Details for: ADAM23

Gene ID: 8745

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: ADAM23

Ensembl ID: ENSG00000114948

Description: ADAM metallopeptidase domain 23

Cell Significance Landscape

Associated with

Significant Cells

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

  • pvalb GABAergic cortical interneuron CL4023018
    CSI 39.39
    rCSI 49.01%
    PRS 98.45
  • VIP GABAergic cortical interneuron CL4023016
    CSI 36.86
    rCSI 44.03%
    PRS 98.66
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 33.1
    rCSI 55.56%
    PRS 98.74
  • sncg GABAergic cortical interneuron CL4023015
    CSI 31.55
    rCSI 50.74%
    PRS 98.53
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 27.28
    rCSI 48.18%
    PRS 98.67
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 24.84
    rCSI 53.88%
    PRS 97.94
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 24.03
    rCSI 58.4%
    PRS 98.07
  • rod bipolar cell CL0000751
    CSI 21.84
    rCSI 39.25%
    PRS 99.14
  • sst GABAergic cortical interneuron CL4023017
    CSI 21.44
    rCSI 27.64%
    PRS 98.94
  • retinal ganglion cell CL0000740
    CSI 20.7
    rCSI 45.73%
    PRS 98.65
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 20.57
    rCSI 49.2%
    PRS 98.24
  • retinal bipolar neuron CL0000748
    CSI 20.35
    rCSI 38.12%
    PRS 98.7
  • neuron CL0000540
    CSI 19.92
    rCSI 53.05%
    PRS 97.74
  • L6b glutamatergic cortical neuron CL4023038
    CSI 19.26
    rCSI 60.19%
    PRS 98.62
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 19.16
    rCSI 59.92%
    PRS 98.8
  • cardiac muscle cell CL0000746
    CSI 18.75
    rCSI 26.91%
    PRS 98.7
  • neural crest cell CL0011012
    CSI 18.6
    rCSI 14.7%
    PRS 99.56
  • radial glial cell CL0000681
    CSI 16.85
    rCSI 23.41%
    PRS 99.77
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 16.59
    rCSI 54.52%
    PRS 97.96
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 16.46
    rCSI 59.24%
    PRS 98.38
  • interneuron CL0000099
    CSI 16.4
    rCSI 32.92%
    PRS 99.2
  • glioblast CL0000030
    CSI 16.01
    rCSI 25.54%
    PRS 98.99
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 15.52
    rCSI 58.66%
    PRS 98.35
  • glutamatergic neuron CL0000679
    CSI 15.06
    rCSI 30.96%
    PRS 97.38
  • precursor B cell CL0000817
    CSI 15.02
    rCSI 13.16%
    PRS 99.78
  • Schwann cell CL0002573
    CSI 13.5
    rCSI 38.37%
    PRS 99.38
  • cardiac endothelial cell CL0010008
    CSI 13.33
    rCSI 53.78%
    PRS 99.82
  • inhibitory interneuron CL0000498
    CSI 13
    rCSI 30%
    PRS 98.76
  • cerebral cortex endothelial cell CL1001602
    CSI 12.82
    rCSI 22.17%
    PRS 99.13
  • vascular leptomeningeal cell CL4023051
    CSI 12.53
    rCSI 21.97%
    PRS 99.31
  • amacrine cell CL0000561
    CSI 12.51
    rCSI 36.25%
    PRS 98.8
  • neural cell CL0002319
    CSI 12.47
    rCSI 47.06%
    PRS 97.82
  • regular atrial cardiac myocyte CL0002129
    CSI 11.81
    rCSI 38.03%
    PRS 99.13
  • cerebral cortex neuron CL0010012
    CSI 11.62
    rCSI 47.35%
    PRS 98.68
  • OFFx cell CL4033036
    CSI 11.14
    rCSI 52.43%
    PRS 97.92
  • GABAergic amacrine cell CL4030027
    CSI 10.64
    rCSI 36.46%
    PRS 97.98
  • cerebellar granule cell CL0001031
    CSI 10.28
    rCSI 15.12%
    PRS 98.95
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 10.13
    rCSI 59.66%
    PRS 98.46
  • retinal cone cell CL0000573
    CSI 9.47
    rCSI 15.25%
    PRS 98.5
  • diffuse bipolar 3a cell CL4033029
    CSI 9.07
    rCSI 61.72%
    PRS 98.08
  • glycinergic amacrine cell CL4030028
    CSI 8.8
    rCSI 22.92%
    PRS 98.66
  • cardiac neuron CL0010022
    CSI 8.72
    rCSI 27.89%
    PRS 99.51
  • flat midget bipolar cell CL4033033
    CSI 8.71
    rCSI 62.24%
    PRS 97.97
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 8.07
    rCSI 14.66%
    PRS 99.01
  • diffuse bipolar 1 cell CL4033027
    CSI 7.51
    rCSI 56.47%
    PRS 97.86
  • Mueller cell CL0000636
    CSI 7.33
    rCSI 16.72%
    PRS 99.02
  • retinal rod cell CL0000604
    CSI 7.3
    rCSI 12.87%
    PRS 98.75
  • central nervous system neuron CL2000029
    CSI 7.28
    rCSI 53.52%
    PRS 98.85
  • invaginating midget bipolar cell CL4033034
    CSI 7.19
    rCSI 42.48%
    PRS 98.19
  • dopaminergic neuron CL0000700
    CSI 6.55
    rCSI 37.03%
    PRS 98.32
  • lung neuroendocrine cell CL1000223
    CSI 6.51
    rCSI 9.63%
    PRS 99.43
  • astrocyte of the cerebral cortex CL0002605
    CSI 6.47
    rCSI 14.51%
    PRS 98.77
  • medium spiny neuron CL1001474
    CSI 6.2
    rCSI 53.39%
    PRS 98.72
  • Bergmann glial cell CL0000644
    CSI 5.54
    rCSI 7.58%
    PRS 99
  • glial cell CL0000125
    CSI 5.28
    rCSI 20.12%
    PRS 98.57
  • regular ventricular cardiac myocyte CL0002131
    CSI 4.99
    rCSI 31.14%
    PRS 98.75
  • GABAergic neuron CL0000617
    CSI 4.63
    rCSI 15.51%
    PRS 97.15
  • serotonergic neuron CL0000850
    CSI 4.57
    rCSI 20.41%
    PRS 97.28
  • ON parasol ganglion cell CL4033052
    CSI 4.29
    rCSI 60.86%
    PRS 98.69
  • neural progenitor cell CL0011020
    CSI 3.65
    rCSI 16.07%
    PRS 96.88
  • renal principal cell CL0005009
    CSI 3.59
    rCSI 9.31%
    PRS 99.7
  • ON midget ganglion cell CL4033046
    CSI 2.96
    rCSI 60.33%
    PRS 98.55
  • OFF midget ganglion cell CL4033047
    CSI 2.94
    rCSI 59.94%
    PRS 98.6
  • direct pathway medium spiny neuron CL4023026
    CSI 2.48
    rCSI 59.49%
    PRS 97.68
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.46
    rCSI 59.3%
    PRS 97.65
  • H2 horizontal cell CL0004218
    CSI 2.42
    rCSI 12.05%
    PRS 99.02
  • vein endothelial cell of respiratory system CL4033008
    CSI 2.31
    rCSI 15.86%
    PRS 99.8
  • diffuse bipolar 2 cell CL4033028
    CSI 2.27
    rCSI 17.55%
    PRS 98.19
  • diffuse bipolar 3b cell CL4033030
    CSI 2.23
    rCSI 14.79%
    PRS 98.34

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 [ADAM23](/details-gene/8745) (ADAM metallopeptidase domain 23) is a protein-coding gene located on chromosome 2q33.3. It belongs to the ADAM (A Disintegrin And Metalloproteinase) family of proteins, which are type I transmembrane proteins known for their roles in cell-cell and cell-matrix interactions. Functionally, [ADAM23](/details-gene/8745) is implicated in '[cell adhesion](/details-cell/GO0007155)', particularly through '[integrin binding](/details-cell/GO0005178)', and possesses '[metallopeptidase activity](/details-cell/GO0008237)' ([Link](https://doi.org/10.1091/mbc.11.4.1457)). Expression data reveals that [ADAM23](/details-gene/8745) is a highly significant marker within the central nervous system, showing prominent expression across diverse neuronal subtypes, especially cortical interneurons and retinal neurons. This profile is consistent with its annotated roles in '[central nervous system development](/details-cell/GO0007417)' and its localization to the '[presynaptic membrane](/details-cell/GO0042734)'. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ADAM23](/details-gene/8745) demonstrates a strong and specific association with the nervous system. The gene exhibits its highest significance in various subtypes of GABAergic cortical interneurons, including '[pvalb GABAergic cortical interneuron](/details-cell/CL4023018)' (CSI: 39.39), '[VIP GABAergic cortical interneuron](/details-cell/CL4023016)' (CSI: 36.86), and '[lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)' (CSI: 33.10). This suggests a critical role for [ADAM23](/details-gene/8745) in the function or identity of these inhibitory neurons. In addition to interneurons, [ADAM23](/details-gene/8745) is also a significant marker for various glutamatergic neuron populations, such as the '[L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059)' (CSI: 24.84) and '[L4 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030063)' (CSI: 20.57). Its significance extends to the retina, where it is highly expressed in '[rod bipolar cell](/details-cell/CL0000751)' (CSI: 21.84) and '[retinal ganglion cell](/details-cell/CL0000740)' (CSI: 20.70). This broad yet specific neuronal expression pattern, first noted in early studies ([Link](https://doi.org/10.1042/bj3340093)), underscores its fundamental importance in neural circuit development and maintenance. ## Pathways and Molecular Function The molecular functions of [ADAM23](/details-gene/8745) are deeply intertwined with its cellular localization and biological roles. As a member of the ADAM family, it possesses both adhesion and proteolytic capabilities. Its function in '[cell adhesion](/details-cell/GO0007155)' is mediated in part by '[integrin binding](/details-cell/GO0005178)', a mechanism that allows it to facilitate interactions between cells and the extracellular matrix ([Link](https://doi.org/10.1091/mbc.11.4.1457)). This is critical for processes like neuronal migration and axon guidance during '[developmental biology](/details-cell/R-HSA-1266738)'. The gene product is an integral component of the '[plasma membrane](/details-cell/GO0005886)' and is specifically enriched in synaptic structures, including the '[glutamatergic synapse](/details-cell/GO0098978)' and the '[presynaptic membrane](/details-cell/GO0042734)'. Its involvement in '[Lgi-adam interactions](/details-cell/R-HSA-5682910)' is particularly noteworthy, as this pathway is crucial for synaptic transmission and has been linked to forms of epilepsy. While its '[metalloendopeptidase activity](/details-cell/GO0004222)' is a defining feature, the specific substrates of [ADAM23](/details-gene/8745) in the nervous system are not fully elucidated but are presumed to be involved in modulating the synaptic environment through '[proteolysis](/details-cell/GO0006508)'. Studies have also identified multiple isoforms of the gene that are differentially expressed during brain development ([Link](https://doi.org/10.1016/j.gene.2003.10.012)). ## Research Directions The specific and high-level expression of [ADAM23](/details-gene/8745) in distinct neuronal populations, coupled with its dual functions in adhesion and proteolysis, points to several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in multiple subtypes of cortical interneurons and its role in '[cell adhesion](/details-cell/GO0007155)', [ADAM23](/details-gene/8745) may be essential for the tangential migration and subsequent laminar integration of these neurons during corticogenesis. Its dysregulation could lead to defects in inhibitory circuit formation. 2. Based on its localization to the '[presynaptic membrane](/details-cell/GO0042734)' and its '[metalloendopeptidase activity](/details-cell/GO0004222)', [ADAM23](/details-gene/8745) likely functions as a key regulator of synaptic plasticity by cleaving specific cell surface or extracellular matrix proteins, thereby altering synaptic strength and structure. **Experimental Approach:** To test the hypothesis that [ADAM23](/details-gene/8745) modulates synaptic plasticity (Hypothesis 2), a conditional knockout (cKO) mouse model could be generated to specifically delete the gene in excitatory neurons of the hippocampus (e.g., using a CamKII-Cre driver). Electrophysiological recordings from hippocampal slices of these cKO mice could then be performed to assess for deficits in long-term potentiation (LTP) or long-term depression (LTD). Complementary proteomic analysis of synaptosome preparations from wild-type versus cKO mice could identify candidate protein substrates cleaved by [ADAM23](/details-gene/8745). **Therapeutic Potential:** As a cell-surface protein with enzymatic activity, [ADAM23](/details-gene/8745) presents a potentially druggable target. However, its widespread and critical role in the healthy adult brain suggests that systemic inhibition could lead to significant neurological side effects. Its therapeutic potential may be more relevant in pathologies where it is aberrantly expressed, such as in certain brain tumors (e.g., glioblastomas) where cell adhesion and proteolysis are dysregulated. In such a context, targeted delivery of a small molecule inhibitor or an antibody-drug conjugate designed to neutralize its function could represent a viable therapeutic strategy.

Genular Protein ID: 2967276130

Symbol: ADA23_HUMAN

Name: Disintegrin and metalloproteinase domain-containing protein 23

UniProtKB Accession Codes:

O75077 A2RU59

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 11 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 5 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 2 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9693107

Title: Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain.

PubMed ID: 9693107

DOI: 10.1042/bj3340093

PubMed ID: 10749942

Title: ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alpha v beta 3 integrin through an RGD-independent mechanism.

PubMed ID: 10749942

DOI: 10.1091/mbc.11.4.1457

PubMed ID: 14697522

Title: Two novel isoforms of Adam23 expressed in the developmental process of mouse and human brains.

PubMed ID: 14697522

DOI: 10.1016/j.gene.2003.10.012

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

Sequence Information:

  • Length: 832
  • Mass: 91926
  • Checksum: 7841A9670E1C24EF
  • Sequence:
    • MKPPGSSSRQ PPLAGCSLAG ASCGPQRGPA GSVPASAPAR TPPCRLLLVL LLLPPLAASS 
RPRAWGAAAP SAPHWNETAE KNLGVLADED NTLQQNSSSN ISYSNAMQKE ITLPSRLIYY 
INQDSESPYH VLDTKARHQQ KHNKAVHLAQ ASFQIEAFGS KFILDLILNN GLLSSDYVEI 
HYENGKPQYS KGGEHCYYHG SIRGVKDSKV ALSTCNGLHG MFEDDTFVYM IEPLELVHDE 
KSTGRPHIIQ KTLAGQYSKQ MKNLTMERGD QWPFLSELQW LKRRKRAVNP SRGIFEEMKY 
LELMIVNDHK TYKKHRSSHA HTNNFAKSVV NLVDSIYKEQ LNTRVVLVAV ETWTEKDQID 
ITTNPVQMLH EFSKYRQRIK QHADAVHLIS RVTFHYKRSS LSYFGGVCSR TRGVGVNEYG 
LPMAVAQVLS QSLAQNLGIQ WEPSSRKPKC DCTESWGGCI MEETGVSHSR KFSKCSILEY 
RDFLQRGGGA CLFNRPTKLF EPTECGNGYV EAGEECDCGF HVECYGLCCK KCSLSNGAHC 
SDGPCCNNTS CLFQPRGYEC RDAVNECDIT EYCTGDSGQC PPNLHKQDGY ACNQNQGRCY 
NGECKTRDNQ CQYIWGTKAA GSDKFCYEKL NTEGTEKGNC GKDGDRWIQC SKHDVFCGFL 
LCTNLTRAPR IGQLQGEIIP TSFYHQGRVI DCSGAHVVLD DDTDVGYVED GTPCGPSMMC 
LDRKCLQIQA LNMSSCPLDS KGKVCSGHGV CSNEATCICD FTWAGTDCSI RDPVRNLHPP 
KDEGPKGPSA TNLIIGSIAG AILVAAIVLG GTGWGFKNVK KRRFDPTQQG PI