rs2277923

This is a synonymous variant in the NKX2-5 gene — it does not change the protein's amino acid sequence.

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GWAS Catalog Trait Associations (3)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

atrial fibrillation

Yuan S et al. “Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation.” Nature Communications 16(1):6426 (2025)
Allele T
OR 0.07
p 2.0e-75
N 2,584,013
Large GWAS
multi-ancestry
Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele T
OR 0.08
p 4.0e-39
N 437,772
Major Consortium StudyLarge GWAS
European

heart rate

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)
Allele T
OR 0.04
p 2.0e-49
N 425,748
Major Consortium StudyLarge GWAS
European
Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)
Allele T
OR 0.02
p 8.0e-22
N 394,642
Large GWAS
European
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ClinVar annotation

Benign★★★☆
14 submitters4 publications

Atrial septal defect 7; Cardiovascular phenotype; not specified

View on ClinVar →
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Research that mentions this SNP (1)

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Molecular Basis for Dysregulated Activation of NKX2‐5 in the Vascular Remodeling of Systemic Sclerosis
AssociationN=5,724Athina Dritsoula et al.(2018)· Arthritis &amp; Rheumatology

This study identified NKX2-5 as genetically associated with systemic sclerosis (SSc) and SSc-associated pulmonary hypertension through a meta-analysis of UK and Spanish cohorts. The rs3131917 SNP showed significant association with SSc (meta-analysis p=0.029, OR=0.91). Functional studies revealed NKX2-5 dysregulation through two regulatory mechanisms: an upstream promoter element containing rs3095870 (TEAD1 binding site) and a downstream enhancer containing rs3132139 and rs3131917.

Traits studied:Pulmonary hypertensionSystemic sclerosisVascular remodeling
PubMedDOIMetascience Observatory

About NKX2-5

This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

View all NKX2-5 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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