TMSB4X

Summary

TMSB4X (thymosin beta 4 X-linked, HGNC:11881) is a protein-coding gene on chromosome Xp22.2, encoding Thymosin beta-4 (P62328). Plays an important role in the organization of the cytoskeleton.

This gene encodes an actin sequestering protein which plays a role in regulation of actin polymerization. The protein is also involved in cell proliferation, migration, and differentiation. This gene escapes X inactivation and has a homolog on chromosome Y.

Source: NCBI Gene 7114 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 12 total
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_021109

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11881
Approved symbol	TMSB4X
Name	thymosin beta 4 X-linked
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	TB4X
Ensembl gene	ENSG00000205542
Ensembl biotype	protein_coding
OMIM	300159
Entrez	7114

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000380633, ENST00000380635, ENST00000380636, ENST00000451311, ENST00000876159, ENST00000876160, ENST00000876161, ENST00000931312, ENST00000931313, ENST00000931314, ENST00000931315, ENST00000931316

RefSeq mRNA: 1 — MANE Select: NM_021109 NM_021109

CCDS: CCDS35202

Canonical transcript exons

ENST00000451311 — 3 exons

Exon	Start	End
ENSE00001700998	12976246	12976361
ENSE00001868926	12975110	12975168
ENSE00003844218	12976777	12977223

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.2910 / max 1529.0259, expressed in 1798 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195544	24.8518	1745
195545	8.5595	1698
195550	6.9807	1111
195549	4.9810	1156
195552	1.7787	884
195546	1.0501	652
195551	0.4725	226
195543	0.3301	169
195547	0.2865	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.99	gold quality
leukocyte	CL:0000738	99.99	gold quality
stromal cell of endometrium	CL:0002255	99.99	gold quality
ganglionic eminence	UBERON:0004023	99.99	gold quality
cortical plate	UBERON:0005343	99.99	gold quality
granulocyte	CL:0000094	99.98	gold quality
lymph node	UBERON:0000029	99.98	gold quality
gall bladder	UBERON:0002110	99.98	gold quality
blood	UBERON:0000178	99.97	gold quality
vermiform appendix	UBERON:0001154	99.97	gold quality
ascending aorta	UBERON:0001496	99.97	gold quality
right lung	UBERON:0002167	99.97	gold quality
descending thoracic aorta	UBERON:0002345	99.97	gold quality
ventricular zone	UBERON:0003053	99.97	gold quality
upper lobe of left lung	UBERON:0008952	99.97	gold quality
mucosa of stomach	UBERON:0001199	99.96	gold quality
endometrium	UBERON:0001295	99.96	gold quality
thoracic aorta	UBERON:0001515	99.96	gold quality
right coronary artery	UBERON:0001625	99.96	gold quality
left coronary artery	UBERON:0001626	99.96	gold quality
spleen	UBERON:0002106	99.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.96	gold quality
omental fat pad	UBERON:0010414	99.96	gold quality
prefrontal cortex	UBERON:0000451	99.95	gold quality
endocervix	UBERON:0000458	99.95	gold quality
rectum	UBERON:0001052	99.95	gold quality
smooth muscle tissue	UBERON:0001135	99.95	gold quality
substantia nigra	UBERON:0002038	99.95	gold quality
mucosa of transverse colon	UBERON:0004991	99.95	gold quality
body of uterus	UBERON:0009853	99.95	gold quality

Single-cell (SCXA)

Detected in 87 experiment(s), a significant marker in 40.

Experiment	Marker?	Max mean expression
E-MTAB-10432	yes	110412.57
E-MTAB-6701	yes	63597.49
E-MTAB-9221	yes	58435.10
E-CURD-112	yes	50470.91
E-MTAB-8142	yes	50146.20
E-CURD-98	yes	44633.96
E-HCAD-1	yes	43024.35
E-HCAD-24	yes	39627.42
E-HCAD-4	yes	39183.26
E-CURD-88	yes	38142.63
E-MTAB-7407	yes	38108.65
E-GEOD-125970	yes	32982.64
E-ANND-2	yes	27088.32
E-MTAB-10662	yes	26018.41
E-CURD-122	yes	25466.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ESR2

miRNA regulators (miRDB)

40 targeting TMSB4X, 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-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-605-3P	99.88	69.22	1833
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-579-3P	99.86	71.66	3628
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-3168	99.08	67.75	1384

Literature-anchored findings (GeneRIF, showing 40)

• Data show that thymosin beta4 was differentially expressed in HGF-treated HUVECs compared with control. (PMID:12163032)
• araC regulates the transcriptional level of thymosin beta4 and actin (PMID:12962156)
• in response to T beta 4 stimulation, AP-1 activity increases to enhance PAI-1 transcription through its unique AP-1-like element at -59 to -52 in the PAI-1 promoter. (PMID:14592829)
• upregulation of Tbeta-4, by promoting the disruption of cell-cell adhesion and consequential activation of the beta-catenin signaling, could be event in the acquisition of growth advantages as well as invasive phenotypes in human colorectal carcinomas (PMID:15235586)
• activated factor XIII incorporates thymosin beta(4) into the isolated gamma-module and alphaC-domain (fibrinogen A alpha); in fibrin the latter serves as the major incorporation site (PMID:15311936)
• thymosin beta4 localizes to the cell nucleus (PMID:15466884)
• Expression of thymosin beta 4 is closely related with keloid. (PMID:15698487)
• Thymosin beta4 (hTbeta4)gene was isolated and characterized. (PMID:16010977)
• PAI-1 can be bound to Tbeta4-activated endothelial cells, thus influencing their adhesive properties as well as their ability to generate plasmin (PMID:16272158)
• thymosin beta-4 increases colon carcinoma apoptosis resistance triggered by FasL and apoptosis inhibitors by downregulating Fas and upregulating Survivin expression (PMID:16364925)
• thymosin beta4 is a determinant of AdoMetDC-induced transformed phenotype and invasiveness; up-regulation of thymosin beta4 found in ras-transformed fibroblasts and metastatic human melanoma cells (PMID:16423999)
• TB4 overexpression induces paclitaxel-resistance, and therefore, TB4 could be a novel target to regulate paclitaxel-resistance. (PMID:16515784)
• In most tumors examined, cancer cells showed low or intermediate reactivity for thymosin beta4, whereas leukocytes and macrophages showed intense reactivity. (PMID:16949646)
• A search for genes upregulated by thymosin beta4 identified zyxin in SiHA cells in the presence of exogenously added thymosin beta4 and when thymosin beta4 is overexpressed using adenoviral vectors. (PMID:16956606)
• Upregulation of thymosin-beta4 mRNA and protein in conjunctival stroma and its localization in eosinophils and myofibroblasts in vernal keratoconjunctivitis(VKC) lesions. Possible role for thymosin-beta4 in tissue inflammation and remodeling in VKC. (PMID:17200658)
• Thymosin beta(4)(Ala) and thymosin beta(10) were found, but thymosin beta(10) is present in about 2.5-fold higher amounts inplatelets. (PMID:17495243)
• After abdominal surgery there is a concentration of up to 20 mg thymosin beta(4) per liter decreasing to about 1 mg/L with time. (PMID:17495244)
• The G-actin sequestering activities of all thymosin beta(4) variants correspond to their complex stabilities with G-actin (PMID:17495251)
• The localization of Oregon Green cadaverine-labeled thymosin beta(4), its fragments, and variants is investigated in a cytoplasm-depleted tumor cell line. (PMID:17567947)
• If thymosin beta4 decreases healing time, this would represent a significant advance in the treatment of pressure ulcers. (PMID:17600283)
• In both saliva and tears, concentrations of TMSB4 varied with age, which may make it an endogenous agent contributing to the rapid healing of corneal and oral wounds. (PMID:17600285)
• Our results show that hMLH1 interacts with Tbeta4 and regulates its expression and nuclear transport. (PMID:17967441)
• These data suggest that Ku80 functions as a novel receptor for Tbeta4 and mediates its intracellular activity. (PMID:17984099)
• Targeting thymosin beta 4 and related molecules may be a novel therapeutic strategy for pancreatic cancer. (PMID:18094619)
• Thymosin beta4 is a downstream molecule of stabilin-2 that plays a role in stabilin-2-mediated cell corpse clearance. (PMID:18519035)
• outlines for the first time that salivary glands during foetal life express and secrete peptides such as beta-thymosins probably involved in the development of the oral cavity and its annexes (PMID:19337364)
• study demonstrated a clear relationship between reductions in serum thymosin beta4 level and severity of hepatitis B virus-related liver failure (PMID:20128033)
• Data show a strong expression of Tbeta(4) in gut and endocrine pancreas during development. (PMID:20161756)
• colorectal cancer stem cells from different patients have higher Tbeta4 levels than normal epithelial cells (PMID:20566622)
• Data in colon cancer tissue microarray showed that thymosin beta4 and HIF-1alpha co-localized in these biopsies. (PMID:20691219)
• The TB4 could be a hypoxia responsive regulator to control tumor cell migration in angiogenesis and tumor metastasis. (PMID:20821256)
• The expression of thymosin beta4 is highly related with tumorigenesis of certain tumors including the osteosarcoma and colorectal cancers. (PMID:20975530)
• we have identified an extracellular signaling pathway where Tbeta4 increases cell surface ATP levels via ATP synthase and have shown further that ATP-responsive P2X4 receptor is required for Tbeta4-induced cell migration (PMID:21106936)
• overexpression of Tbeta4 is strongly associated with HIF-1alpha and HIF-2alpha expression and is also clinicopathologically involved with lymph node metastatic potential of breast cancer (PMID:21109953)
• Elevated expression of thymosin beta4 is associated with early-stage cervical cancers. (PMID:21213129)
• Describe beta-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. (PMID:21314931)
• Thymosin beta4 may play a role in diabetic retinal neovascularization. (PMID:21332672)
• kininogen-1 and thymosin-beta(4) are potential new biomarkers for human chronic hepatitis C. (PMID:21496200)
• findings suggest that Tbeta4 by sequestering actin prevents binding of AKT, thus inhibiting its phosphorylation (PMID:21514425)
• Tbeta4 is regulated by IL-18 and is involved in IL-18-enhanced IFN-gamma secretion in NK cells. (PMID:21742406)

Cross-species orthologs

0 orthologs

Paralogs (1): TMSB4Y (ENSG00000154620)

Protein

Protein identifiers

Thymosin beta-4 — P62328 (reviewed: P62328)

Alternative names: Fx

All UniProt accessions (2): A2VCK8, P62328

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization. Potent inhibitor of bone marrow derived stem cell differentiation. Acts by inhibits the entry of hematopoietic pluripotent stem cells into the S-phase.

Subunit / interactions. Identified in a complex composed of ACTA1, COBL, GSN AND TMSB4X. Interacts with SERPINB1.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in several hemopoietic cell lines and lymphoid malignant cells. Decreased levels in myeloma cells.

Post-translational modifications. AcSDKP is inactivated by ACE, which removes the dipeptide Lys-Pro from its C-terminus.

Induction. By alpha interferons. Decreased levels in THP-1 cells after treatment with recombinant interferon-lambda.

Similarity. Belongs to the thymosin beta family.

RefSeq proteins (1): NP_066932* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001152	Beta-thymosin	Family
IPR038386	Beta-thymosin_sf	Homologous_superfamily

Pfam: PF01290

UniProt features (24 total): modified residue 10, mutagenesis site 4, helix 3, compositionally biased region 2, initiator methionine 1, chain 1, cross-link 1, peptide 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4PL8	X-RAY DIFFRACTION	2
4PL7	X-RAY DIFFRACTION	2.3
3TU5	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62328-F1	81.14	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (11): 23, 26, 31, 32, 34, 39, 12, 2, 2, 4, 12

Mutagenesis-validated functional residues (4):

Position	Phenotype
12	very weak actin binding; no inhibition of actin polymerization.
16	binds actin 2.5-fold less than wild-type; little change in inhibition of actin polymerization.
16	very weak actin binding; no inhibition of actin polymerization.
18	very weak actin binding; no inhibition of actin polymerization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 297 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_CHEMOTAXIS, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_NEGATIVE_REGULATION_OF_STEM_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOZGIT_ESR1_TARGETS_DN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (10): actin filament organization (GO:0007015), regulation of cell migration (GO:0030334), negative regulation of actin filament polymerization (GO:0030837), tumor necrosis factor-mediated signaling pathway (GO:0033209), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of blood vessel endothelial cell migration (GO:0043536), negative regulation of inflammatory response (GO:0050728), positive regulation of endothelial cell chemotaxis (GO:2001028), positive regulation of ATP biosynthetic process (GO:2001171), positive regulation of proton-transporting ATP synthase activity, rotational mechanism (GO:1905273)

GO Molecular Function (7): RNA binding (GO:0003723), actin monomer binding (GO:0003785), actin monomer sequestering activity (GO:0003788), enzyme binding (GO:0019899), protein sequestering activity (GO:0140311), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), platelet alpha granule lumen (GO:0031093)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
positive regulation of endothelial cell migration	2
protein binding	2
actin cytoskeleton organization	1
supramolecular fiber organization	1
cell migration	1
regulation of cell motility	1
actin filament polymerization	1
regulation of actin filament polymerization	1
negative regulation of protein polymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
endothelial cell chemotaxis	1
positive regulation of chemotaxis	1
regulation of endothelial cell chemotaxis	1
ATP biosynthetic process	1
positive regulation of purine nucleotide biosynthetic process	1
positive regulation of ATP metabolic process	1
regulation of ATP biosynthetic process	1
proton-transporting ATP synthase activity, rotational mechanism	1
positive regulation of ligase activity	1
positive regulation of cation channel activity	1
nucleic acid binding	1
actin binding	1
actin monomer binding	1
protein sequestering activity	1
molecular sequestering activity	1
cytoskeletal protein binding	1
binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

100 interactions, top by confidence:

A	B	Type	Score
TMSB4X	MLH1	psi-mi:“MI:0915”(physical association)	0.730
MLH1	TMSB4X	psi-mi:“MI:0915”(physical association)	0.730
TMSB4X	MLH1	psi-mi:“MI:0403”(colocalization)	0.730
MLH1	TMSB4X	psi-mi:“MI:0403”(colocalization)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
Dctn2	DCTN6	psi-mi:“MI:0914”(association)	0.560
KRT34	TMSB4X	psi-mi:“MI:0915”(physical association)	0.560
TMSB4X	KRT31	psi-mi:“MI:0915”(physical association)	0.560
TMSB4X	FHL3	psi-mi:“MI:0915”(physical association)	0.560
KRT36	TMSB4X	psi-mi:“MI:0915”(physical association)	0.560
TMSB4X	AKAP8L	psi-mi:“MI:0915”(physical association)	0.560
TMSB4X	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
TMSB4X	UHMK1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	TMSB4X	psi-mi:“MI:0915”(physical association)	0.560
TMSB4X	COG6	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	TMSB4X	psi-mi:“MI:0915”(physical association)	0.560
APP	TMSB4X	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (91): TMSB4X (Two-hybrid), TMSB4X (Two-hybrid), TMSB4X (Two-hybrid), TMSB4X (Two-hybrid), TMSB4X (Two-hybrid), TMSB4X (Two-hybrid), TRIP6 (Two-hybrid), PNMA1 (Two-hybrid), RBPMS (Two-hybrid), KRT40 (Two-hybrid), TMSB4X (Affinity Capture-MS), TMSB4X (Affinity Capture-MS), TMSB4X (Affinity Capture-MS), TMSB4X (Affinity Capture-MS), TMSB4X (Affinity Capture-MS)

ESM2 similar proteins: A0A0K2G9F6, A0A1F5UTC9, A0A1F6CTG8, A0A1G2PK14, A0PQT4, A1TAP5, A2C4X2, A4FCI5, A6W969, A8FB65, B2GIP0, B3DVI3, B9XEI9, C4LIL0, C5DP04, C7MCY8, H5SQ95, J9ZCN8, M1YW29, O14604, O32040, O34503, P05915, P06939, P0C6M7, P12454, P20065, P24110, P29996, P34032, P62326, P62327, P62328, P62329, P76164, Q5R7H8, Q65MA1, Q6I7R5, Q6S9C5, Q7V519

Diamond homologs: O14604, P0CG34, P0CG35, P0DX04, P18758, P20065, P21752, P21753, P26351, P26352, P33248, P34032, P62326, P62327, P62328, P62329, P63312, P63313, P63314, Q5R7H8, Q6S9C5, Q6ZWY8, Q7YRC3, Q8T697, Q95274, Q9DET5, Q9DFJ9, Q9I954, Q9I955, Q9I980, Q9W7M8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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.

GO biological processes:

GO term	Partners	Fold	FDR
epithelial cell differentiation	5	14.6×	7e-03
endocytosis	7	11.1×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — DLBCLNOS, MLYM, NHL.

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

451 predictions. Top by Δscore:

Variant	Effect	Δscore
X:12976244:A:AG	acceptor_gain	1.0000
X:12976245:G:GA	acceptor_gain	1.0000
X:12976245:GC:G	acceptor_gain	1.0000
X:12976245:GCT:G	acceptor_gain	1.0000
X:12976358:GAAA:G	donor_gain	1.0000
X:12976359:A:T	donor_gain	1.0000
X:12976362:G:GG	donor_gain	1.0000
X:12976768:T:A	acceptor_gain	1.0000
X:12975287:G:GT	donor_gain	0.9900
X:12975287:G:T	donor_gain	0.9900
X:12976240:CTGCA:C	acceptor_loss	0.9900
X:12976241:TGCAG:T	acceptor_loss	0.9900
X:12976242:GCA:G	acceptor_loss	0.9900
X:12976243:CA:C	acceptor_loss	0.9900
X:12976244:A:G	acceptor_loss	0.9900
X:12976245:GCTT:G	acceptor_gain	0.9900
X:12976245:GCTTT:G	acceptor_gain	0.9900
X:12976357:AGAAA:A	donor_gain	0.9900
X:12976358:GAAAG:G	donor_gain	0.9900
X:12976360:AA:A	donor_gain	0.9900
X:12976361:AG:A	donor_loss	0.9900
X:12976362:G:GA	donor_loss	0.9900
X:12976363:T:A	donor_loss	0.9900
X:12975166:TCGG:T	donor_loss	0.9800
X:12975167:CGG:C	donor_loss	0.9800
X:12975168:GGTGA:G	donor_loss	0.9800
X:12975169:G:GG	donor_gain	0.9800
X:12975169:GTGA:G	donor_loss	0.9800
X:12975170:T:G	donor_loss	0.9800
X:12975171:GA:G	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000051382 (X:12975299 G>A), RS1001024558 (X:12973580 C>T), RS1001211869 (X:12976143 T>A,G), RS1002165220 (X:12974882 T>A), RS1002238906 (X:12974422 G>A), RS1004211352 (X:12974499 T>C), RS1004230861 (X:12973932 T>C), RS1004547973 (X:12975882 T>C), RS1004557769 (X:12975589 G>A,C), RS1005924576 (X:12977299 A>G), RS1006224444 (X:12977577 C>T), RS1007075963 (X:12977396 G>A), RS1007360318 (X:12973340 C>G), RS1009034325 (X:12975192 C>G,T), RS1010140307 (X:12976085 C>G,T)

Disease associations

OMIM: gene MIM:300159 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007798_115	Asthma	6.000000e-12
GCST007800_91	Asthma (childhood onset)	8.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067128 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.40	Kd	3996	nM	CHEMBL5653589
5.40	ED50	3996	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2149622: Binding affinity to human TMSB4X incubated for 45 mins by Kinobead based pull down assay	kd	3.9965	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression, increases acetylation	6
sodium arsenite	decreases expression, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Doxorubicin	increases activity, increases cleavage, decreases response to substance, increases expression, decreases reaction	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
4-oxoretinoic acid	increases expression	1
alpha phellandrene	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
beryllium sulfate	increases expression	1
sulindac sulfide	decreases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
cadmium acetate	increases expression	1
rutecarpine	decreases expression	1
ferrous chloride	increases expression	1
cupric oxide	decreases expression	1
bicalutamide	decreases reaction, increases expression, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
chloropicrin	increases expression	1
SC 560	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
Decitabine	affects methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652664	Binding	Binding affinity to human TMSB4X incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3JS	Abcam HEK293T TMSB4X KO	Transformed cell line	Female
CVCL_KU10	HeLa SilenciX TMSB4X	Cancer cell line	Female

Clinical trials (associated diseases)

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