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27 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ADAM33
ADAM metallopeptidase domain 33
Chromosome 20 · 20p13
NCBI Gene: 80332Ensembl: ENSG00000149451.19HGNC: HGNC:15478UniProt: A2A2L3
160PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
metalloendopeptidase activityproteolysiszinc ion bindingmembraneasthmaneurodegenerative diseaseurinary system diseasebreast ductal adenocarcinoma
✦AI Summary

ADAM33 (ADAM metallopeptidase domain 33) encodes a membrane-bound metalloprotease with zinc ion binding capability that functions in proteolysis [GO annotations]. The protein exhibits metalloendopeptidase activity and is involved in extracellular matrix remodeling processes. Multiple genetic polymorphisms in ADAM33 have been extensively associated with respiratory diseases, particularly asthma and chr20 obstructive pulmonary disease (COPD). Meta-analyses demonstrate that specific ADAM33 polymorphisms, including T1 (rs2280091), V4 (rs2787094), F+1 (rs511898), and S2 (rs528557), confer increased susceptibility to asthma, with particularly strong associations observed in Asian populations 1 2 3 4. The T1 polymorphism shows robust association with childhood asthma risk in Asians 3, while the S2 and V4 variants are linked to allergic rhinitis susceptibility 5. For COPD, the S1 polymorphism increases disease risk in Asian populations 6, and the F+1 variant shows significant association with COPD susceptibility, particularly among Asians 7. Clinical validation studies in Thai populations confirm the association between ADAM33 S2 polymorphism and asthma 8. These findings suggest ADAM33 variants may serve as biomarkers for early diagnosis and risk prediction of respiratory diseases.

Sources cited
1
Meta-analysis showing T1, V4, F+1 and T+1 polymorphisms are risk factors for asthma, especially in Asian populations
PMID: 23380143
2
V4 polymorphism increases asthma risk and may serve as biomarker for early diagnosis
PMID: 25730038
3
T1 polymorphism shows significant and stable association with asthma risk in Asian children
PMID: 28285393
4
S2 polymorphism is associated with increased asthma risk in both Caucasian and Asian populations
PMID: 25068505
5
S2 and V4 polymorphisms confer susceptibility to allergic rhinitis
PMID: 26619918
6
S1 polymorphism is associated with increased COPD risk in Asian populations
PMID: 23902466
7
F+1 polymorphism increases COPD risk among Asian population
PMID: 31357020
8
Clinical validation showing S2 polymorphism association with asthma in Thai population
PMID: 31586488
Disease Associationsⓘ21
asthmaOpen Targets
0.40Weak
neurodegenerative diseaseOpen Targets
0.32Weak
urinary system diseaseOpen Targets
0.28Weak
breast ductal adenocarcinomaOpen Targets
0.11Weak
chronic obstructive pulmonary diseaseOpen Targets
0.10Suggestive
psoriasisOpen Targets
0.09Suggestive
allergic rhinitisOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
thyroid cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
cystic fibrosisOpen Targets
0.05Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.04Suggestive
histidinemiaOpen Targets
0.04Suggestive
isolated hyperchlorhidrosisOpen Targets
0.04Suggestive
colorectal cancerOpen Targets
0.03Suggestive
hyperkalemic periodic paralysisOpen Targets
0.03Suggestive
pseudohypoparathyroidism type 2Open Targets
0.03Suggestive
familial isolated hyperparathyroidismOpen Targets
0.03Suggestive
hyperparathyroidismOpen Targets
0.03Suggestive
breast neoplasmOpen Targets
0.03Suggestive
AsthmaUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PGA4Shared pathway100%PGA3Shared pathway100%CAPN14Shared pathway100%CTRB2Shared pathway100%CAPN8Shared pathway100%PRSS48Shared pathway100%
Tissue Expression6 tissues
Ovary
100%
Heart
27%
Lung
20%
Liver
4%
Bone Marrow
0%
Brain
0%
Gene Interaction Network
Click a node to explore
ADAM33PGA4PGA3CAPN14CTRB2CAPN8PRSS48
PROTEIN STRUCTURE
Preparing viewer…
PDB1R55 · 1.58 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.29LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.10 [0.94–1.29]
RankingsWhere ADAM33 stands among ~20K protein-coding genes
  • #2,801of 20,598
    Most Researched160 · top quartile
  • #13,589of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedADAM33
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
Polymorphisms of the ADAM33 gene and chronic obstructive pulmonary disease risk: a meta-analysis.
PMID: 23902466
Clin Respir J · 2014
1.00
2
A disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms and the risk of asthma: a meta-analysis.
PMID: 23380143
Hum Immunol · 2013
0.90
3
Association between V4 polymorphism in the ADAM33 gene and asthma risk: a meta-analysis.
PMID: 25730038
Genet Mol Res · 2015
0.80
4
Human ADAM33: protein maturation and localization.
PMID: 12535637
Biochem Biophys Res Commun · 2003
0.76
5
Allergic airway inflammation.
PMID: 15683615
Curr Allergy Asthma Rep · 2005
0.72