TMSB4Y

Chr Y

thymosin beta 4 Y-linked

Also known as: TB4Y

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
60
P/LP submissions
P/LP missense
1.86
LOEUF
GOF
Mechanism· predicted
Clinical SummaryTMSB4Y
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 2 VUS of 69 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.86LOEUF
pLI 0.319
Z-score 0.55
OE 0.00 (0.001.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.50Z-score
OE missense 1.64 (0.881.95)
8 obs / 4.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.001.86)
00.351.4
Missense OE1.64 (0.881.95)
00.61.4
Synonymous OE2.11
01.21.6
LoF obs/exp: 0 / 0.4Missense obs/exp: 8 / 4.9Syn Z: -0.85
DN
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

69 submitted variants in ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic2
VUS2
Likely Benign1
Benign2
58
Pathogenic
2
Likely Pathogenic
2
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

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

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
58
Likely Pathogenic
2
VUS
2
Likely Benign
1
Benign
2
Total65

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMSB4Y · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗