TMSB4Y

Summary

TMSB4Y (thymosin beta 4 Y-linked, HGNC:11882) is a protein-coding gene on chromosome Yq11.221, encoding Thymosin beta-4, Y-chromosomal (O14604). Plays an important role in the organization of the cytoskeleton.

This gene lies within the male specific region of chromosome Y. Its homolog on chromosome X escapes X inactivation and encodes an actin sequestering protein.

Source: NCBI Gene 9087 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total
• MANE Select transcript: NM_004202

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11882
Approved symbol	TMSB4Y
Name	thymosin beta 4 Y-linked
Location	Yq11.221
Locus type	gene with protein product
Status	Approved
Aliases	TB4Y
Ensembl gene	ENSG00000154620
Ensembl biotype	protein_coding
OMIM	400017
Entrez	9087

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000284856

RefSeq mRNA: 1 — MANE Select: NM_004202 NM_004202

CCDS: CCDS14786

Canonical transcript exons

ENST00000284856 — 2 exons

Exon	Start	End
ENSE00001016870	13703899	13704435
ENSE00001274354	13705225	13706024

Expression profiles

Bgee: expression breadth ubiquitous, 112 present calls, max score 88.38.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4041 / max 21.4550, expressed in 205 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201173	0.4041	205

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.38	gold quality
corpus callosum	UBERON:0002336	80.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.09	gold quality
rectum	UBERON:0001052	77.42	gold quality
mucosa of transverse colon	UBERON:0004991	75.56	gold quality
quadriceps femoris	UBERON:0001377	71.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.56	gold quality
ventricular zone	UBERON:0003053	70.18	gold quality
prostate gland	UBERON:0002367	66.25	gold quality
metanephros cortex	UBERON:0010533	66.01	gold quality
cerebellar vermis	UBERON:0004720	65.67	gold quality
ganglionic eminence	UBERON:0004023	65.20	gold quality
putamen	UBERON:0001874	64.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	63.14	gold quality
calcaneal tendon	UBERON:0003701	62.56	gold quality
hypothalamus	UBERON:0001898	62.54	gold quality
nucleus accumbens	UBERON:0001882	61.33	gold quality
prefrontal cortex	UBERON:0000451	61.30	gold quality
substantia nigra	UBERON:0002038	61.10	gold quality
right lung	UBERON:0002167	60.85	gold quality
Ammon’s horn	UBERON:0001954	60.77	gold quality
right testis	UBERON:0004534	60.71	gold quality
testis	UBERON:0000473	60.69	gold quality
caudate nucleus	UBERON:0001873	60.65	gold quality
spinal cord	UBERON:0002240	60.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	60.62	gold quality
cerebral cortex	UBERON:0000956	60.39	gold quality
anterior cingulate cortex	UBERON:0009835	60.25	gold quality
left testis	UBERON:0004533	59.93	gold quality
thymus	UBERON:0002370	59.67	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-11	no	25.92
E-ANND-3	no	1.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting TMSB4Y, 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-4262	100.00	73.26	3931
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-196A-1-3P	99.99	72.15	2772
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-4803	99.98	71.99	3117
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-512-3P	99.97	67.35	1049
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-548M	99.70	68.87	1749

Literature-anchored findings (GeneRIF, showing 4)

• TMSB4Y has been found to encode a novel HLA-A*3303-restricted minor histocompatibility H-Y antigen, revealed during cytotoxicity assays of T cell lines from a female-to-male hemopoietic stem cell transplantation patient. (PMID:15557202)
• T beta 4 is a key activator of NK cell cytotoxicity. (PMID:19369144)
• Suggest Y chromosome gene TMSB4Y may function as a tumor suppressor gene in male breast cancer. (PMID:26702755)
• miR-183/TMSB4Y, a new potential signaling axis, involving in the progression of laryngeal cancer via modulating cell adhesion. (PMID:33356743)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tmsb4x	ENSMUSG00000049775
rattus_norvegicus	Tmsb4x	ENSRNOG00000047931

Paralogs (1): TMSB4X (ENSG00000205542)

Protein

Protein identifiers

Thymosin beta-4, Y-chromosomal — O14604 (reviewed: O14604)

All UniProt accessions (1): O14604

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.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the thymosin beta family.

RefSeq proteins (1): NP_004193* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF01290

UniProt features (4 total): compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14604-F1	80.52	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 78 (showing top): CAR_TNFRSF25, MODULE_16, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, MODULE_118, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, MUELLER_PLURINET, GOBP_ACTIN_FILAMENT_ORGANIZATION, MODULE_88, GOMF_ACTIN_BINDING, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_LENGTH, GRADE_COLON_AND_RECTAL_CANCER_UP, MODULE_104, MODULE_55, RNCTGNYNRNCTGNY_UNKNOWN

GO Biological Process (3): actin filament organization (GO:0007015), regulation of actin polymerization or depolymerization (GO:0008064), regulation of cell migration (GO:0030334)

GO Molecular Function (4): actin monomer binding (GO:0003785), protein sequestering activity (GO:0140311), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), cytoskeleton (GO:0005856), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
actin cytoskeleton organization	1
supramolecular fiber organization	1
actin polymerization or depolymerization	1
regulation of actin filament length	1
regulation of actin filament organization	1
cell migration	1
regulation of cell motility	1
actin binding	1
protein binding	1
molecular sequestering activity	1
cytoskeletal protein binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMSB4Y	USP9Y	O00507	903
TMSB4Y	KDM5D	Q9BY66	893
TMSB4Y	UTY	O14607	879
TMSB4Y	DDX3Y	O15523	865
TMSB4Y	ZFY	P08048	770
TMSB4Y	EIF1AY	O14602	740
TMSB4Y	RPS4Y1	P22090	706
TMSB4Y	PRKY	O43930	670
TMSB4Y	VCY	O14598	666
TMSB4Y	NLGN4Y	Q8NFZ3	611
TMSB4Y	AMELY	Q99218	608
TMSB4Y	BPY2	O14599	605
TMSB4Y	TBL1Y	Q9BQ87	598
TMSB4Y	RBMY1A1	P0DJD3	574
TMSB4Y	CDY2A	Q9Y6F7	572

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TMSB4Y	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
TERF1	TMSB4Y	psi-mi:“MI:0915”(physical association)	0.370
POT1	TMSB4Y	psi-mi:“MI:0915”(physical association)	0.370
EWSR1	TMSB4Y	psi-mi:“MI:0915”(physical association)	0.370
TMSB4Y	WDR46	psi-mi:“MI:0914”(association)	0.350
TERF2IP	TMSB4Y	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): TMSB4Y (Two-hybrid), DCAF13 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), LRSAM1 (Affinity Capture-MS), SAFB2 (Affinity Capture-MS), RP9 (Affinity Capture-MS), LRCH3 (Affinity Capture-MS), ZC3H13 (Affinity Capture-MS), WBP11 (Affinity Capture-MS), MYO1E (Affinity Capture-MS), DIDO1 (Affinity Capture-MS), TMSB4Y (Reconstituted Complex), SNRNP27 (Affinity Capture-MS), RBMXL1 (Affinity Capture-MS), BUD13 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G0MF47, A4IMM1, A4IMM3, A7GQV6, A7GQV9, A7Z2M2, A7Z565, A8FDQ8, A8FDQ9, A9VNW3, B7GI77, B7HAY1, B7HC95, B7I057, B7I063, B7IRQ5, B7ISF6, B7JI38, B7JI46, B9IUC1, B9IUC7, C0H3V3, C0H402, C1EN49, C1EN57, C3L9B6, C3L9C4, C3P450, C3P458, C5D5S3, C5D9Z3, G2TRU3, O14604, O31572, O31659, P71032, Q5L0A5, Q5L0A7, Q65J28, Q65J29

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

6 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	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

308 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:13704432:GAAA:G	donor_gain	1.0000
Y:13704433:A:T	donor_gain	1.0000
Y:13704436:G:GG	donor_gain	1.0000
Y:13705216:T:TA	acceptor_gain	0.9900
Y:13703931:G:GT	donor_gain	0.9800
Y:13703931:G:T	donor_gain	0.9800
Y:13704431:AGAAA:A	donor_gain	0.9800
Y:13704432:GAAAG:G	donor_gain	0.9800
Y:13704433:AAAGT:A	donor_loss	0.9800
Y:13704435:AG:A	donor_loss	0.9800
Y:13704436:GT:G	donor_loss	0.9800
Y:13704437:T:A	donor_loss	0.9800
Y:13704319:C:CA	acceptor_gain	0.9700
Y:13704434:AA:A	donor_gain	0.9600
Y:13704320:G:A	acceptor_gain	0.9500
Y:13704433:AAA:A	donor_gain	0.9500
Y:13705217:G:A	acceptor_gain	0.9500
Y:13703996:G:GT	donor_gain	0.9300
Y:13704318:AC:A	acceptor_gain	0.9300
Y:13705224:GCT:G	acceptor_gain	0.9300
Y:13705223:A:AG	acceptor_gain	0.9200
Y:13705224:G:GG	acceptor_gain	0.9200
Y:13704319:C:G	acceptor_gain	0.8900
Y:13705206:T:A	acceptor_gain	0.8900
Y:13703963:G:GT	donor_gain	0.8700
Y:13705221:GCAG:G	acceptor_loss	0.8700
Y:13705222:CA:C	acceptor_loss	0.8700
Y:13705223:AGC:A	acceptor_loss	0.8700
Y:13705224:G:GT	acceptor_loss	0.8700
Y:13704177:G:GT	donor_gain	0.8600

AlphaMissense

289 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:13704372:T:C	F13L	0.619
Y:13704374:C:A	F13L	0.619
Y:13704374:C:G	F13L	0.619

dbSNP variants (sampled 300 via entrez): RS1005517418 (Y:13704249 G>A), RS1005842717 (Y:13702167 C>T), RS1006983496 (Y:13703443 C>A,T), RS1018505160 (Y:13702234 C>G), RS1019329879 (Y:13703447 T>A), RS1021120701 (Y:13703513 A>T), RS1029840337 (Y:13702485 T>A), RS1029869279 (Y:13704946 A>G), RS1032682046 (Y:13705201 T>C), RS1039756838 (Y:13706166 G>C), RS1039998769 (Y:13704267 C>A), RS1045600241 (Y:13703805 G>C), RS1047181223 (Y:13705795 A>G), RS1048348593 (Y:13703435 C>T), RS113175306 (Y:13705628 A>T)

Disease associations

OMIM: gene MIM:400017 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Tretinoin	affects expression, increases expression	2
arsenite	decreases methylation	1
tamibarotene	affects expression	1
Air Pollutants	affects expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression, increases abundance	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D6SS	WAe001-A-2F	Embryonic stem cell	Male

Clinical trials (associated diseases)

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