UBASH3B

Summary

UBASH3B (ubiquitin associated and SH3 domain containing B, HGNC:29884) is a protein-coding gene on chromosome 11q24.1, encoding Ubiquitin-associated and SH3 domain-containing protein B (Q8TF42). Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases.

This gene encodes a protein that contains a ubiquitin associated domain at the N-terminus, an SH3 domain, and a C-terminal domain with similarities to the catalytic motif of phosphoglycerate mutase. The encoded protein was found to inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor.

Source: NCBI Gene 84959 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 89 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_032873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29884
Approved symbol	UBASH3B
Name	ubiquitin associated and SH3 domain containing B
Location	11q24.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1959, STS-1, TULA2, TULA-2
Ensembl gene	ENSG00000154127
Ensembl biotype	protein_coding
OMIM	609201
Entrez	84959

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 retained_intron, 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000284273, ENST00000525711, ENST00000526386, ENST00000526493, ENST00000529998, ENST00000530578, ENST00000530917, ENST00000533451

RefSeq mRNA: 2 — MANE Select: NM_032873 NM_001363365, NM_032873

CCDS: CCDS31694

Canonical transcript exons

ENST00000284273 — 14 exons

Exon	Start	End
ENSE00001014157	122794702	122794834
ENSE00001014158	122798942	122799034
ENSE00001014161	122806410	122806516
ENSE00001014162	122801188	122801332
ENSE00001014168	122808067	122808176
ENSE00001014170	122796911	122797033
ENSE00001268639	122655722	122656210
ENSE00001399355	122809749	122814473
ENSE00003479909	122776219	122776272
ENSE00003493787	122783053	122783222
ENSE00003554082	122777024	122777210
ENSE00003560675	122789100	122789308
ENSE00003596886	122779497	122779695
ENSE00003603574	122796156	122796276

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 90.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5217 / max 418.5821, expressed in 1546 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117237	7.9197	1507
117255	0.3741	168
117240	0.2984	151
117239	0.2897	150
117253	0.2721	85
117238	0.0964	29
117252	0.0941	52
206480	0.0940	25
117251	0.0831	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	90.05	gold quality
cerebellum	UBERON:0002037	87.41	gold quality
cerebellar cortex	UBERON:0002129	87.07	gold quality
cerebellar hemisphere	UBERON:0002245	86.96	gold quality
cerebellar vermis	UBERON:0004720	86.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.91	gold quality
stromal cell of endometrium	CL:0002255	85.55	gold quality
decidua	UBERON:0002450	83.67	gold quality
blood	UBERON:0000178	82.38	gold quality
spleen	UBERON:0002106	82.36	gold quality
monocyte	CL:0000576	82.08	gold quality
leukocyte	CL:0000738	82.05	gold quality
bone marrow cell	CL:0002092	80.97	gold quality
bone marrow	UBERON:0002371	80.50	gold quality
placenta	UBERON:0001987	80.09	gold quality
amniotic fluid	UBERON:0000173	79.57	gold quality
substantia nigra pars compacta	UBERON:0001965	79.08	gold quality
thymus	UBERON:0002370	77.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	77.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.79	gold quality
left ventricle myocardium	UBERON:0006566	77.75	gold quality
islet of Langerhans	UBERON:0000006	77.57	gold quality
buccal mucosa cell	CL:0002336	77.28	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.02	gold quality
cortical plate	UBERON:0005343	76.74	gold quality
granulocyte	CL:0000094	76.19	gold quality
vermiform appendix	UBERON:0001154	75.75	gold quality
dorsal root ganglion	UBERON:0000044	75.44	gold quality
ventricular zone	UBERON:0003053	75.02	gold quality
upper lobe of left lung	UBERON:0008952	74.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-11	yes	174.87
E-ANND-3	yes	5.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

208 targeting UBASH3B, 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-9-5P	100.00	72.28	2361
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420

Literature-anchored findings (GeneRIF, showing 19)

• Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases (PMID:15159412)
• hsp70 inhibits apoptosis upstream and downstream of the mitochondria and is a promising therapeutic target for reversing drug-resistance in chronic myeloid leukemia-blast crisis and acute myeloid leukemia cells. (PMID:15388581)
• TULA proteins TULA and TULA-2 regulate activity of the protein tyrosine kinase Syk (PMID:18189269)
• Ablation of TULA-2 resulted in hyperphosphorylation of Syk and its downstream effector phospholipase C-gamma2 as well as enhanced GPVI-mediated platelet functional responses. (PMID:20585042)
• UBASH3B is a functional target of anti-invasive microRNA200a that is down-regulated in triple negative breast cancer. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity. (PMID:23784775)
• Data suggest that Sts1 (suppressor of T-cell receptor signaling-1) negatively regulates TCR (T-cell receptor) signaling in activated T-lymphocytes via dephosphorylation of ZAP70. (PMID:24256567)
• This recovery involves the phosphorylation of p70 independent of mTOR. (PMID:25271148)
• results demonstrate the importance of STS-1 in regulating IFN-alpha-induced autophagy in B cells (PMID:25959715)
• The study reveals a role of CBL in restricting myeloid proliferation of human AML1-ETOinduced leukemia, and identifies UBASH3B as a potential target for pharmaceutical intervention. (PMID:26449661)
• These results show that TULA-2 is a target of miR-148a-3p (PMID:26516227)
• targeting Aurora B to microtubules by UBASH3B is necessary for the timing and fidelity of chromosome segregation in human cells (PMID:26766443)
• The results show that the interaction between STS-1 and ShcA is regulated in response to EGF receptor activation. (PMID:28690151)
• UBASH3A/STS-2/TULA exhibits substantial homology to UBASH3B/STS-1/TULA-2, but possesses only a small fraction of phosphatase activity of UBASH3B/STS-1/TULA-2, and thus, its regulatory effect may be based also on the phosphatase-independent mechanisms. Critical physiologic effects of these proteins have been demonstrated in T lymphocytes, platelets, stem cells, and other important cell types. (PMID:30076707)
• the UBASH3B gene rs4936742 (T > C) polymorphism is associated with an increased risk of Behcet’s disease, especially non-ocular BD, in Iranian population. We could not find any susceptibility role of this genetic locus for posterior uveitis in Behcet’s disease. (PMID:30289285)
• Sts-1 is a negative regulator. (PMID:30962580)
• These studies help define a critical role of Ubash3b in leukemia (PMID:31399640)
• An unexpected 2-histidine phosphoesterase activity of suppressor of T-cell receptor signaling protein 1 contributes to the suppression of cell signaling. (PMID:32371395)
• Ubash3b promotes TPA-mediated suppression of leukemogenesis through accelerated downregulation of PKCdelta protein. (PMID:33556471)
• FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression. (PMID:38461240)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubash3ba	ENSDARG00000061243
danio_rerio	ubash3bb	ENSDARG00000077399
mus_musculus	Ubash3b	ENSMUSG00000032020
rattus_norvegicus	Ubash3b	ENSRNOG00000008187
drosophila_melanogaster	Epp	FBGN0039137
caenorhabditis_elegans		WBGENE00020321

Paralogs (1): UBASH3A (ENSG00000160185)

Protein

Protein identifiers

Ubiquitin-associated and SH3 domain-containing protein B — Q8TF42 (reviewed: Q8TF42)

Alternative names: Cbl-interacting protein p70, Suppressor of T-cell receptor signaling 1, T-cell ubiquitin ligand 2, Tyrosine-protein phosphatase STS1/TULA2

All UniProt accessions (1): Q8TF42

UniProt curated annotations — full annotation on UniProt →

Function. Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.

Subunit / interactions. Homodimer. Interacts with JAK2 (in vitro). Interacts with CBL. Part of a complex containing CBL and activated EGFR. Interacts with ubiquitin and with mono-ubiquitinated proteins. Interacts with ZAP70 (ubiquitinated form).

Subcellular location. Cytoplasm. Nucleus.

RefSeq proteins (2): NP_001350294, NP_116262* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR013078	His_Pase_superF_clade-1	Family
IPR015940	UBA	Domain
IPR029033	His_PPase_superfam	Homologous_superfamily
IPR035632	UBASH3B_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR051710	Phosphatase_SH3-domain	Family

Pfam: PF00300, PF14604, PF22562

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (52 total): helix 19, strand 16, turn 5, active site 3, domain 2, sequence variant 2, modified residue 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5VR6	X-RAY DIFFRACTION	1.87
8U5M	X-RAY DIFFRACTION	2.46
5W5G	X-RAY DIFFRACTION	2.48
8U7E	X-RAY DIFFRACTION	2.63
2CPW	SOLUTION NMR
2E5K	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF42-F1	85.15	0.71

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 (3): 390; 391 (tele-phosphohistidine intermediate); 576

Post-translational modifications (2): 20, 23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 327 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, GOBP_NEGATIVE_REGULATION_OF_PLATELET_ACTIVATION, GOBP_PLATELET_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_MONOATOMIC_CATION_TRANSPORT, PAX2_01, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, GOBP_CELL_CELL_ADHESION

GO Biological Process (11): negative regulation of signal transduction (GO:0009968), collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063), regulation of osteoclast differentiation (GO:0045670), negative regulation of osteoclast differentiation (GO:0045671), negative regulation of bone resorption (GO:0045779), regulation of release of sequestered calcium ion into cytosol (GO:0051279), platelet aggregation (GO:0070527), negative regulation of platelet aggregation (GO:0090331), signal transduction (GO:0007165), platelet activation (GO:0030168), collagen-activated signaling pathway (GO:0038065)

GO Molecular Function (7): protein tyrosine phosphatase activity (GO:0004725), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), phosphoprotein binding (GO:0051219), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
osteoclast differentiation	2
protein binding	2
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
collagen-activated signaling pathway	1
regulation of myeloid leukocyte differentiation	1
negative regulation of myeloid leukocyte differentiation	1
regulation of osteoclast differentiation	1
regulation of bone resorption	1
bone resorption	1
negative regulation of bone remodeling	1
release of sequestered calcium ion into cytosol	1
regulation of calcium ion transmembrane transport	1
platelet activation	1
homotypic cell-cell adhesion	1
negative regulation of platelet activation	1
negative regulation of homotypic cell-cell adhesion	1
platelet aggregation	1
regulation of platelet aggregation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell activation	1
blood coagulation	1
cell surface receptor signaling pathway	1
phosphoprotein phosphatase activity	1
ubiquitin-like protein ligase binding	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1418 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UBASH3B	ZAP70	P43403	840
UBASH3B	LCP2	Q13094	803
UBASH3B	PGAM4	Q8N0Y7	802
UBASH3B	PGAM1	P18669	797
UBASH3B	CBL	P22681	768
UBASH3B	INPPL1	O15357	681
UBASH3B	SHC1	P29353	669
UBASH3B	GRB2	P29354	614
UBASH3B	EGFR	P00533	549
UBASH3B	CCDC180	Q9P1Z9	542
UBASH3B	INPP5D	Q92835	535
UBASH3B	ABL1	P00519	513
UBASH3B	UBAC2	Q8NBM4	497
UBASH3B	CRKL	P46109	485
UBASH3B	PSMD14	O00487	477

IntAct

190 interactions, top by confidence:

A	B	Type	Score
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
TNF	TNFRSF1A	psi-mi:“MI:0914”(association)	0.960
EGFR	ERBB2	psi-mi:“MI:0914”(association)	0.950
ERRFI1	EGFR	psi-mi:“MI:0914”(association)	0.930
DOC2A	UBASH3B	psi-mi:“MI:0915”(physical association)	0.800
UBASH3B	DOC2A	psi-mi:“MI:0915”(physical association)	0.800
CBLB	UBASH3B	psi-mi:“MI:0915”(physical association)	0.780
UBASH3B	RCHY1	psi-mi:“MI:0915”(physical association)	0.780
RCHY1	UBASH3B	psi-mi:“MI:0915”(physical association)	0.780
SHC1	AP2A1	psi-mi:“MI:0914”(association)	0.730
UBASH3B	DAZAP2	psi-mi:“MI:0915”(physical association)	0.720
UBASH3B	VPS37B	psi-mi:“MI:0915”(physical association)	0.720
DAZAP2	UBASH3B	psi-mi:“MI:0915”(physical association)	0.720
VPS37B	UBASH3B	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (212): UBASH3B (Two-hybrid), UBASH3B (Two-hybrid), UBASH3B (Two-hybrid), UBASH3B (Two-hybrid), UBASH3B (Two-hybrid), UBASH3B (Two-hybrid), UBASH3B (Two-hybrid), UBASH3B (Two-hybrid), SLC25A48 (Two-hybrid), UBASH3B (Reconstituted Complex), UBASH3B (Biochemical Activity), UBASH3B (Affinity Capture-MS), UBASH3B (Affinity Capture-MS), UBASH3B (Affinity Capture-MS), UBASH3B (Two-hybrid)

ESM2 similar proteins: A1A5K6, A6H8I2, F1M386, F1PBJ0, F1QRX7, F1QWA8, F6UMY3, O02697, O14830, O97790, P26675, P48736, Q08CX5, Q21029, Q29RJ2, Q2KI13, Q3UUG6, Q3UYK3, Q3V3E1, Q5E9C4, Q5R8B7, Q5SVR0, Q5ZJX5, Q66K14, Q6DDI6, Q6DDZ9, Q6DEY8, Q6P6R7, Q6ZT07, Q7T2D0, Q8BGG7, Q8CHG7, Q8R5A6, Q8TC07, Q8TEU7, Q8TF42, Q8VCZ6, Q8WZA2, Q91WS7, Q95LL3

Diamond homologs: A4FU49, A6QLK6, A7A261, B1V8A0, E2RP94, E7F1U2, F1LRS8, G3V9M2, G5EC32, M0R4F8, O35179, O35180, O35964, O43125, O43586, O55043, O75886, O76041, O77506, O88811, O93436, P10569, P20929, P29355, P32793, P34416, P43603, P49710, P52735, P62484, P70297, P98171, Q06449, Q08012, Q0U6X7, Q13387, Q14155, Q14847, Q15811, Q2KJA1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UBASH3B	down-regulates	CBL	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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
Regulation of signaling by CBL	5	46.8×	4e-05
TNFR1-induced NF-kappa-B signaling pathway	5	31.7×	9e-05
Interleukin-3, Interleukin-5 and GM-CSF signaling	5	29.9×	9e-05
Regulation of TNFR1 signaling	6	25.4×	4e-05
Activation of NF-kappaB in B cells	5	18.6×	4e-04
Regulation of PTEN stability and activity	5	17.4×	5e-04
Signaling by ALK fusions and activated point mutants	5	14.2×	8e-04
CLEC7A (Dectin-1) signaling	5	13.5×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of epidermal growth factor receptor signaling pathway	5	53.9×	2e-05
canonical NF-kappaB signal transduction	6	31.0×	2e-05
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	17.8×	3e-04
epidermal growth factor receptor signaling pathway	5	17.4×	1e-03
ubiquitin-dependent protein catabolic process	7	7.3×	4e-03
positive regulation of canonical NF-kappaB signal transduction	7	7.2×	4e-03
protein ubiquitination	10	5.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2529 predictions. Top by Δscore:

Variant	Effect	Δscore
11:122777019:TACAG:T	acceptor_loss	1.0000
11:122777021:CAGGT:C	acceptor_loss	1.0000
11:122777022:A:AG	acceptor_gain	1.0000
11:122777022:AGGT:A	acceptor_loss	1.0000
11:122777023:G:GG	acceptor_gain	1.0000
11:122777023:GGTT:G	acceptor_gain	1.0000
11:122777023:GGTTA:G	acceptor_gain	1.0000
11:122777156:G:GT	donor_gain	1.0000
11:122777156:G:T	donor_gain	1.0000
11:122777210:GGTGA:G	donor_loss	1.0000
11:122777211:G:GC	donor_loss	1.0000
11:122777212:T:G	donor_loss	1.0000
11:122779494:CAGT:C	acceptor_loss	1.0000
11:122779495:A:AG	acceptor_gain	1.0000
11:122779496:G:GG	acceptor_gain	1.0000
11:122779496:GT:G	acceptor_gain	1.0000
11:122779496:GTGC:G	acceptor_gain	1.0000
11:122783051:A:AG	acceptor_gain	1.0000
11:122783051:AGA:A	acceptor_loss	1.0000
11:122783052:G:GA	acceptor_gain	1.0000
11:122783052:GA:G	acceptor_gain	1.0000
11:122783052:GAA:G	acceptor_gain	1.0000
11:122783052:GAAGT:G	acceptor_gain	1.0000
11:122783163:C:G	donor_gain	1.0000
11:122794700:A:AG	acceptor_gain	1.0000
11:122794701:G:GG	acceptor_gain	1.0000
11:122796151:T:TA	acceptor_gain	1.0000
11:122796153:CA:C	acceptor_loss	1.0000
11:122796154:A:AG	acceptor_gain	1.0000
11:122796154:AGCC:A	acceptor_gain	1.0000

AlphaMissense

4251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:122656191:G:T	G48W	1.000
11:122656195:T:C	F49S	1.000
11:122777034:C:G	H76D	1.000
11:122777080:T:A	V91D	1.000
11:122777083:T:C	L92P	1.000
11:122777085:T:G	Y93D	1.000
11:122777089:T:A	L94H	1.000
11:122777089:T:C	L94P	1.000
11:122777094:C:T	P96S	1.000
11:122777095:C:A	P96H	1.000
11:122777119:T:C	L104P	1.000
11:122777139:T:C	S111P	1.000
11:122777140:C:G	S111W	1.000
11:122777184:C:G	H126D	1.000
11:122777188:T:A	I127N	1.000
11:122777194:T:A	L129H	1.000
11:122777194:T:C	L129P	1.000
11:122777196:T:C	C130R	1.000
11:122777198:C:G	C130W	1.000
11:122777202:T:C	F132L	1.000
11:122777204:C:A	F132L	1.000
11:122777204:C:G	F132L	1.000
11:122779608:T:C	F172L	1.000
11:122779609:T:C	F172S	1.000
11:122779610:C:A	F172L	1.000
11:122779610:C:G	F172L	1.000
11:122779614:G:C	G174R	1.000
11:122779615:G:A	G174D	1.000
11:122779618:T:C	L175P	1.000
11:122779620:T:C	F176L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001494 (11:122675379 T>C), RS1000031034 (11:122750625 G>T), RS1000037359 (11:122757915 T>A), RS1000050593 (11:122741514 C>T), RS1000077571 (11:122678917 A>G), RS1000087768 (11:122768204 G>A), RS1000088811 (11:122744663 G>A,T), RS1000103517 (11:122810130 T>C), RS1000149521 (11:122792261 C>G), RS1000153139 (11:122708316 A>G), RS1000157313 (11:122705413 T>C), RS1000162791 (11:122658783 A>T), RS1000239831 (11:122720792 C>T), RS1000316455 (11:122700243 C>T), RS1000331442 (11:122694687 G>A)

Disease associations

OMIM: gene MIM:609201 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000755_17	HDL cholesterol	3.000000e-08
GCST000760_45	Cholesterol, total	2.000000e-10
GCST002221_44	Cholesterol, total	2.000000e-14
GCST002223_61	HDL cholesterol	1.000000e-14
GCST002896_38	Cholesterol, total	4.000000e-09
GCST002987_22	Stroke	9.000000e-07
GCST004235_70	Total cholesterol levels	5.000000e-15
GCST006503_1	Eye length	8.000000e-09
GCST006584_2	Pemphigus vulgaris	3.000000e-08
GCST006585_1818	Blood protein levels	1.000000e-11
GCST006627_95	Diastolic blood pressure	6.000000e-15
GCST007124_6	Multiple sclerosis and HDL levels (pleiotropy)	8.000000e-06
GCST007267_103	Systolic blood pressure	1.000000e-11
GCST007576_277	Chronotype	2.000000e-11
GCST008062_122	Blood urea nitrogen levels	3.000000e-08
GCST010146_28	Serum immune biomarker levels	6.000000e-09
GCST010204_185	Low density lipoprotein cholesterol levels	3.000000e-13
GCST010241_128	Apolipoprotein A1 levels	1.000000e-24
GCST010242_468	HDL cholesterol levels	7.000000e-39
GCST010245_11	LDL cholesterol levels	7.000000e-10
GCST010397_72	Gut microbiota (bacterial taxa, rank normal transformation method)	5.000000e-06
GCST011348_31	High density lipoprotein cholesterol levels	7.000000e-09
GCST90002386_365	High light scatter reticulocyte percentage of red cells	1.000000e-09
GCST90011899_5	Aspartate aminotransferase levels	1.000000e-11
GCST90013406_32	Liver enzyme levels (alkaline phosphatase)	8.000000e-11

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0004458	C-reactive protein measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007874	gut microbiome measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725045 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,752 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1697771	REBAMIPIDE	3	3,752

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10736526	UBASH3B		0.00	0

ChEMBL bioactivities

7 potent at pChembl≥5 of 7 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.24	Kd	578	nM	CHEMBL5653589
5.93	ED50	1172	nM	CHEMBL5653589
5.70	Ki	2000	nM	REBAMIPIDE
5.52	IC50	3000	nM	REBAMIPIDE
5.43	IC50	3700	nM	REBAMIPIDE

PubChem BioAssay actives

6 with measured affinity, of 35 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149706: Binding affinity to human UBASH3B incubated for 45 mins by Kinobead based pull down assay	kd	0.5780	uM
2-[(4-chlorobenzoyl)amino]-3-(2-oxo-1H-quinolin-4-yl)propanoic acid	2099342: Competitive inhibition of human STS-1 HP domain (369 to 636 residues) phosphatase activity expressed in Escherichia coli BL21 (DE3) using pNPP as substrate assessed as inhibition constant preincubated for 20 mins followed by substrate addition by Lineweaver-Burk plot analysis	ki	2.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	9
Benzo(a)pyrene	increases expression, increases methylation	5
sodium arsenite	increases abundance, increases expression, affects cotreatment	3
Aflatoxin B1	affects expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Air Pollutants	increases expression, increases abundance	2
Doxorubicin	increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	increases expression, decreases expression	2
Cyclosporine	increases expression	2
Particulate Matter	increases abundance, increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
lead acetate	increases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
1-nitropyrene	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5541097	Binding	Inhibition of human STS-1 HP domain (369 to 636 residues) phosphatase activity expressed in Escherichia coli BL21 (DE3) using pNPP as substrate preincubated for 20 mins followed by substrate addition by absorbance based spectrophotometric a	Rebamipide and Derivatives are Potent, Selective Inhibitors of Histidine Phosphatase Activity of the Suppressor of T Cell Receptor Signaling Proteins. — J Med Chem

Clinical trials (associated diseases)

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