TMSB4X

Chr X

thymosin beta 4 X-linked

Also known as: FX, PTMB4, TB4X, TMSB4

NCBI Gene: 7114 ENSG00000205542 UniProt: P62328 OMIM: 300159

This protein binds and sequesters actin monomers to inhibit actin polymerization, playing an important role in cytoskeletal organization. Mutations cause X-linked intellectual disability with cardiac arrhythmias and skeletal abnormalities. The gene escapes X-inactivation and shows X-linked inheritance affecting multiple organ systems including the nervous system, heart, and skeletal development.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.67

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.67LOEUF

pLI 0.412

Z-score 1.00

OE 0.00 (0.00–1.67)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.98Z-score

OE missense 0.27 (0.13–0.63)

4 obs / 14.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.67)

0≤0.351.4

Missense OE?0.27 (0.13–0.63)

0≤0.61.4

Synonymous OE?1.68

0≤1.21.6

LoF obs/exp: 0 / 1.2Missense obs/exp: 4 / 14.6Syn Z: -1.42

Background carrier burden — how many people carry a rare variant somewhere in TMSB4X?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 15,000

10 rare PASS variants

Rare truncating (LoF)

1 in 140,000

1 rare PASS variants

Rare synonymous (reference)

1 in 8,000

13 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMSB4X. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 4 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 15,000	1 in 110,000
Remaining (unassigned)	~31k	1 in 890	none seen
Admixed American	~23k	≈ 1 in 7,000	none seen
East Asian	~20k	≈ 1 in 20,000	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓