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9 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ADAM18
ADAM metallopeptidase domain 18
Chromosome 8 · 8p11.22
NCBI Gene: 8749Ensembl: ENSG00000168619.16HGNC: HGNC:196UniProt: Q0VAI3
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
metalloendopeptidase activitycell adhesionbinding of sperm to zona pellucidamale gonad developmentkidney diseasetooth diseasesystemic lupus erythematosusAbruptio Placentae
✦AI Summary

ADAM18 is a sperm surface membrane protein involved in male reproductive function. As a non-catalytic metalloprotease-like protein 1, ADAM18 is expressed exclusively or abundantly on mammalian sperm and contains a putative integrin-binding ECD motif 2, suggesting a role in oocyte recognition during fertilization. The protein is identified in the Rhesus macaque sperm proteome as one of three ADAM family members with potential functions in spermatogenesis and fertilization 1, though notably ADAM18 represents a gene subsequently lost in the human lineage 3. Despite human ADAM18 containing an uninterrupted open reading frame and producing mature protein on human sperm 2, its functional significance in human reproduction remains incompletely characterized. Beyond reproductive contexts, ADAM18 has been identified as a component of matrix metalloproteinase-related prognostic signatures in hepatocellular carcinoma 4 and as a novel biomarker in diabetic retinopathy pathogenesis 5, suggesting broader roles in disease-relevant proteolytic and inflammatory processes. Additionally, ADAM18 mutations have been identified in uterine leiomyomas, implicating it in cell-to-cell interactions and extracellular matrix remodeling 6. The protein is significantly downregulated in fetal growth restriction contexts, indicating involvement in prenatal brain development 7.

Sources cited
1
ADAM18 is a sperm proteome component with non-catalytic metalloprotease-like function, part of three macaque sperm ADAMs with roles in spermatogenesis and fertilization
PMID: 23816990
2
Human ADAM18 (tMDC III) is expressed on sperm, contains an uninterrupted open reading frame, produces mature protein, and has a putative integrin-binding ECD motif for oolemma binding
PMID: 12200459
3
ADAM18 represents a reproductive ADAM gene subsequently lost in the human lineage
PMID: 14963094
4
ADAM18 is part of a matrix metalloproteinase-related prognostic signature for hepatocellular carcinoma prognosis prediction
PMID: 38761174
5
ADAM18 was identified as a novel biomarker in diabetic retinopathy pathogenesis through protein-metabolite interactome analysis
PMID: 33520806
6
ADAM18 mutations were identified in uterine leiomyomas, implicating it in cell-to-cell interactions and extracellular matrix remodeling
PMID: 27889101
7
ADAM18 is significantly downregulated in fetal growth restriction contexts and is known to be involved in prenatal brain development
PMID: 23726833
Disease Associationsⓘ20
kidney diseaseOpen Targets
0.32Weak
tooth diseaseOpen Targets
0.25Weak
systemic lupus erythematosusOpen Targets
0.24Weak
Abruptio PlacentaeOpen Targets
0.24Weak
vascular diseaseOpen Targets
0.06Suggestive
amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
breast neoplasmOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
COVID-19Open Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
squamous cell carcinomaOpen Targets
0.00Suggestive
Uterine leiomyomaOpen Targets
0.00Suggestive
Sjogren syndromeOpen Targets
0.00Suggestive
metastatic neoplasmOpen Targets
0.00Suggestive
uterine fibroidOpen Targets
0.00Suggestive
clear cell renal carcinomaOpen Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
lymphomaOpen Targets
0.00Suggestive
thyroid cancer, nonmedullary, 1Open Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ADAM32Shared pathway80%ADAM2Shared pathway67%ADAM29Shared pathway60%LMLNShared pathway40%TINAGShared pathway40%ADAM30Shared pathway40%
Tissue Expression6 tissues
Heart
0%
Lung
0%
Bone Marrow
0%
Ovary
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
ADAM18ADAM32ADAM2ADAM29LMLNTINAGADAM30
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q0VAI3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.58LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.30 [1.07–1.58]
RankingsWhere ADAM18 stands among ~20K protein-coding genes
  • #16,085of 20,598
    Most Researched13
  • #15,604of 17,882
    Most Constrained (LOEUF)1.58
Genes detectedADAM18
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
Fetal growth restriction caused by MIMT1 deletion alters brain transcriptome in cattle.
PMID: 23726833
Int J Dev Neurosci · 2013
1.00
2
The Rhesus macaque (Macaca mulatta) sperm proteome.
PMID: 23816990
Mol Cell Proteomics · 2013
0.89
3
Identification of a novel matrix metalloproteinases-related prognostic signature in hepatocellular carcinoma.
PMID: 38761174
Aging (Albany NY) · 2024
0.78
4
Mechanistic dissection of diabetic retinopathy using the protein-metabolite interactome.
PMID: 33520806
J Diabetes Metab Disord · 2020
0.67
5
Highly heterogeneous genomic landscape of uterine leiomyomas by whole exome sequencing and genome-wide arrays.
PMID: 27889101
Fertil Steril · 2017
0.56