NKX3-2

Chr 4AR

NK3 homeobox 2

Also known as: BAPX1, NKX3.2, NKX3B, SMMD

NCBI Gene: 579 ENSG00000109705 UniProt: P78367 OMIM: 602183

NKX3-2 encodes a transcriptional repressor that negatively regulates chondrocyte maturation and is required for proper middle ear development and distal stomach morphogenesis. Mutations cause spondylo-megaepiphyseal-metaphyseal dysplasia, a skeletal dysplasia inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.631).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; negative regulation of chondrocyte differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including intestinal epithelial cell development; middle ear morphogenesis; and skeletal system development. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spondylo-megaepiphyseal-metaphyseal dysplasiaMIM #613330

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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