INHBA (Inhibin Subunit Beta-A / Activin A & Inhibin A Gene)
INHBA (inhibin subunit beta A; HGNC:6066, NCBI Gene ID 3624) is a human locus mapped to chromosome band 7p14.1 that encodes inhibin beta-A chain (426 aa precursor; 116 aa mature monomer forming Activin A homodimer or Inhibin A heterodimer). INHBA acts in pituitary FSH synthesis stimulation (Activin A) vs. inhibition (Inhibin A) & systemic cachexia/muscle catabolism, together with FST (Follistatin Neutralizing Protein Gene), MSTN (Myostatin Gene), and ACVR2A (Activin Receptor Type-2A Gene). Encodes the beta-A subunit that homodimerizes into Activin A (stimulating FSH and muscle catabolism) or heterodimerizes into Inhibin A.
Approved Symbol
INHBA
Chromosomal Locus
7p14.1
Encoded Product
Inhibin beta-A chain (426 aa precursor; 116 aa mature monomer forming Activin A homodimer or Inhibin A heterodimer)
Primary Pathway
Pituitary FSH synthesis stimulation (Activin A) vs. inhibition (Inhibin A) & systemic cachexia/muscle catabolism
Clinical / Therapeutic Role
Elevated circulating Activin A drives cancer cachexia, sarcopenia, heart failure & pulmonary arterial hypertension (sequestered by sotatercept)
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 2-exon gene on chromosome 7p14.1 encoding a 426-amino-acid preproprotein cleaved by furin-like proprotein convertases to liberate the 116-residue C-terminal cystine-knot mature beta-A monomer.
Cellular & Tissue Expression Profile: Expressed in ovarian granulosa and corpus luteum cells, testicular Sertoli cells, anterior pituitary gonadotropes, placental syncytiotrophoblasts, activated macrophages, senescent cells, and cachectic solid tumors.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Exhibits remarkable combinatorial duality: when two beta-A subunits disulfide-link into a homodimer, they form Activin A, a potent agonist of ACVR2A/ACVR2B-ALK4-SMAD2/3 signaling that stimulates pituitary FSH beta-subunit transcription and acts systemically alongside myostatin (MSTN) to promote muscle proteolysis and fibrosis; conversely, when one beta-A subunit heterodimerizes with an inhibin alpha subunit (INHA), it forms Inhibin A, an endocrine antagonist that binds betaglycan (TGFBR3) and ACVR2A to block Activin signaling and suppress pituitary FSH secretion.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Circulating Activin A levels rise progressively with human chronological aging, systemic inflammation, chronic kidney disease, heart failure, and cancer cachexia, where high tumor INHBA expression strongly predicts lean muscle wasting and reduced survival.
Therapeutic & Clinical Pharmacology: Neutralized endogenously by follistatin (FST) and clinically by the FDA-approved ACVR2A-Fc ligand trap sotatercept (Winrevair) in pulmonary arterial hypertension and by anti-Activin A monoclonal antibodies (garetosmab) in fibrodysplasia ossificans progressiva and cachexia trials.