Variant Synonymizer: Platform to identify mutations defined in different ways is available now!

VarSy

Over 2,000 gene–disease validation summaries are now available—no login required!

Browse Summaries

TBX4 – Heritable Pulmonary Arterial Hypertension

Heritable pulmonary arterial hypertension (HPAH) is an autosomal dominant disorder with incomplete penetrance characterized by progressive pulmonary vascular obstruction and right ventricular failure. Variants in the TBX4 gene have been identified in pediatric PAH cohorts at frequencies of 10–30%, implicating TBX4 as a predisposing gene in HPAH (PMID:27770446, PMID:28877973).

Functional studies demonstrate that TBX4 variants disrupt nuclear localization and DNA-binding, leading to impaired transcriptional activation of FGF10 and abnormal lung morphogenesis in ex vivo models, consistent with pulmonary vascular pathology (PMID:35914404).

Key take-home: TBX4 testing is clinically useful for early detection and risk stratification in families with heritable PAH.

References

  • The Journal of pathology • 2017 • The role of genetics in pulmonary arterial hypertension. PMID:27770446
  • European respiratory review • 2017 • Heritable pulmonary hypertension: from bench to bedside. PMID:28877973
  • Journal of molecular and cellular cardiology • 2022 • Genetic and functional analyses of TBX4 reveal novel mechanisms underlying pulmonary arterial hypertension. PMID:35914404

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Variants in TBX4 identified in pediatric PAH cohorts (10–30% of cases) with incomplete penetrance ([PMID:27770446], [PMID:28877973])

Genetic Evidence

Limited

TBX4 variants reported in cohort studies of pediatric PAH (10–30% frequency) without segregation data

Functional Evidence

Moderate

In vitro assays show impaired TBX4-mediated FGF10 activation and ex vivo lung explant morphogenesis defects ([PMID:35914404])