NKX2-5 Gene - Homeobox Protein NKX2-5
Key regulator of cardiac development and congenital heart disease
Gene Information Card
| Symbol | NKX2-5 |
|---|---|
| Full Name | NK2 homeobox 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.1 |
| NCBI Gene ID | 1482 ncbi.nlm.nih.gov/gene/1482 |
| Ensembl ID | ENSG00000183072 |
| UniProt ID | P52952 |
| OMIM ID | 600584 |
| HGNC ID | 2488 |
| Aliases | CSX, NKX2.5, NKX2E, NKX4-1, cardiac-specific homeobox |
Description
NKX2-5 encodes a homeobox-containing transcription factor essential for heart development and maintenance. It regulates cardiac morphogenesis, conduction system formation, and expression of cardiac-specific genes. Mutations in NKX2-5 are associated with congenital heart defects, particularly atrial septal defects and atrioventricular conduction abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atrial septal defect (ASD) | Loss-of-function mutations impair NKX2-5 DNA binding, disrupting septal formation | ClinVar, OMIM |
| Atrioventricular block | Dominant-negative mutations interfere with transcriptional activation, causing conduction defects | ClinVar, OMIM |
| Tetralogy of Fallot | Heterozygous mutations reduce NKX2-5 activity, altering outflow tract development | ClinVar, OMIM |
| Hypoplastic left heart syndrome | Rare variants in NKX2-5 contribute to left ventricular underdevelopment | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 25.6 | High |
| Skeletal muscle | 1.2 | Low |
| Liver | 0.3 | Not detected |
| Brain | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 28.4 | High expression in differentiated cardiac cells |
| HeLa | 0.5 | Low expression |
| HEK293 | 0.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.63C>A (p.Tyr21*) | Nonsense | Rare | Loss of function; truncation of homeodomain |
| c.73C>T (p.Gln25*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.382A>G (p.Asn128Asp) | Missense | Common in ASD | Reduced DNA binding affinity |
| c.401A>G (p.Glu134Gly) | Missense | Rare | Dominant-negative effect on transcription |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein lacking homeodomain; reduced transcriptional activity.
Gain of Function (GOF)
Not reported; no activating mutations described.
Dominant Negative (DN)
Missense mutations (e.g., p.Glu134Gly) that retain DNA binding but fail to activate transcription, interfering with wild-type NKX2-5 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cardiac progenitor differentiation (Reactome R-HSA-8949215)
• Transcriptional regulation of pluripotent stem cells (WikiPathways WP3996)
Protein Summary
NKX2-5 is a 324-amino acid homeodomain transcription factor that binds DNA as a monomer or heterodimer with other cardiac factors (e.g., GATA4, TBX5). It activates genes involved in cardiac development, including ANF, MYH6, and connexin40. The protein localizes to the nucleus and is critical for septation, valve formation, and conduction system integrity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NKX2-5 Knockout HEK293 Cell Line | EDJ-KQ50218 | Human | 1482 | Details Get a Quote |
| NKX2-5 Knockout HeLa Cell Line | EDJ-KQ53020 | Human | 1482 | Details Get a Quote |
| NKX2-5 Knockout A-549 Cell Line | EDJ-KQ61484 | Human | 1482 | Details Get a Quote |
| NKX2-5 Knockout HCT 116 Cell Line | EDJ-KQ69979 | Human | 1482 | Details Get a Quote |
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