Details for: ADAM7

Gene ID: 8756

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ADAM7

Ensembl ID: ENSG00000069206

Description: ADAM metallopeptidase domain 7

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • retinal ganglion cell CL0000740
    CSI 1.78
    rCSI 3.92%
    PRS 93.46
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.69
    rCSI 2.47%
    PRS 92.45
  • ON parasol ganglion cell CL4033052
    CSI 0.52
    rCSI 7.37%
    PRS 93.61
  • ON midget ganglion cell CL4033046
    CSI 0.42
    rCSI 8.58%
    PRS 93.38
  • OFF midget ganglion cell CL4033047
    CSI 0.31
    rCSI 6.25%
    PRS 93.55

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [ADAM7](/details-gene/8756) is a protein-coding gene located on chromosome 8p21.2 that encodes a member of the ADAM (a disintegrin and metalloproteinase) family of transmembrane proteins. Functionally, [ADAM7](/details-gene/8756) is characterized as a metalloendopeptidase ([GO:0004222](https://www.ebi.ac.uk/QuickGO/term/GO:0004222)) with established roles in male reproductive biology, including epididymis development ([GO:1905867](https://www.ebi.ac.uk/QuickGO/term/GO:1905867)) and the regulation of sperm motility and capacitation ([GO:1902093](https://www.ebi.ac.uk/QuickGO/term/GO:1902093), [GO:1902492](https://www.ebi.ac.uk/QuickGO/term/GO:1902492)). Despite this well-defined function in the reproductive system, transcriptomic data reveal that its most significant expression, in an **Overall** context, is found within specific neuronal populations, most notably [retinal ganglion cells](/details-cell/CL0000740). This suggests a potential, yet poorly understood, secondary role for [ADAM7](/details-gene/8756) in the central nervous system. ## Cellular Roles and Expression Landscape The expression profile of [ADAM7](/details-gene/8756) points to highly specialized roles in distinct tissue compartments. **Overall**, the gene exhibits its most significant expression signature in the nervous system. It is a particularly strong marker for [retinal ganglion cells](/details-cell/CL0000740) (CSI: 1.78), including specific subtypes such as [ON parasol ganglion cells](/details-cell/CL4033052) and [ON/OFF midget ganglion cells](/details-cell/CL4033046). Significant expression is also noted in [L5 extratelencephalic projecting glutamatergic cortical neurons](/details-cell/CL4023041) (CSI: 0.69), suggesting a role in specific long-range projection neurons of the cerebral cortex. This strong neuronal expression pattern is in striking contrast to its established functional annotation, which is exclusively linked to the male reproductive system. Its documented role as the sperm maturation-related glycoprotein GP-83 and its involvement in processes within the epididymis imply significant activity in epithelial cells of this organ. The discrepancy between the functional data, derived largely from targeted studies, and the transcriptomic data from large-scale atlases suggests that the function of [ADAM7](/details-gene/8756) may be highly context-dependent, with a previously underappreciated role in neuronal biology. ## Pathways and Molecular Function [ADAM7](/details-gene/8756) is a metalloendopeptidase that is localized to the [plasma membrane](/details-cell/GO:0005886). Its primary molecular function is proteolysis ([GO:0006508](https://www.ebi.ac.uk/QuickGO/term/GO:0006508)), the cleavage of other proteins. This enzymatic activity is central to its biological roles in the male reproductive tract, where it participates in the post-testicular maturation of sperm. Specifically, it is involved in [epididymis development](/details-cell/GO:1905867) and the positive regulation of both sperm capacitation ([GO:1902492](https://www.ebi.ac.uk/QuickGO/term/GO:1902492)) and flagellated sperm motility ([GO:1902093](https://www.ebi.ac.uk/QuickGO/term/GO:1902093)). These processes likely involve the proteolytic modification of proteins on the sperm surface or within the epididymal fluid. The mechanism by which this protease activity contributes to the biology of [retinal ganglion cells](/details-cell/CL0000740) and cortical neurons remains to be elucidated. It is plausible that, similar to other ADAM family members in the nervous system, [ADAM7](/details-gene/8756) may be involved in ectodomain shedding of cell-surface proteins, thereby modulating cell-cell signaling, adhesion, or interactions with the extracellular matrix crucial for neuronal function and maintenance. ## Research Directions The marked divergence between the established reproductive functions of [ADAM7](/details-gene/8756) and its highly specific expression pattern in the central nervous system presents a compelling area for future research. Furthermore, reports have identified mutations in [ADAM7](/details-gene/8756) in melanoma, suggesting a potential role in cancer biology ([Link](https://doi.org/10.1002/humu.21477)). Based on these observations, several testable hypotheses can be proposed: 1. Given its high expression in [retinal ganglion cells](/details-cell/CL0000740) and its metalloprotease function, [ADAM7](/details-gene/8756) may regulate synaptic plasticity or axon pathfinding in the visual system by cleaving specific cell adhesion molecules or extracellular matrix components. 2. The mutations in [ADAM7](/details-gene/8756) observed in melanoma ([Link](https://doi.org/10.1002/humu.21477)) may be loss-of-function events, suggesting that [ADAM7](/details-gene/8756) acts as a tumor suppressor by maintaining tissue integrity or regulating signaling pathways that inhibit cell proliferation and migration. To directly test the first hypothesis regarding its neuronal function, a key experiment would be to generate a conditional knockout mouse model where [ADAM7](/details-gene/8756) is specifically deleted in retinal ganglion cells. Subsequent analysis of retinal morphology, axonal projections to the superior colliculus, and visual function using techniques such as electroretinography and optical coherence tomography would clarify its role in the development and maintenance of the visual circuit. The therapeutic potential of targeting [ADAM7](/details-gene/8756) is currently speculative and depends on its precise role in disease. If the mutations in melanoma are determined to be gain-of-function, its metalloprotease activity would make it a viable target for small-molecule inhibitors. Conversely, if the mutations lead to a loss of function, indicating a tumor-suppressive role, therapeutic intervention would be more complex, possibly involving pathway-based approaches to compensate for its absence rather than direct targeting.

Genular Protein ID: 4206502130

Symbol: ADAM7_HUMAN

Name: Sperm maturation-related glycoprotein GP-83

UniProtKB Accession Codes:

Q9H2U9 A8K8X7 O75959 Q6PEJ6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 7 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 21618342

Title: Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma.

PubMed ID: 21618342

DOI: 10.1002/humu.21477

Sequence Information:

  • Length: 754
  • Mass: 85669
  • Checksum: D9E9DF9B5812B0A7
  • Sequence:
    • MLPGCIFLMI LLIPQVKEKF ILGVEGQQLV RPKKLPLIQK RDTGHTHDDD ILKTYEEELL 
YEIKLNRKTL VLHLLRSREF LGSNYSETFY SMKGEAFTRH PQIMDHCFYQ GSIVHEYDSA 
ASISTCNGLR GFFRINDQRY LIEPVKYSDE GEHLVFKYNL RVPYGANYSC TELNFTRKTV 
PGDNESEEDS KIKGIHDEKY VELFIVADDT VYRRNGHPHN KLRNRIWGMV NFVNMIYKTL 
NIHVTLVGIE IWTHEDKIEL YSNIETTLLR FSFWQEKILK TRKDFDHVVL LSGKWLYSHV 
QGISYPGGMC LPYYSTSIIK DLLPDTNIIA NRMAHQLGHN LGMQHDEFPC TCPSGKCVMD 
SDGSIPALKF SKCSQNQYHQ YLKDYKPTCM LNIPFPYNFH DFQFCGNKKL DEGEECDCGP 
AQECTNPCCD AHTCVLKPGF TCAEGECCES CQIKKAGSIC RPAKDECDFP EMCTGHSPAC 
PKDQFRVNGF PCKNSEGYCF MGKCPTREDQ CSELFDDEAI ESHDICYKMN TKGNKFGYCK 
NKENRFLPCE EKDVRCGKIY CTGGELSSLL GEDKTYHLKD PQKNATVKCK TIFLYHDSTD 
IGLVASGTKC GEGMVCNNGE CLNMEKVYIS TNCPSQCNEN PVDGHGLQCH CEEGQAPVAC 
EETLHVTNIT ILVVVLVLVI VGIGVLILLV RYRKCIKLKQ VQSPPTETLG VENKGYFGDE 
QQIRTEPILP EIHFLNKPAS KDSRGIADPN QSAK