Molecule Information

General Information of the Molecule (ID: Mol01921)

• Name: NK2 homeobox 1 (NKX2-1) ,Homo sapiens
• Synonyms: NKX2-1; NKX2A; TITF1; TTF1
• Molecule Type: Protein
• Gene Name: NKX2-1
• Gene ID: 7080
• Location: chr14:36,516,392-36,521,149[-]
• Sequence:
  MSMSPKHTTPFSVSDILSPLEESYKKVGMEGGGLGAPLAAYRQGQAAPPTAAMQQHAVGH
  HGAVTAAYHMTAAGVPQLSHSAVGGYCNGNLGNMSELPPYQDTMRNSASGPGWYGANPDP
  RFPAISRFMGPASGMNMSGMGGLGSLGDVSKNMAPLPSAPRRKRRVLFSQAQVYELERRF
  KQQKYLSAPEREHLASMIHLTPTQVKIWFQNHRYKMKRQAKDKAAQQQLQQDSGGGGGGG
  GTGCPQQQQAQQQSPRRVAVPVLVKDGKPCQAGAPAPGAASLQGHAQQQAQHQAQAAQAA
  AAAISVGSGGAGLGAHPGHQPGSAGQSPDLAHHAASPAALQGQVSSLSHLNSSGSDYGTM
  SCSTLLYGRTW
• Function: Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differentiation phenotype. May play a role in lung development and surfactant homeostasis. Forms a regulatory loop with GRHL2 that coordinates lung epithelial cell morphogenesis and differentiation. Activates the transcription of GNRHR and plays a role in enhancing the circadian oscillation of its gene expression. Represses the transcription of the circadian transcriptional repressor NR1D1 (By similarity).
• Uniprot ID: NKX21_HUMAN
• Ensembl ID: ENSG00000136352
• HGNC ID: HGNC:11825

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Investigative Drug(s) 1 drug(s) in total

Thyrotropin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Subclinical hypothyroidism [1]

• Resistant Disease: Subclinical hypothyroidism [ICD-11: 5A00.22]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.G2626T
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality.

Disease Class: Subclinical hypothyroidism [1]

• Resistant Disease: Subclinical hypothyroidism [ICD-11: 5A00.22]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.C2519A
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality.

Disease Class: Subclinical hypothyroidism [1]

• Resistant Disease: Subclinical hypothyroidism [ICD-11: 5A00.22]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.C1302A
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality.

Disease Class: Congenital hypothyroidism [1]

• Resistant Disease: Congenital hypothyroidism [ICD-11: 5A00.0]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.G2626T
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality.

Disease Class: Congenital hypothyroidism [1]

• Resistant Disease: Congenital hypothyroidism [ICD-11: 5A00.0]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.C2519A
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality.

Disease Class: Congenital hypothyroidism [1]

• Resistant Disease: Congenital hypothyroidism [ICD-11: 5A00.0]
• Resistant Drug: Thyrotropin
• Molecule Alteration: Missense mutation; p.C1302A
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Haploinsufficiency for NKX2-1, due to either chromosomal deletions encompassing the gene locus [94] or deleterious gene mutations, produces a "brain-thyroid-lung" syndrome. The severity of the individual components of the syndrome is very variable, and includes: 1) RTSH (70% of patients), 2) "benign hereditary chorea" (90% of patients) manifesting as neonatal hypotonia preceding the development of juvenile choreoathetosis and ataxia, 3) respiratory distress (55% of patients) due to lung hypoplasia causing significantly increased mortality.

References

• Ref 1: Resistance to thyrotropin .Best Pract Res Clin Endocrinol Metab. 2017 Mar;31(2):183-194. doi: 10.1016/j.beem.2017.03.004. Epub 2017 Mar 30. 10.1016/j.beem.2017.03.004