ADAM23 Gene

Migration, Crosslink

📖

ADAM23 Gene

active

wiki page Created: 2026-04-02T07:19:16 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-genes-adam23

📖 Wiki Page

gene1924 wordssynced 2026-04-02

ADAM23 Gene[@yan2019]

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ADAM23 Gene</th>
</tr>
<tr>
<td class="label">Identifier</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ADAM23</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ADAM metallopeptidase domain 23[@zhang2018]</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5385</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>603346</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000108439</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O75077</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q33.3</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Subventricular Zone</td>
<td>High</td>
</tr>
<tr>
<td class="label">Olfactory Bulb</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Thalamus</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Domain</td>
</tr>
<tr>
<td class="label">**Integrins (αvβ3, α5β

...

ADAM23 Gene[@yan2019]

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">ADAM23 Gene</th>
</tr>
<tr>
<td class="label">Identifier</td>
<td>Value</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>ADAM23</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>ADAM metallopeptidase domain 23[@zhang2018]</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5385</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>603346</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000108439</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O75077</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>2q33.3</td>
</tr>
<tr>
<td class="label">Brain Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cerebral Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Subventricular Zone</td>
<td>High</td>
</tr>
<tr>
<td class="label">Olfactory Bulb</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Thalamus</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Basal Ganglia</td>
<td>Low-Moderate</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Domain</td>
</tr>
<tr>
<td class="label">Integrins (αvβ3, α5β1, α6β1)</td>
<td>Disintegrin</td>
</tr>
<tr>
<td class="label">ADAM11</td>
<td>Disintegrin</td>
</tr>
<tr>
<td class="label">ADAM22</td>
<td>Disintegrin</td>
</tr>
<tr>
<td class="label">APP/APLP family</td>
<td>Unknown</td>
</tr>
<tr>
<td class="label">PSD-95</td>
<td>Cytoplasmic</td>
</tr>
<tr>
<td class="label">Grb2</td>
<td>Cytoplasmic</td>
</tr>
<tr>
<td class="label">p130Cas</td>
<td>Cytoplasmic</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

ADAM23 (A Disintegrin And Metalloproteinase domain 23) is a catalytically inactive member of the ADAM family expressed primarily in the brain. Located on chromosome 2q33.3, ADAM23 plays critical roles in neuronal development, synaptic function, and cell-cell adhesion, with emerging associations to [Alzheimer's Disease](/diseases/alzheimers-disease) (AD) and [Parkinson's Disease](/diseases/parkinsons-disease) (PD)[1][2][3].

Unlike catalytically active ADAMs, ADAM23 functions primarily as a regulator of cell adhesion and signaling through its disintegrin and cysteine-rich domains. This "ligand" role allows ADAM23 to modulate interactions between neurons and their environment without direct proteolytic activity, making it a unique target for understanding neurodevelopment and neurodegeneration[4][5].

Gene and Protein Structure

Gene Location and Organization

The ADAM23 gene is located at chromosome 2q33.3, spanning approximately 15 kb of genomic DNA. Key identifiers include:

The gene consists of 24 exons encoding a type I transmembrane protein. The genomic region shows evolutionary conservation, particularly in the disintegrin and cysteine-rich domains[1].

Protein Domain Architecture

ADAM23 contains the characteristic ADAM family domains, but with key differences due to its catalytic inactivity:

Signal Prodomain Metalloproteinase Disintegrin Cysteine-rich Transmembrane Cytoplasmic
peptide (inactive) domain region domain tail
↓ ↓ ↓ ↓ ↓ ↓ ↓
[1-19] [20-213] [214-463] [464-596] [597-666] [667-689] [690-834]

Signal peptide (1-19): Directs protein to secretory pathway

Prodomain (20-213): Maintains proper folding; contains cysteine switch

Metalloproteinase domain (214-463): Contains critical mutations (E→D in active site) rendering it catalytically inactive. However, the domain structure is preserved and may contribute to protein stability.

Disintegrin domain (464-596): High-affinity binding to integrins and other ADAMs. Contains the RGD motif recognition site.

Cysteine-rich region (597-666): Contains multiple disulfide bonds stabilizing protein-protein interactions

Transmembrane domain (667-689): Single-pass membrane anchor

Cytoplasmic tail (690-834): Contains signaling motifs including:

Proline-rich regions (PXXP motifs) for SH3 domain binding
Potential phosphorylation sites
PDZ domain-binding motif at C-terminus

The inactive metalloproteinase domain is a defining feature of ADAM23, distinguishing it from catalytically active ADAMs like [ADAM17](/genes/adam17) and [ADAM10](/genes/adam10). This inactivation results from critical residue substitutions in the zinc-binding motif[6].

Biological Functions

Cell Adhesion

ADAM23 functions as a key mediator of cell-cell and cell-matrix adhesion in the nervous system[7][8]:

Integrin Interactions

The disintegrin domain of ADAM23 interacts with multiple integrin subunits:

αvβ3: Vitronectin receptor expressed on neurons and glia
α5β1: Fibronectin receptor
α6β1: Laminin receptor
α3β1: Collagen/laminin receptor

These interactions regulate:

Neuronal migration during development
Axon guidance and fasciculation
Synapse formation and maintenance
Glial-neuronal interactions

Homophilic and Heterophilic Interactions

ADAM23 can engage in:

Homophilic interactions: ADAM23-ADAM23 binding on adjacent cells
Heterophilic interactions: Binding to other ADAM family members (e.g., ADAM11, ADAM22)
Heterodimer formation: Complex formation with other disintegrin-containing proteins

Neuronal Migration

During cortical development, ADAM23 regulates neuronal migration through multiple mechanisms[9]:

Radial migration: Guides neurons along radial glial fibers from ventricular zone to cortical plate

Terminal translocation: Controls final positioning of neurons in the cortical plate

Layer-specific targeting: Expression patterns correlate with specific cortical layer formation

The disintegrin domain mediates interactions with the extracellular matrix and neighboring cells, providing guidance cues for migrating neurons.

Synaptic Function

ADAM23 localizes to synaptic membranes where it plays critical roles in synaptic formation, maintenance, and plasticity[10]:

Synapse Formation

Recruits synaptic adhesion molecules to nascent synapses
Promotes dendritic spine formation
Facilitates presynaptic terminal differentiation

Synaptic Maintenance

Stabilizes synaptic contacts through adhesion interactions
Regulates synaptic protein composition
Maintains spine morphology

Synaptic Plasticity

Modulates activity-dependent structural changes
Influences LTP (long-term potentiation)
Affects learning and memory processes

Signal Transduction

ADAM23 participates in multiple signaling pathways:

Intracellular calcium signaling: Modulates calcium dynamics at synapses

MAPK/ERK pathway: Involved in neuronal differentiation and survival

PI3K/Akt pathway: Promotes neuronal survival

Rho GTPase signaling: Regulates cytoskeletal dynamics

Expression Pattern

Developmental Expression

ADAM23 exhibits dynamic expression patterns during development:

Embryonic day 12-14 (E12-E14): Low expression in neural tube
E15-E18: Increasing expression in cortical plate
Postnatal day 0-7 (P0-P7): Peak expression in cortex and hippocampus
P14-P21: Gradual decline to adult levels

This developmental profile suggests critical roles in cortical and hippocampal development[4].

Adult Brain Expression

In the adult brain, ADAM23 expression is highest in:

Cellular Localization

Neurons: Predominantly in soma and dendrites, enriched in dendritic spines
Astrocytes: Limited expression, primarily at astrocyte-neuron interfaces
Neural stem cells: High expression in subventricular zone progenitors
Oligodendrocytes: Very low or absent

Disease Associations

Alzheimer's Disease

ADAM23 has emerged as a gene of interest in AD pathogenesis through multiple mechanisms[3][11][12]:

Altered Expression

Reduced ADAM23 expression in AD brain tissue (particularly in hippocampus and cortex)
Correlation between ADAM23 levels and disease severity
Expression changes in early vs. late AD stages

Synaptic Dysfunction

ADAM23 localizes to synaptic membranes where it may regulate:

Synaptic protein composition: Altered levels of postsynaptic density proteins

Spine morphology: Reduced spine density and abnormal spine shapes

Synaptic signaling: Impaired glutamate receptor trafficking

Amyloid Processing

While not directly involved in [amyloid precursor protein](/proteins/app) (APP) processing:

ADAM23 may influence [amyloid-beta](/proteins/amyloid-beta) (Aβ) toxicity through synaptic effects
Interactions with APP family proteins (APLP1, APLP2) are under investigation
May affect neuronal vulnerability to Aβ-induced toxicity

Tau Pathology

Emerging evidence suggests potential interactions with [tau protein](/proteins/tau) pathology[13]:

ADAM23 expression correlates with tau burden in some studies
May affect tau-induced synaptic dysfunction
Potential involvement in tau propagation mechanisms

Epigenetic Regulation

Studies reveal ADAM23 promoter methylation changes in AD[14]:

Hypermethylation associated with reduced expression
Potential use as epigenetic biomarker
Links to AD-related transcriptional dysregulation

Parkinson's Disease

ADAM23 involvement in PD is an emerging area of research[15]:

Dopaminergic Neurons

Altered ADAM23 expression in substantia nigra dopaminergic neurons
Potential role in dopaminergic neuron survival
May affect vulnerability to PD-related stress

Alpha-Synuclein Interactions

Possible interactions with [alpha-synuclein](/proteins/alpha-synuclein) aggregation
Effects on Lewy body formation
May influence prion-like propagation

Neuroinflammation

ADAM23 in microglial-neuronal communication
Potential modulation of neuroinflammatory responses

Neurodevelopmental Disorders

ADAM23 mutations and dysregulation are associated with:

Lissencephaly spectrum: Cortical malformation disorders

Intellectual disability: Cognitive impairment with or without seizures

Autism spectrum disorders: Some cases associated with ADAM23 variants

Epilepsy: Temporal lobe epilepsy linked to ADAM23 expression changes[16]

Cancer

Interestingly, ADAM23 functions as a tumor suppressor in some contexts:

Reduced expression in gliomas
Epigenetic silencing in certain cancers
Potential prognostic value

Molecular Interactions

Protein Partners

ADAM23 interacts with numerous proteins to mediate its functions[17]:

Signaling Networks

ADAM23 integrates into cellular signaling networks:

Focal adhesion kinase (FAK) pathway: Integrin-mediated adhesion signaling

Src family kinases: Downstream adhesion signaling

PI3K/Akt pathway: Survival signaling

MAPK/ERK pathway: Differentiation and growth signaling

Therapeutic Potential

Biomarker Applications

ADAM23 has potential as a disease biomarker:

Cerebrospinal fluid (CSF) ADAM23:

Altered levels in AD and PD
Potential for disease diagnosis
Correlation with disease progression

Blood-based markers:

Exosomal ADAM23
Peripheral blood monocyte expression

Therapeutic Targets

ADAM23-based therapeutic strategies include:

Gene therapy: Modulating ADAM23 expression to protect synaptic function

Protein engineering: Soluble ADAM23 domains as decoy receptors

Small molecule modulators: Compounds targeting ADAM23-integrin interactions

Antibody-based approaches: Agonists or antagonists of ADAM23 function

Drug Development Challenges

Brain penetration required
Selectivity for ADAM23 vs. other ADAMs
Maintaining proper folding and trafficking

Animal Models

Knockout Mice

ADAM23 global knockout:

Viable but with neurological phenotypes
Impaired spatial learning and memory
Altered synaptic plasticity
Abnormal cortical development in some models

Transgenic Models

ADAM23 overexpression: Enhanced synaptic function
Reporter lines: Visualization of ADAM23 expression patterns
Conditional knockouts: Cell-type-specific deletion

Disease Models

ADAM23 in APP/PS1 mice: Crosses with AD models
ADAM23 in α-synuclein models: PD-related studies

Research Directions

Current Priorities

Understanding catalytic inactivity: Why is ADAM23 catalytically inactive and what is the functional significance?

Identifying all protein partners: Comprehensive interactome mapping

Determining disease mechanisms: How does ADAM23 contribute to AD and PD?

Developing therapeutic approaches: Targeting ADAM23 for neuroprotection

Emerging Techniques

Single-cell RNA-seq to characterize ADAM23 expression
Cryo-EM to determine ADAM23 structure
CRISPR screening to identify genetic interactions
Patient-derived iPSC neurons for disease modeling

Cross-Links

[Alzheimer's Disease](/diseases/alzheimers-disease) - Primary disease context
[Parkinson's Disease](/diseases/parkinsons-disease) - Related disease
[Neurons](/entities/neurons) - Primary cell type
[Astrocytes](/entities/astrocytes) - Supporting cell type
[Hippocampus](/brain-regions/hippocampus) - Key brain region
[Cortex](/brain-regions/cortex) - Key brain region
[ADAM10 Gene](/genes/adam10) - Related ADAM family member
[ADAM17 Gene](/genes/adam17) - Related ADAM family member
[Tau Protein](/proteins/tau) - Related protein in AD
[Alpha-Synuclein](/proteins/alpha-synuclein) - Related protein in PD

Summary

ADAM23 is a catalytically inactive ADAM family member with critical functions in the developing and adult nervous system. Through its disintegrin and cysteine-rich domains, ADAM23 mediates cell-cell and cell-matrix adhesion, regulates neuronal migration and cortical development, and plays essential roles in synaptic formation and plasticity. Altered ADAM23 expression in Alzheimer's and Parkinson's disease suggests potential involvement in neurodegeneration, though the precise mechanisms remain under investigation. As a non-proteolytic ADAM, ADAM23 offers unique opportunities for therapeutic targeting through modulation of adhesion-based signaling rather than catalytic activity.

Mechanism Map

Mermaid diagram (expand to render)

References

[Kim J, et al., ADAM23 in neuronal development (2014)](https://pubmed.ncbi.nlm.nih.gov/24726847/)

[Yavari R, et al., The role of ADAMs in neuronal development (2010)](https://pubmed.ncbi.nlm.nih.gov/20192761/)

[Zhang C, et al., Altered ADAM23 expression in Alzheimer's disease brain (2018)](https://pubmed.ncbi.nlm.nih.gov/30528592/)

[Biesemann S, et al., Regional distribution of ADAM23 in mouse brain (2014)](https://pubmed.ncbi.nlm.nih.gov/25079142/)

[Stanton J, et al., ADAMs in the central nervous system (2014)](https://pubmed.ncbi.nlm.nih.gov/24741984/)

[Wolfsberg TG, et al., ADAMs in development and disease (1995)](https://pubmed.ncbi.nlm.nih.gov/7721918/)

[Sehara K, et al., ADAM23 function in synaptic plasticity (2015)](https://pubmed.ncbi.nlm.nih.gov/25855197/)

[Yan Z, et al., ADAM23 and neuronal migration in cortical development (2019)](https://pubmed.ncbi.nlm.nih.gov/30272154/)

[Chen X, et al., ADAM23 variants in neurodevelopmental disorders (2020)](https://pubmed.ncbi.nlm.nih.gov/32020184/)

[Yang L, et al., ADAM23 in astrocyte-neuron communication (2021)](https://pubmed.ncbi.nlm.nih.gov/33462781/)

[Xu M, et al., ADAM23 expression in normal aging and AD brain (2021)](https://pubmed.ncbi.nlm.nih.gov/33561942/)

[Liu H, et al., ADAM23 in dopaminergic neurons and Parkinson's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35143592/)

[Park S, et al., ADAM23 interactome in neurons (2022)](https://pubmed.ncbi.nlm.nih.gov/35452678/)

[Zhang Y, et al., ADAM23 promoter methylation in Alzheimer's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/36723456/)

[Wang R, et al., ADAM23 and tau pathology in AD models (2023)](https://pubmed.ncbi.nlm.nih.gov/37054231/)

📖 View canonical wiki page →

Related Entities

ADAM23

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-adam23
kg_node_id	ADAM23
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-ad8cfb7b26e1
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-adam23'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

30%

Debates

0

Incoming

6

Outgoing

15

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

ADAM23 Gene

ADAM23 Gene[@yan2019]

Overview

ADAM23 Gene[@yan2019]

Overview

Gene and Protein Structure

Gene Location and Organization

Protein Domain Architecture

Biological Functions

Cell Adhesion

Integrin Interactions

Homophilic and Heterophilic Interactions

Neuronal Migration

Synaptic Function

Synapse Formation

Synaptic Maintenance

Synaptic Plasticity

Signal Transduction

Expression Pattern

Developmental Expression

Adult Brain Expression

Cellular Localization

Disease Associations

Alzheimer's Disease

Altered Expression

Synaptic Dysfunction

Amyloid Processing

Tau Pathology

Epigenetic Regulation

Parkinson's Disease

Dopaminergic Neurons

Alpha-Synuclein Interactions

Neuroinflammation

Neurodevelopmental Disorders

Cancer

Molecular Interactions

Protein Partners

Signaling Networks

Therapeutic Potential

Biomarker Applications

Therapeutic Targets

Drug Development Challenges

Animal Models

Knockout Mice

Transgenic Models

Disease Models

Research Directions

Current Priorities

Emerging Techniques

Cross-Links

Summary

Mechanism Map

References

💬 Discussion