NKX1-1

Chr 4

NK1 homeobox 1

Also known as: HSPX153, NKX-1.1, SAX2

NCBI Gene: 54729 ENSG00000235608 UniProt: Q15270 OMIM: 617869

The protein is a transcription factor that regulates genes involved in energy homeostasis, with expression predominantly in the brainstem near serotonergic neurons. Mutations cause a severe neurodevelopmental disorder characterized by early-onset failure to thrive, lack of subcutaneous fat, and early lethality, following an autosomal recessive inheritance pattern. The gene shows moderate constraint against loss-of-function variants (pLI 0.71, LOEUF 0.72).

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a transcription factor that belongs to NKX family of homeodomain-containing proteins which are critical regulators of organ development. In mice, the orthologous gene is expressed predominantly in the brainstem, in the vicinity of serotonergic neurons, and is required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis. Mice with a knockout of the orthologous gene lack subcutaneous fat and intra-abdominal epididymal and mesenteric white adipose tissue two weeks after birth, and die within three weeks after birth. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.72

LOEUF

LOF

Mechanism· predicted