LMX1B

LMX1B, short for LIM homeobox transcription factor 1B, is a human gene that encodes a LIM-homeodomain transcription factor. It is located on chromosome 9q34.3 and is expressed in developing limbs, particularly the dorsal limb ectoderm, as well as in the kidney’s podocytes and other tissues. LMX1B plays a key role in limb patterning and renal development, influencing the formation and differentiation of structures in these organs.

The LMX1B protein contains two N-terminal LIM domains and a C-terminal homeobox domain, which together mediate protein interactions and DNA binding. As a transcription factor, LMX1B regulates the expression of downstream target genes involved in tissue specification, patterning, and cellular differentiation. Its activity is context-dependent, contributing to dorsal limb identity and to the proper architecture of kidney and other organ systems.

Mutations in LMX1B cause nail-patella syndrome (NPS), an autosomal dominant disorder with variable expressivity. Classic features include nail hypoplasia or aplasia, absent or hypoplastic patellae (kneecaps), elbow abnormalities, and characteristic iliac horns seen on pelvic radiographs. Renal involvement is common in NPS and can range from proteinuria to progressive renal insufficiency and failure; ocular complications, notably glaucoma, are also associated with the condition.

Diagnosis is based on clinical findings supported by genetic testing identifying pathogenic variants in LMX1B. There is no cure, so management focuses on monitoring and treating renal and ocular manifestations and addressing skeletal and nail abnormalities. Animal models, such as Lmx1b-deficient mice, have provided insights into its essential roles in limb dorsalization and kidney development.