NKX2-1

Protein identityUniProt · HPA

UniProt accession

P43699

Gene

NKX2-1

Ensembl

ENSG00000136352

Chromosome

14

Canonical length

371 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Golgi apparatus,Vesicles

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

371 residues, UniProt reviewed canonical sequence.

>P43699|NKX2-1
     1  MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPT AAMQQHAVGH
    61  HGAVTAAYHM TAAGVPQLSH SAVGGYCNGN LGNMSELPPY QDTMRNSASG PGWYGANPDP
   121  RFPAISRFMG PASGMNMSGM GGLGSLGDVS KNMAPLPSAP RRKRRVLFSQ AQVYELERRF
   181  KQQKYLSAPE REHLASMIHL TPTQVKIWFQ NHRYKMKRQA KDKAAQQQLQ QDSGGGGGGG
   241  GTGCPQQQQA QQQSPRRVAV PVLVKDGKPC QAGAPAPGAA SLQGHAQQQA QHQAQAAQAA
   301  AAAISVGSGG AGLGAHPGHQ PGSAGQSPDL AHHAASPAAL QGQVSSLSHL NSSGSDYGTM
   361  SCSTLLYGRT W

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NKX2-1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.69

Highest tissue expression

163 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NKX2-1.

Disease | AllUniProt

Conditions NKX2-1 is implicated in, by any mechanism.

• Chorea, hereditary benign (BHC) MIM:118700
• Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (CAHTP) MIM:610978
• Thyroid cancer, non-medullary, 1 (NMTC1) MIM:188550

Disease | GeneticClinVar

126 pathogenic / likely-pathogenic of 397 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Brain-lung-thyroid syndrome
• Benign hereditary chorea
• Inborn genetic diseases
• NKX2-1-Related Disorders
• See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.59

gnomAD pLI

0.36

gnomAD missense Z

1.81

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anatomical structure formation involved in morphogenesis
• axon guidance
• brain development
• cell differentiation
• cerebral cortex cell migration
• cerebral cortex GABAergic interneuron differentiation
• club cell differentiation
• endoderm development
• epithelial tube branching involved in lung morphogenesis
• forebrain development
• forebrain dorsal/ventral pattern formation
• forebrain neuron fate commitment
• gene expression
• globus pallidus development
• hippocampus development
• hypothalamus development
• interneuron migration
• Leydig cell differentiation
• locomotory behavior
• lung development
• lung saccule development
• negative regulation of cell migration
• negative regulation of DNA-templated transcription
• negative regulation of epithelial to mesenchymal transition
• negative regulation of transcription by RNA polymerase II
• negative regulation of transforming growth factor beta receptor signaling pathway
• oligodendrocyte differentiation
• phospholipid metabolic process
• pituitary gland development
• positive regulation of circadian rhythm
• positive regulation of DNA-templated transcription
• positive regulation of gene expression
• positive regulation of transcription by RNA polymerase II
• regulation of DNA-templated transcription
• regulation of transcription by RNA polymerase II
• response to hormone
• rhythmic process
• thyroid gland development
• type II pneumocyte differentiation
• developmental induction

Molecular functions

• DNA binding
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• enzyme binding
• intronic transcription regulatory region sequence-specific DNA binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• RNA polymerase II-specific DNA-binding transcription factor binding
• transcription cis-regulatory region binding

Cellular components

• chromatin
• nucleoplasm
• nucleus
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• Homedomain-like superfamily
• Homeobox, conserved site
• Homeodomain, metazoa
• Homeobox NK-like transcription regulators
• Homeodomain

KeywordsUniProt

• Activator
• Biological rhythms
• Congenital hypothyroidism
• DNA-binding
• Homeobox
• Nucleus
• Phosphoprotein
• Repressor
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of NKX2-1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• WWTR1
• CCDC59
• FOXA1