TMSB4Y

Chr Y

thymosin beta 4 Y-linked

Also known as: TB4Y

NCBI Gene: 9087 ENSG00000154620 UniProt: O14604 OMIM: 400017

This gene encodes an actin-sequestering protein that binds actin monomers and inhibits actin polymerization, playing an important role in cytoskeletal organization. TMSB4Y is located in the male-specific region of the Y chromosome and has a homolog on the X chromosome that escapes X-inactivation. No established disease associations have been reported for mutations in this gene.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.86

Clinical Summary— TMSB4Y

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

4 total variants — no pathogenic classifications of 4 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.86LOEUF

pLI 0.319

Z-score 0.55

OE 0.00 (0.00–1.86)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.50Z-score

OE missense 1.64 (0.88–1.95)

8 obs / 4.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.86)

0≤0.351.4

Missense OE?1.64 (0.88–1.95)

0≤0.61.4

Synonymous OE?2.11

0≤1.21.6

LoF obs/exp: 0 / 0.4Missense obs/exp: 8 / 4.9Syn Z: -0.85

This gene — mechanism propensity

0.4289th %ile

GOF

0.6735th %ile

LOF

0.2678th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

4 submitted variants in ClinVar

ClinVar

Classification Summary

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous
Pathogenic	—	—	—	—
Likely Pathogenic	—	—	—	—
VUS	—	—	—	—
Likely Benign	—	—	—	—
Benign	—	—	—	—
Total	—

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

60 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap TMSB4Y — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →