Details for: MAMDC4

Gene ID: 158056

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: MAMDC4

Ensembl ID: ENSG00000177943

Description: MAM domain containing 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • intestinal epithelial cell CL0002563
    CSI 11.88
    rCSI 12.42%
    PRS 98.96
  • transit amplifying cell of colon CL0009011
    CSI 5.18
    rCSI 6.08%
    PRS 99.49
  • intestine goblet cell CL0019031
    CSI 4.5
    rCSI 3.99%
    PRS 98.92
  • glutamatergic neuron CL0000679
    CSI 3.69
    rCSI 7.59%
    PRS 95.61
  • colon epithelial cell CL0011108
    CSI 2.8
    rCSI 2.94%
    PRS 99.13
  • colonocyte CL1000347
    CSI 2.66
    rCSI 3.82%
    PRS 99.12
  • GABAergic neuron CL0000617
    CSI 2.45
    rCSI 8.21%
    PRS 95.45
  • colon goblet cell CL0009039
    CSI 1.68
    rCSI 3.98%
    PRS 99.26

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.

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  • 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)

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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 [MAMDC4](/details-gene/158056) (MAM domain containing 4) is a protein-coding gene located on chromosome 9q34.3 ([Link](https://pubmed.ncbi.nlm.nih.gov/15164053/)). It encodes a transmembrane glycoprotein characterized by a MAM (meprin, A5 protein, and receptor protein-tyrosine phosphatase mu) domain ([Link](https://pubmed.ncbi.nlm.nih.gov/12975309/)). Functionally, [MAMDC4](/details-gene/158056) is annotated as an apical endosomal glycoprotein involved in [protein transport](/details-cell/GO0015031). Expression data reveals its most significant role is within the gastrointestinal tract, where it serves as a prominent marker for [intestinal epithelial cells](/details-cell/CL0002563) and their progenitors, suggesting a key function in maintaining the structure and function of the gut lining. ## Cellular Roles and Expression Landscape The expression profile of [MAMDC4](/details-gene/158056) highlights its specialized role in specific cellular lineages, primarily within the intestinal epithelium. * **Dominant Role in Intestinal Epithelium:** **Overall** analysis shows that [MAMDC4](/details-gene/158056) is most significantly expressed in [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 11.88), including progenitor cells like the [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 5.18) and specialized secretory cells such as the [intestine goblet cell](/details-cell/CL0019031) (CSI: 4.50). Its high significance in both mature and developing cell types of the colon suggests a continuous role in the establishment and maintenance of the intestinal mucosal barrier. * **Secondary Expression in Neuronal Subtypes:** A secondary, yet notable, expression signal is observed in specific neuronal populations, including the [glutamatergic neuron](/details-cell/CL0000679) (CSI: 3.69) and [GABAergic neuron](/details-cell/CL0000617) (CSI: 2.45). This suggests that [MAMDC4](/details-gene/158056) may have a distinct, albeit less prominent, function related to protein trafficking within the central nervous system. The data strongly indicates that the primary biological footprint of this gene is within the digestive system. ## Pathways and Molecular Function The known molecular functions of [MAMDC4](/details-gene/158056) are highly consistent with its observed cellular expression pattern. * **Protein Trafficking in Polarized Cells:** The gene's involvement in [protein transport](/details-cell/GO0015031) and its localization to the [Golgi apparatus](/details-cell/GO0005794) and cell [membrane](/details-cell/GO0016020) are central to its function. As an apical endosomal glycoprotein, it likely participates in the complex sorting and trafficking machinery required by polarized cells. In [intestinal epithelial cells](/details-cell/CL0002563), which possess distinct apical (lumen-facing) and basolateral surfaces, such machinery is critical for directing proteins to their correct locations to mediate absorption, secretion, and barrier maintenance. The function of [MAMDC4](/details-gene/158056) is likely tied to the transport of specific cargo proteins to the apical membrane. ## Research Directions The specific role of [MAMDC4](/details-gene/158056) in intestinal health and disease remains an important area for future investigation. **Proposed Hypotheses:** 1. Given its high expression in [intestinal epithelial cells](/details-cell/CL0002563) and its role in protein transport, [MAMDC4](/details-gene/158056) is essential for maintaining intestinal barrier integrity by regulating the trafficking of key apical membrane proteins, such as digestive enzymes, nutrient transporters, or junctional complex components. 2. The expression of [MAMDC4](/details-gene/158056) in progenitor cells, specifically [transit amplifying cells of the colon](/details-cell/CL0009011), suggests it plays a role during epithelial differentiation, possibly by mediating the correct localization of cell fate determinants or proteins required for specialized cell functions like mucus production in [goblet cells](/details-cell/CL0019031). 3. In the nervous system, the presence of [MAMDC4](/details-gene/158056) in [glutamatergic](/details-cell/CL0000679) and [GABAergic neurons](/details-cell/CL0000617) points to a potential role in synaptic function, perhaps by participating in the endosomal sorting and recycling of neurotransmitter receptors or ion channels. **Key Experimental Approach:** To test the hypothesis that [MAMDC4](/details-gene/158056) is critical for intestinal barrier function, a conditional knockout mouse model could be generated using a Villin-Cre driver to specifically delete the gene in intestinal epithelial cells. These mice could then be challenged with dextran sulfate sodium (DSS) to induce colitis, with barrier permeability assessed using an *in vivo* FITC-dextran assay. Organoids derived from the knockout mice would allow for detailed molecular analysis, including immunofluorescence to examine the localization of apical junction proteins (e.g., ZO-1, claudins) and mass spectrometry-based proteomics of the apical membrane to identify the specific protein cargo whose transport is dependent on [MAMDC4](/details-gene/158056). **Therapeutic Potential:** As a membrane protein with highly specific expression in the intestinal epithelium, [MAMDC4](/details-gene/158056) presents a potential target for therapies aimed specifically at the gut. If its dysregulation is linked to impaired barrier function in pathologies like Inflammatory Bowel Disease (IBD) or celiac disease, strategies to modulate its expression or function could offer a novel therapeutic avenue. For example, it could be a target for antibody-based therapies designed to either restore proper protein trafficking or deliver a payload exclusively to intestinal epithelial cells. Further research is required to validate its role in disease before its druggability can be fully determined.

Genular Protein ID: 325506118

Symbol: AEGP_HUMAN

Name: Apical endosomal glycoprotein

UniProtKB Accession Codes:

Q6UXC1 A2A3D4 B0QZ81 Q5T5S2 Q8NCX7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 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 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 1216
  • Mass: 131499
  • Checksum: 6E2957EDE7AD2465
  • Sequence:
    • MPLSSHLLPA LVLFLAGSSG WAWVPNHCRS PGQAVCNFVC DCRDCSDEAQ CGYHGASPTL 
GAPFACDFEQ DPCGWRDIST SGYSWLRDRA GAALEGPGPH SDHTLGTDLG WYMAVGTHRG 
KEASTAALRS PTLREAASSC KLRLWYHAAS GDVAELRVEL THGAETLTLW QSTGPWGPGW 
QELAVTTGRI RGDFRVTFSA TRNATHRGAV ALDDLEFWDC GLPTPQANCP PGHHHCQNKV 
CVEPQQLCDG EDNCGDLSDE NPLTCGRHIA TDFETGLGPW NRSEGWSRNH RAGGPERPSW 
PRRDHSRNSA QGSFLVSVAE PGTPAILSSP EFQASGTSNC SLVFYQYLSG SEAGCLQLFL 
QTLGPGAPRA PVLLRRRRGE LGTAWVRDRV DIQSAYPFQI LLAGQTGPGG VVGLDDLILS 
DHCRPVSEVS TLQPLPPGPR APAPQPLPPS SRLQDSCKQG HLACGDLCVP PEQLCDFEEQ 
CAGGEDEQAC GTTDFESPEA GGWEDASVGR LQWRRVSAQE SQGSSAAAAG HFLSLQRAWG 
QLGAEARVLT PLLGPSGPSC ELHLAYYLQS QPRGFLALVV VDNGSRELAW QALSSSAGIW 
KVDKVLLGAR RRPFRLEFVG LVDLDGPDQQ GAGVDNVTLR DCSPTVTTER DREVSCNFER 
DTCSWYPGHL SDTHWRWVES RGPDHDHTTG QGHFVLLDPT DPLAWGHSAH LLSRPQVPAA 
PTECLSFWYH LHGPQIGTLR LAMRREGEET HLWSRSGTQG NRWHEAWATL SHQPGSHAQY 
QLLFEGLRDG YHGTMALDDV AVRPGPCWAP NYCSFEDSDC GFSPGGQGLW RRQANASGHA 
AWGPPTDHTT ETAQGHYMVV DTSPDALPRG QTASLTSKEH RPLAQPACLT FWYHGSLRSP 
GTLRVYLEER GRHQVLSLSA HGGLAWRLGS MDVQAERAWR VVFEAVAAGV AHSYVALDDL 
LLQDGPCPQP GSCDFESGLC GWSHLAWPGL GGYSWDWGGG ATPSRYPQPP VDHTLGTEAG 
HFAFFETGVL GPGGRAAWLR SEPLPATPAS CLRFWYHMGF PEHFYKGELK VLLHSAQGQL 
AVWGAGGHRR HQWLEAQVEV ASAKEFQIVF EATLGGQPAL GPIALDDVEY LAGQHCQQPA 
PSPGNTAAPG SVPAVVGSAL LLLMLLVLLG LGGRRWLQKK GSCPFQSNTE ATAPGFDNIL 
FNADGVTLPA SVTSDP