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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SERPINA4
serpin family A member 4
Chromosome 14 · 14q32.13
NCBI Gene: 5267Ensembl: ENSG00000100665.13HGNC: HGNC:8948UniProt: A0A024R6I9
80PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular regionprotein bindingGO:0005615extracellular exosomeoptic atrophydiabetes mellitusachalasia-alacrima syndromenon-alcoholic fatty liver disease
✦AI Summary

SERPINA4 encodes kallistatin, a serine protease inhibitor that functions as an anti-inflammatory and anti-angiogenic protein. The protein primarily inhibits tissue kallikrein activity through formation of stable enzyme-inhibitor complexes [UniProt]. SERPINA4 demonstrates protective roles in multiple disease contexts. In cardiovascular disease, kallistatin shows anti-inflammatory properties and correlates with abdominal aortic aneurysm pathogenesis, where decreased levels represent increased rupture risk 1. The protein also functions as a potential biomarker for organ dysfunction - reduced plasma levels correlate with chr14 liver disease severity 2, while urinary SERPINA4 levels combined with other markers show diagnostic utility for diabetic kidney disease 3. Genetic variants in SERPINA4 demonstrate clinical significance across multiple conditions. The rs2093266 polymorphism associates with increased susceptibility to idiopathic nephrotic syndrome in children and correlates with steroid resistance, suggesting potential therapeutic targeting opportunities 4. This same variant, along with rs1955656 in SERPINA5, associates with severe acute kidney injury development in critically ill patients with septic shock 5. Additionally, SERPINA4 levels predict longitudinal visuospatial cognitive decline over 9-year follow-up 6. These findings establish SERPINA4 as a multifunctional protein with roles in inflammation, angiogenesis regulation, and potential clinical applications as both biomarker and therapeutic target.

Sources cited
1
SERPINA4/kallistatin shows anti-inflammatory properties in abdominal aortic aneurysm and decreased levels correlate with rupture risk
PMID: 32420091
2
Reduced plasma SERPINA4 levels correlate with chronic liver disease severity
PMID: 34528838
3
Urinary SERPINA4 levels serve as diagnostic biomarkers for diabetic kidney disease
PMID: 38299750
4
SERPINA4 rs2093266 polymorphism associates with idiopathic nephrotic syndrome susceptibility and steroid resistance in children
PMID: 40402303
5
SERPINA4 rs2093266 variant associates with severe acute kidney injury in critically ill patients with septic shock
PMID: 28270177
6
SERPINA4 levels predict longitudinal visuospatial cognitive decline over 9-year follow-up
PMID: 40469059
Disease Associationsⓘ20
optic atrophyOpen Targets
0.29Weak
diabetes mellitusOpen Targets
0.09Suggestive
achalasia-alacrima syndromeOpen Targets
0.08Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.08Suggestive
Hepatic steatosisOpen Targets
0.08Suggestive
liver dysplastic noduleOpen Targets
0.08Suggestive
cholangiocarcinomaOpen Targets
0.07Suggestive
laryngotracheoesophageal cleftOpen Targets
0.06Suggestive
age-related macular degenerationOpen Targets
0.06Suggestive
esophageal adenocarcinomaOpen Targets
0.05Suggestive
coronary artery diseaseOpen Targets
0.05Suggestive
type 2 diabetes mellitusOpen Targets
0.05Suggestive
polycystic ovary syndromeOpen Targets
0.05Suggestive
non-alcoholic steatohepatitisOpen Targets
0.05Suggestive
Barrett's esophagusOpen Targets
0.05Suggestive
small cell lung carcinomaOpen Targets
0.04Suggestive
cardiac arrestOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
SepsisOpen Targets
0.04Suggestive
diabetic nephropathyOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KLK1Protein interaction100%KLK2Protein interaction100%PI3Protein interaction86%KLK4Protein interaction85%AZU1Protein interaction71%
Tissue Expression6 tissues
Liver
100%
Ovary
0%
Brain
0%
Heart
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SERPINA4KLK1KLK2PI3KLK4AZU1
PROTEIN STRUCTURE
Preparing viewer…
PDB6F4V · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.26LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.90 [0.65–1.26]
RankingsWhere SERPINA4 stands among ~20K protein-coding genes
  • #5,964of 20,598
    Most Researched80
  • #13,341of 17,882
    Most Constrained (LOEUF)1.26
Genes detectedSERPINA4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Association between SIRT-1 and SERPINA4 gene polymorphisms and the risk of idiopathic nephrotic syndrome among Egyptian children.
PMID: 40402303
Mol Biol Rep · 2025
1.00
2
Genetic variants in SERPINA4 and SERPINA5, but not BCL2 and SIK3 are associated with acute kidney injury in critically ill patients with septic shock.
PMID: 28270177
Crit Care · 2017
0.90
3
Quantitative ELISA for SERPINA4/kallistatin.
PMID: 34528838
Biotechniques · 2021
0.80
4
LC-MS/MS proteomics identifies plasma proteins related to cognition over 9-year follow-up.
PMID: 40469059
Alzheimers Dement · 2025
0.70
5
Screening candidate diagnostic biomarkers for diabetic kidney disease.
PMID: 38299750
J Clin Lab Anal · 2024
0.60