR-7152-3P | 99.97 | 67.47 | 849 |
| HSA-MIR-3688-3P | 99.97 | 72.02 | 2834 |
| HSA-MIR-1250-3P | 99.96 | 70.04 | 4038 |
| HSA-MIR-185-3P | 99.95 | 67.01 | 1743 |
| HSA-MIR-9983-3P | 99.94 | 71.48 | 3631 |
| HSA-MIR-218-5P | 99.93 | 72.22 | 2103 |
| HSA-MIR-552-5P | 99.93 | 68.56 | 1583 |
| HSA-MIR-450B-5P | 99.92 | 71.48 | 3175 |
| HSA-MIR-497-5P | 99.92 | 71.83 | 2674 |
| HSA-MIR-15A-5P | 99.90 | 72.80 | 2787 |
| HSA-MIR-15B-5P | 99.90 | 72.78 | 2798 |
| HSA-MIR-16-5P | 99.90 | 72.80 | 2780 |
| HSA-MIR-195-5P | 99.90 | 72.81 | 2805 |
| HSA-MIR-424-5P | 99.89 | 71.90 | 2641 |
| HSA-MIR-6838-5P | 99.89 | 71.94 | 2690 |
| HSA-MIR-4731-5P | 99.89 | 67.23 | 2537 |
| HSA-MIR-129-5P | 99.88 | 70.26 | 3273 |
| HSA-MIR-182-5P | 99.87 | 74.03 | 2589 |
| HSA-MIR-3065-3P | 99.87 | 70.25 | 1407 |
| HSA-MIR-4447 | 99.85 | 67.81 | 2900 |
| HSA-MIR-629-3P | 99.85 | 67.99 | 1875 |
Literature-anchored findings (GeneRIF, showing 17)
- Data report the first crystal structure of an OTU superfamily protein, otubain 2, at 2.1 A resolution and propose a model for otubain-ubiquitin binding. (PMID:15258613)
- Findings suggest that OTUB1 and OTUB2 negatively regulate virus-triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6. (PMID:19996094)
- OTUB2 is a novel promoter of viability and insulin secretion in human beta cells. OTUB2 acts through the inhibition of NF-kappaB signalling. (PMID:23515685)
- OTUB2 fine-tunes the speed of double-strand break-induced ubiquitination so that the appropriate DNA repair pathway is chosen (PMID:24560272)
- Data indicate the eubiquitinating enzyme otubain2 (OTUB2) as a regulator of GLI family zinc finger 2 (Gli2) protein degradation. (PMID:30241937)
- By elucidating a novel SUMOylation-mediated control mechanism of YAP/TAZ signaling in breast cancer metastasis, we have revealed previously unknown interplay between oncogenic KRAS and EGFR signaling and YAP/TAZ protein stability. (PMID:30472188)
- Taken together, the present study provides the first evidence that OTUB2 acts as a pivotal driver in non-small cell lung cancer tumorigenesis by stabilizing U2AF2 and activating the AKT/mTOR pathway and the Warburg effect. (PMID:30662561)
- Knockdown of otubain 2 inhibits liver cancer cell growth by suppressing NF-kappaB signaling. (PMID:32003539)
- Activation and selectivity of OTUB-1 and OTUB-2 deubiquitinylases. (PMID:32265297)
- OTUB2 promotes the progression of endometrial cancer by regulating the PKM2-mediated PI3K/AKT signaling pathway. (PMID:36316812)
- Deubiquitinase OTUB2 promotes intrahepatic cholangiocarcinoma progression by stabilizing the CTNNB1-ZEB1 axis. (PMID:36858343)
- Molecular basis for recognition and deubiquitination of 40S ribosomes by Otu2. (PMID:37169754)
- RBM15 m[6] A modification-mediated OTUB2 upregulation promotes cervical cancer progression via the AKT/mTOR signaling. (PMID:37334762)
- Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1. (PMID:38167274)
- OTUB2 silencing promotes ovarian cancer via mitochondrial metabolic reprogramming and can be synthetically targeted by CA9 inhibition. (PMID:38701117)
- Exploring the regulatory role of FBXL19-AS1 in triple-negative breast cancer through the miR-378a-3p/OTUB2 axis. (PMID:38702967)
- OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) modulates the stemness feature, chemoresistance, and epithelial-mesenchymal transition of colon cancer via regulating GINS complex subunit 1 (GINS1) expression. (PMID:39210373)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Otub2 | ENSMUSG00000021203 |
| rattus_norvegicus | Otub2 | ENSRNOG00000009117 |
| drosophila_melanogaster | CG4968 | FBGN0032214 |
| caenorhabditis_elegans | WBGENE00007718 |
Paralogs (1): OTUB1 (ENSG00000167770)
Protein
Protein identifiers
Ubiquitin thioesterase OTUB2 — Q96DC9 (reviewed: Q96DC9)
Alternative names: Deubiquitinating enzyme OTUB2, OTU domain-containing ubiquitin aldehyde-binding protein 2, Otubain-2, Ubiquitin-specific-processing protease OTUB2
All UniProt accessions (1): Q96DC9
UniProt curated annotations — full annotation on UniProt →
Function. Hydrolase that can remove conjugated ubiquitin from proteins in vitro and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Mediates deubiquitination of ‘Lys-11’-,‘Lys-48’- and ‘Lys-63’-linked polyubiquitin chains, with a preference for ‘Lys-63’-linked polyubiquitin chains.
Tissue specificity. Widely expressed. Expressed at higher level in brain.
Miscellaneous. In the structure described by PubMed:15258613, the Asp-48 active site of the catalytic triad is located too far to interact directly with the active site His-224. A possible explanation is that OTUB2 is in inactive conformation in absence of ubiquitin and a conformation change may move Asp-48 in the proximity of His-224 in presence of ubiquitin substrate.
Similarity. Belongs to the peptidase C65 family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q96DC9-1 | 1 | yes |
| Q96DC9-2 | 2 |
RefSeq proteins (1): NP_075601* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR003323 | OTU_dom | Domain |
| IPR016615 | Otubain | Family |
| IPR019400 | Peptidase_C65_otubain | Family |
| IPR038765 | Papain-like_cys_pep_sf | Homologous_superfamily |
| IPR042467 | Peptidase_C65_otubain_sub2 | Homologous_superfamily |
| IPR042468 | Peptidase_C65_otubain_sub1 | Homologous_superfamily |
Pfam: PF10275
UniProt features (30 total): helix 10, strand 8, active site 3, mutagenesis site 3, turn 2, chain 1, domain 1, site 1, splice variant 1
Structure
Experimental structures (PDB)
15 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 5QIV | X-RAY DIFFRACTION | 1.39 |
| 5QIX | X-RAY DIFFRACTION | 1.39 |
| 5QIR | X-RAY DIFFRACTION | 1.43 |
| 5QIQ | X-RAY DIFFRACTION | 1.44 |
| 5QIO | X-RAY DIFFRACTION | 1.46 |
| 5QIT | X-RAY DIFFRACTION | 1.46 |
| 5QIS | X-RAY DIFFRACTION | 1.53 |
| 5QIU | X-RAY DIFFRACTION | 1.56 |
| 5QIY | X-RAY DIFFRACTION | 1.58 |
| 5QIP | X-RAY DIFFRACTION | 1.63 |
| 5QIZ | X-RAY DIFFRACTION | 1.63 |
| 5QIW | X-RAY DIFFRACTION | 1.71 |
| 8CMS | X-RAY DIFFRACTION | 1.77 |
| 4FJV | X-RAY DIFFRACTION | 2.05 |
| 1TFF | X-RAY DIFFRACTION | 2.1 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q96DC9-F1 | 94.23 | 0.89 |
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): 48; 51 (nucleophile); 224; 226 (required to orient and stabilize the active site h-224)
Mutagenesis-validated functional residues (3):
| Position | Phenotype |
|---|---|
| 47 | affects its ability to cleave ‘k63’-linked ubiquitin. |
| 51 | loss of function in vitro. |
| 226 | abolishes deubiquitinase activity. |
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-5689896 | Ovarian tumor domain proteases |
MSigDB gene sets: 128 (showing top):
GGGACCA_MIR133A_MIR133B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GGGTGGRR_PAX4_03, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, TGANTCA_AP1_C, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_PROTEIN_K48_LINKED_DEUBIQUITINATION, TATA_C, RYTTCCTG_ETS2_B, SENESE_HDAC1_TARGETS_UP, GOBP_PROTEIN_K63_LINKED_DEUBIQUITINATION, CTGYNNCTYTAA_UNKNOWN
GO Biological Process (5): proteolysis (GO:0006508), protein deubiquitination (GO:0016579), protein K11-linked deubiquitination (GO:0035871), protein K63-linked deubiquitination (GO:0070536), protein K48-linked deubiquitination (GO:0071108)
GO Molecular Function (6): cysteine-type deubiquitinase activity (GO:0004843), ubiquitin binding (GO:0043130), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)
GO Cellular Component (1): nucleus (GO:0005634)
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 | 3 |
| protein metabolic process | 1 |
| cysteine-type deubiquitinase activity | 1 |
| protein modification by small protein removal | 1 |
| cysteine-type peptidase activity | 1 |
| deubiquitinase activity | 1 |
| ubiquitin-like protein binding | 1 |
| binding | 1 |
| hydrolase activity | 1 |
| catalytic activity, acting on a protein | 1 |
| peptidase activity | 1 |
| catalytic activity | 1 |
| intracellular membrane-bounded organelle | 1 |
Protein interactions and networks
STRING
718 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| OTUB2 | ZUP1 | Q96AP4 | 784 |
| OTUB2 | USP8 | P40818 | 705 |
| OTUB2 | OTUD5 | Q96G74 | 672 |
| OTUB2 | RNF128 | Q8TEB7 | 653 |
| OTUB2 | YOD1 | Q5VVQ6 | 650 |
| OTUB2 | OTUD1 | Q5VV17 | 636 |
| OTUB2 | OTUD6A | Q7L8S5 | 635 |
| OTUB2 | OTUD3 | Q5T2D3 | 633 |
| OTUB2 | L3MBTL1 | Q9Y468 | 631 |
| OTUB2 | UCHL3 | P15374 | 614 |
| OTUB2 | RNF168 | Q8IYW5 | 602 |
| OTUB2 | OTUD7B | Q6GQQ9 | 596 |
| OTUB2 | OTUD4 | Q01804 | 591 |
| OTUB2 | TRAF6 | Q9Y4K3 | 583 |
| OTUB2 | OTUD6B | Q8N6M0 | 577 |
| OTUB2 | ZRANB1 | Q9UGI0 | 577 |
IntAct
106 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| ARRDC3 | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.720 |
| OTUB2 | ARRDC3 | psi-mi:“MI:0915”(physical association) | 0.720 |
| OTUB2 | FAM168A | psi-mi:“MI:0915”(physical association) | 0.670 |
| TRIM54 | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.670 |
| FAM168A | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.670 |
| OTUB2 | TRIM54 | psi-mi:“MI:0915”(physical association) | 0.670 |
| OTUB2 | MID1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| REL | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| TP53BP2 | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| OTUB2 | CPSF6 | psi-mi:“MI:0915”(physical association) | 0.560 |
| SIAH1 | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| OTUB2 | LZTS2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| MID2 | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| MID1 | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| OTUB2 | REL | psi-mi:“MI:0915”(physical association) | 0.560 |
| CPSF6 | OTUB2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| OTUB2 | SIAH1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| OTUB2 | MID2 | psi-mi:“MI:0915”(physical association) | 0.560 |
BioGRID (131): OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), OTUB2 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), OTUB2 (Two-hybrid), UBC (Co-crystal Structure)
ESM2 similar proteins: A0AUR5, A8XDJ2, B0WTN3, B2RYG6, B3MCZ5, B3NRC6, B4GDM5, B4HR14, B4JW83, B4KT65, B4LJT9, B4MY75, B4P6M6, B4QFD2, P38747, P52788, P97355, Q05B57, Q0IH43, Q0V9S0, Q17D30, Q17QF2, Q292F0, Q29FC9, Q3SZA5, Q4VSI4, Q567B1, Q5ZJM3, Q6A4J8, Q6IE21, Q6NTW6, Q6NX27, Q6U7I1, Q7JVI3, Q7L8S5, Q7Q068, Q7TQI3, Q7ZV00, Q803R5, Q93009
Diamond homologs: A8XDJ2, B2RYG6, Q7TQI3, Q8LG98, Q96DC9, Q96FW1, Q9CQX0, Q9VL00, Q9XVR6
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
37 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 34 |
| Likely benign | 2 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
969 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 14:94037374:TTTCA:T | acceptor_loss | 1.0000 |
| 14:94037376:TCA:T | acceptor_loss | 1.0000 |
| 14:94037378:A:AG | acceptor_gain | 1.0000 |
| 14:94037379:G:GG | acceptor_gain | 1.0000 |
| 14:94037379:GA:G | acceptor_gain | 1.0000 |
| 14:94037379:GAGT:G | acceptor_gain | 1.0000 |
| 14:94039082:G:GG | donor_gain | 1.0000 |
| 14:94043966:TGTA:T | acceptor_loss | 1.0000 |
| 14:94043968:TA:T | acceptor_loss | 1.0000 |
| 14:94043969:A:C | acceptor_loss | 1.0000 |
| 14:94044051:ATGCT:A | donor_gain | 1.0000 |
| 14:94044053:GCT:G | donor_gain | 1.0000 |
| 14:94044056:G:GG | donor_gain | 1.0000 |
| 14:94044776:CTCAC:C | donor_gain | 1.0000 |
| 14:94044777:TCAC:T | donor_gain | 1.0000 |
| 14:94044779:AC:A | donor_gain | 1.0000 |
| 14:94044780:CG:C | donor_loss | 1.0000 |
| 14:94044781:G:GG | donor_gain | 1.0000 |
| 14:94045704:T:TA | acceptor_gain | 1.0000 |
| 14:94045705:G:A | acceptor_gain | 1.0000 |
| 14:94045714:A:G | acceptor_loss | 1.0000 |
| 14:94045715:GGAA:G | acceptor_gain | 1.0000 |
| 14:94026537:TATGG:T | donor_loss | 0.9900 |
| 14:94026538:ATGGT:A | donor_loss | 0.9900 |
| 14:94026539:TGG:T | donor_loss | 0.9900 |
| 14:94026540:GGTC:G | donor_loss | 0.9900 |
| 14:94026541:G:C | donor_loss | 0.9900 |
| 14:94026542:T:A | donor_loss | 0.9900 |
| 14:94037371:A:AG | acceptor_gain | 0.9900 |
| 14:94037372:T:G | acceptor_gain | 0.9900 |
AlphaMissense
1564 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 14:94038991:G:C | R43P | 0.998 |
| 14:94039009:G:T | G49V | 0.998 |
| 14:94044688:C:A | R136S | 0.998 |
| 14:94038990:C:A | R43S | 0.997 |
| 14:94039006:A:T | D48V | 0.997 |
| 14:94044689:G:C | R136P | 0.997 |
| 14:94039009:G:A | G49E | 0.996 |
| 14:94039013:C:A | N50K | 0.996 |
| 14:94039013:C:G | N50K | 0.996 |
| 14:94039024:G:T | R54M | 0.996 |
| 14:94039025:G:C | R54S | 0.996 |
| 14:94039025:G:T | R54S | 0.996 |
| 14:94045762:C:A | A182E | 0.996 |
| 14:94045900:T:A | L228H | 0.996 |
| 14:94038978:T:C | F39L | 0.995 |
| 14:94038980:C:A | F39L | 0.995 |
| 14:94038980:C:G | F39L | 0.995 |
| 14:94044703:G:C | A141P | 0.995 |
| 14:94044739:T:C | F153L | 0.995 |
| 14:94044741:C:A | F153L | 0.995 |
| 14:94044741:C:G | F153L | 0.995 |
| 14:94044769:T:C | F163L | 0.995 |
| 14:94044771:C:A | F163L | 0.995 |
| 14:94044771:C:G | F163L | 0.995 |
| 14:94039005:G:C | D48H | 0.994 |
| 14:94039006:A:C | D48A | 0.994 |
| 14:94039008:G:T | G49W | 0.994 |
| 14:94039016:C:G | C51W | 0.994 |
| 14:94039026:G:C | A55P | 0.994 |
| 14:94045742:T:G | C175W | 0.994 |
dbSNP variants (sampled 300 via entrez): RS1000120337 (14:94034705 C>A), RS1000232721 (14:94030160 G>A), RS1000246352 (14:94039978 G>A), RS1000295939 (14:94035348 G>A), RS1000449110 (14:94035634 A>G), RS1000815814 (14:94026656 G>C), RS1000843042 (14:94039999 G>A,T), RS1000901320 (14:94034073 T>A,C), RS1001251090 (14:94045237 T>C,G), RS1001303506 (14:94045486 A>G), RS1001427009 (14:94044814 C>G,T), RS1001555725 (14:94029570 C>A), RS1001572373 (14:94035227 CCT>C), RS1001687040 (14:94034941 T>C), RS1001737080 (14:94033052 C>T)
Disease associations
OMIM: gene MIM:608338 | 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 |
|---|---|---|
| GCST90011899_20 | Aspartate aminotransferase levels | 4.000000e-10 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004736 | aspartate aminotransferase measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL4630847 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
CTD chemical–gene interactions
47 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Benzo(a)pyrene | increases methylation, affects methylation, increases expression | 4 |
| Valproic Acid | affects cotreatment, decreases expression, increases methylation | 4 |
| (+)-JQ1 compound | decreases expression | 3 |
| Tetrachlorodibenzodioxin | affects cotreatment, decreases expression, increases expression | 3 |
| Silicon Dioxide | increases expression | 2 |
| bisphenol F | affects cotreatment, increases expression | 1 |
| AKT activator SC79 | affects phosphorylation, decreases reaction | 1 |
| bisphenol A | decreases expression | 1 |
| sodium arsenate | decreases expression, increases abundance | 1 |
| benzo(e)pyrene | increases methylation | 1 |
| aflatoxin B2 | increases methylation | 1 |
| perfluorooctane sulfonic acid | decreases expression | 1 |
| CGP 52608 | increases reaction, affects binding | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | decreases expression, affects cotreatment | 1 |
| ormosil | affects binding, increases expression | 1 |
| 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide | affects cotreatment, decreases expression | 1 |
| dorsomorphin | affects cotreatment, decreases expression | 1 |
| jinfukang | affects cotreatment, increases expression | 1 |
| Temozolomide | decreases expression | 1 |
| Vorinostat | affects cotreatment, decreases expression | 1 |
| Air Pollutants | decreases expression, increases abundance | 1 |
| Arsenic | decreases expression, increases abundance | 1 |
| Cisplatin | affects cotreatment, increases expression | 1 |
| Dexamethasone | affects cotreatment, increases expression | 1 |
| Estradiol | affects cotreatment, increases expression | 1 |
| Indomethacin | affects cotreatment, increases expression | 1 |
| Lucanthone | increases expression | 1 |
| Methapyrilene | increases methylation | 1 |
| Methylcholanthrene | increases reaction, affects binding | 1 |
| Methylmercury Compounds | decreases 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 |
|---|---|---|---|
| CHEMBL4605995 | Binding | Inhibition of human GST-tagged OTUB2 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 |
Cellosaurus cell lines
2 cell lines: 2 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_TB68 | HAP1 OTUB2 (-) 1 | Cancer cell line | Male |
| CVCL_TB69 | HAP1 OTUB2 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.