Seroatlas · Human Serome Atlas

NKX2-5

Homeobox protein Nkx-2.5

Also known as: CSX, CSX1, NKX2.5, NKX25_HUMAN, NKX2E, NKX4-1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P52952
Gene
NKX2-5
Ensembl
ENSG00000183072
Chromosome
5
Canonical length
324 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors
Subcellular location
Nucleoplasm,Cytosol
Quaternary structure
Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

324 residues, UniProt reviewed canonical sequence.

>P52952|NKX2-5
     1  MFPSPALTPT PFSVKDILNL EQQQRSLAAA GELSARLEAT LAPSSCMLAA FKPEAYAGPE
    61  AAAPGLPELR AELGRAPSPA KCASAFPAAP AFYPRAYSDP DPAKDPRAEK KELCALQKAV
   121  ELEKTEADNA ERPRARRRRK PRVLFSQAQV YELERRFKQQ RYLSAPERDQ LASVLKLTST
   181  QVKIWFQNRR YKCKRQRQDQ TLELVGLPPP PPPPARRIAV PVLVRDGKPC LGDSAPYAPA
   241  YGVGLNPYGY NAYPAYPGYG GAACSPGYSC TAAYPAGPSP AQPATAAANN NFVNFGVGDL
   301  NAVQSPGIPQ SNSGVSTLHG IRAW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NKX2-5 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)
0.65
Highest tissue expression
234 nTPM

Expression across tissuesHPA

Tissue

  • heart muscle: 234 nTPM
  • spleen: 37 nTPM
  • tongue: 12 nTPM
  • blood vessel: 1.4 nTPM
  • adipose tissue: 0.7 nTPM
  • salivary gland: 0.6 nTPM

Single-cell type

  • cardiomyocytes: 20 nCPM
  • epicardial cells: 4.5 nCPM
  • breast myoepithelial cells: 2.6 nCPM
  • undifferentiated spermatogonia: 1.7 nCPM
  • myosatellite cells: 1.2 nCPM
  • differentiating spermatogonia: 1 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • cerebral cortex: 0.3 nTPM
  • midbrain: 0.3 nTPM
  • amygdala: 0.2 nTPM
  • basal ganglia: 0.2 nTPM
  • cerebellum: 0.2 nTPM
  • hippocampal formation: 0.2 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NKX2-5.

Disease | AllUniProt

Conditions NKX2-5 is implicated in, by any mechanism.

  • Atrial septal defect 7, with or without atrioventricular conduction defects (ASD7) MIM:108900
  • Tetralogy of Fallot (TOF) MIM:187500
  • Conotruncal heart malformations (CTHM) MIM:217095
  • Hypothyroidism, congenital, non-goitrous, 5 (CHNG5) MIM:225250
  • Ventricular septal defect 3 (VSD3) MIM:614432
  • Hypoplastic left heart syndrome 2 (HLHS2) MIM:614435

Disease | GeneticClinVar

128 pathogenic / likely-pathogenic of 818 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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)
0.33
gnomAD pLI
0.95
gnomAD missense Z
0.2
DepMap mean gene effect
-0.13
DepMap dependency class
selective

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of NKX2-5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads NKX2-5 as an antibody target. Whether an autoantibody or antibody against NKX2-5 could matter depends on whether native NKX2-5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NKX2-5 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

  • Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition.

Canonical record: https://seroatlas.com/gene/NKX2-5. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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