NKX6-2

Chr 10

NK6 homeobox 2

Also known as: GTX, NKX6.2, NKX6B, SPAX8

NCBI Gene: 84504 ENSG00000148826 UniProt: Q9C056

This transcription factor regulates oligodendrocyte differentiation and axon-glial interactions at myelin paranodes by binding to MBP and PLP1 promoter regions. Biallelic mutations cause spastic ataxia 8, an autosomal recessive disorder characterized by hypomyelinating leukodystrophy. The pathogenic mechanism involves disrupted myelination due to impaired transcriptional regulation of key myelin proteins.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; regulation of DNA-templated transcription; and regulation of myelination. Predicted to act upstream of or within several processes, including central nervous system myelination; pancreatic A cell differentiation; and regulation of oligodendrocyte differentiation. Predicted to be located in chromatin. Predicted to be active in nucleus. Implicated in spastic ataxia 8. [provided by Alliance of Genome Resources, Apr 2025]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy

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

1.31

LOEUF

LOF

Mechanism· G2P

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GeneReview available — NKX6-2