NKX2-1

Chr 14

NK2 homeobox 1

Also known as: BCH, BHC, NK-2, NKX2.1, NKX2A, NMTC1, T/EBP, TEBP

NCBI Gene: 7080 ENSG00000136352 UniProt: P43699

This gene encodes a transcription factor that binds to the thyroglobulin promoter to regulate thyroid-specific gene expression and also controls genes involved in morphogenesis. Mutations cause autosomal dominant conditions including benign hereditary chorea, choreoathetosis with congenital hypothyroidism and neonatal respiratory distress, and nonmedullary thyroid cancer. The pathogenic mechanism involves loss of function of this critical transcriptional regulator.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtChorea, hereditary benign

UniProtChoreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction

UniProtThyroid cancer, non-medullary, 1

Clinical highlights

Gene-disease validity (ClinGen)

NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.59

LOEUF

LOF

Mechanism· G2P

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GeneReview available — NKX2-1