Details for: HEPACAM2

Gene ID: 253012

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: HEPACAM2

Ensembl ID: ENSG00000188175

Description: HEPACAM family member 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • M cell of gut CL0000682
    CSI 38.52
    rCSI 40.93%
    PRS 79.68
  • intestine goblet cell CL0019031
    CSI 36.58
    rCSI 32.47%
    PRS 70.6
  • pulmonary ionocyte CL0017000
    CSI 36.28
    rCSI 44.16%
    PRS 79.73
  • small intestine goblet cell CL1000495
    CSI 32.77
    rCSI 71.76%
    PRS 79.26
  • goblet cell CL0000160
    CSI 29.9
    rCSI 28.26%
    PRS 71.98
  • colon goblet cell CL0009039
    CSI 28.19
    rCSI 67%
    PRS 79.89
  • renal alpha-intercalated cell CL0005011
    CSI 28.1
    rCSI 37.56%
    PRS 80.49
  • intestinal tuft cell CL0019032
    CSI 27.98
    rCSI 42.77%
    PRS 77.03
  • lung neuroendocrine cell CL1000223
    CSI 26.21
    rCSI 38.77%
    PRS 77.49
  • ionocyte CL0005006
    CSI 25.24
    rCSI 27.06%
    PRS 73.34
  • tuft cell of colon CL0009041
    CSI 24.79
    rCSI 57.76%
    PRS 81.04
  • BEST4+ enteroycte CL4030026
    CSI 23.88
    rCSI 29.71%
    PRS 74.19
  • enteroendocrine cell of small intestine CL0009006
    CSI 22.57
    rCSI 49.7%
    PRS 82.91
  • pancreatic D cell CL0000173
    CSI 20.86
    rCSI 20.52%
    PRS 75.48
  • pancreatic epsilon cell CL0005019
    CSI 18.99
    rCSI 88.54%
    PRS 84.7
  • transit amplifying cell of colon CL0009011
    CSI 17.89
    rCSI 21.01%
    PRS 74.75
  • enteroendocrine cell CL0000164
    CSI 17.83
    rCSI 24.36%
    PRS 73.48
  • regulatory T cell CL0000815
    CSI 17.43
    rCSI 20.21%
    PRS 77.61
  • P/D1 enteroendocrine cell CL0002268
    CSI 15.72
    rCSI 85.58%
    PRS 83.48
  • renal beta-intercalated cell CL0002201
    CSI 15.6
    rCSI 37.18%
    PRS 73.01
  • neuroendocrine cell CL0000165
    CSI 13.98
    rCSI 54.07%
    PRS 83.97
  • brush cell CL0002204
    CSI 11.9
    rCSI 23.56%
    PRS 84.49
  • erythrocyte CL0000232
    CSI 11.46
    rCSI 26.01%
    PRS 74.56
  • type EC enteroendocrine cell CL0000577
    CSI 10.7
    rCSI 37.97%
    PRS 78.81
  • type L enteroendocrine cell CL0002279
    CSI 7.99
    rCSI 14.99%
    PRS 83.16
  • paneth cell of epithelium of small intestine CL1000343
    CSI 7.45
    rCSI 20.89%
    PRS 81.86
  • enteroendocrine cell of colon CL0009042
    CSI 6.43
    rCSI 30.16%
    PRS 84.87
  • pancreatic PP cell CL0002275
    CSI 6.37
    rCSI 25.37%
    PRS 82.36
  • basal cell of epidermis CL0002187
    CSI 6.28
    rCSI 11.14%
    PRS 43.35
  • pancreatic A cell CL0000171
    CSI 4.68
    rCSI 4.91%
    PRS 76.15
  • melanocyte of skin CL1000458
    CSI 4.63
    rCSI 6.31%
    PRS 40.41
  • paneth cell of colon CL0009009
    CSI 4.55
    rCSI 44.66%
    PRS 84.89
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 4.31
    rCSI 5.22%
    PRS 55.47
  • paneth cell CL0000510
    CSI 3.8
    rCSI 5.62%
    PRS 85.23
  • suprabasal keratinocyte CL4033013
    CSI 3.31
    rCSI 5.41%
    PRS 40.04
  • endocrine cell CL0000163
    CSI 3.26
    rCSI 16.75%
    PRS 91.75
  • helper T cell CL0000912
    CSI 3.01
    rCSI 4.26%
    PRS 74.22
  • innate lymphoid cell CL0001065
    CSI 1.19
    rCSI 2.45%
    PRS 71.48
  • type B pancreatic cell CL0000169
    CSI 0.63
    rCSI 1.4%
    PRS 71.67

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)

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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 [HEPACAM2](/details-gene/253012) (HEPACAM family member 2) is a protein-coding gene located on chromosome 7q21.2. Functional annotations strongly implicate [HEPACAM2](/details-gene/253012) in the fundamental process of cell division, with specific roles in the [centrosome cycle](/details-ontology/GO:0007098) and the structural integrity of the [mitotic spindle](/details-ontology/GO:0072686) and [midbody](/details-ontology/GO:0030496). **Overall**, expression data reveals a highly specific enrichment in specialized epithelial cell populations, particularly secretory and sensory cells of the gastrointestinal tract and respiratory system. This includes high significance in [M cell of gut](/details-cell/CL0000682), [intestine goblet cell](/details-cell/CL0019031), and [pulmonary ionocyte](/details-cell/CL0017000), suggesting it serves as a key marker and functional component of these distinct cellular lineages. ## Cellular Roles and Expression Landscape The expression profile of [HEPACAM2](/details-gene/253012) indicates a specialized function rather than ubiquitous housekeeping activity. **Overall**, the gene demonstrates its highest significance in a variety of rare and functionally distinct epithelial cell types. Its most prominent expression is observed in cells of the gastrointestinal mucosa, including [M cell of gut](/details-cell/CL0000682) (CSI: 38.52), various types of [goblet cell](/details-cell/CL0000160)s such as [intestine goblet cell](/details-cell/CL0019031) (CSI: 36.58) and [colon goblet cell](/details-cell/CL0009039) (CSI: 28.19), as well as sensory [intestinal tuft cell](/details-cell/CL0019032) (CSI: 27.98). Beyond the gut, [HEPACAM2](/details-gene/253012) is a defining marker for [pulmonary ionocyte](/details-cell/CL0017000) (CSI: 36.28), a specialized cell in the airway epithelium. The gene's significance extends to other specialized epithelial contexts, including the [renal alpha-intercalated cell](/details-cell/CL0005011) (CSI: 28.10) involved in acid-base homeostasis, and certain endocrine cells like the [pancreatic D cell](/details-cell/CL0000173) (CSI: 20.86). This pattern suggests that [HEPACAM2](/details-gene/253012) is a key component in the biology of terminally differentiated secretory and ion-transporting epithelial cells. ## Pathways and Molecular Function The functional annotations for [HEPACAM2](/details-gene/253012) provide a clear mechanistic basis for a role in cell proliferation. It is significantly associated with the biological processes of [cell division](/details-ontology/GO:0051301) and the [centrosome cycle](/details-ontology/GO:0007098). This is strongly supported by its localization to critical structures involved in mitosis, including the [centrosome](/details-ontology/GO:0005813), [mitotic spindle](/details-ontology/GO:0072686), [spindle](/details-ontology/GO:0005819), and the [midbody](/details-ontology/GO:0030496), which is essential for the final stage of cytokinesis. Research has confirmed this function, demonstrating that poly-ADP ribosylation of [HEPACAM2](/details-gene/253012) (under its alias Miki) by tankyrase-1 is a key step in promoting centrosome maturation ([Link](https://doi.org/10.1016/j.molcel.2012.06.033)). The gene's molecular function is annotated as [protein binding](/details-ontology/GO:0005515), which is consistent with its role as a structural component of these large protein-based cellular machines. Additionally, its localization to the [Golgi apparatus](/details-ontology/GO:0005794) and [Golgi membrane](/details-ontology/GO:0000139) may suggest a role in protein processing or trafficking, which could be relevant to the highly secretory nature of the cell types where it is most prominently expressed, such as [goblet cell](/details-cell/CL0000160)s. ## Research Directions The dual profile of [HEPACAM2](/details-gene/253012)—a core component of the cell division machinery with highly specific expression in differentiated epithelial tissues—presents intriguing questions about its biological roles in health and disease. Its association with myeloid leukemia and myelodysplastic syndrome via microdeletions ([Link](https://doi.org/10.1016/j.bbrc.2009.04.004)) and its identification in the consensus coding sequences of breast and colorectal cancers ([Link](https://doi.org/10.1126/science.1133427)) highlight its potential clinical relevance. **Proposed Hypotheses:** 1. Given its high expression in the rapidly renewing intestinal epithelium and its fundamental role in the centrosome cycle, dysregulation of [HEPACAM2](/details-gene/253012) may compromise mitotic fidelity, leading to aneuploidy and contributing to the initiation or progression of colorectal cancer. 2. In terminally differentiated, non-proliferating cells like [pulmonary ionocyte](/details-cell/CL0017000)s and [renal alpha-intercalated cell](/details-cell/CL0005011)s, [HEPACAM2](/details-gene/253012) may be repurposed from its cell cycle role to a structural one, potentially organizing the microtubule network required for the precise trafficking and localization of ion channels and transporters to the plasma membrane. **Experimental Approach:** To test the first hypothesis regarding its role in colorectal cancer, a conditional knockout of [HEPACAM2](/details-gene/253012) could be generated in the murine intestinal epithelium (e.g., *Villin-CreERT2; Hepacam2 fl/fl*). Following gene deletion, intestinal organoids could be cultured to assess the impact on crypt proliferation, cell fate specification, and genomic stability. These mice could then be challenged with a colitis-associated cancer model (e.g., AOM/DSS) to determine if loss of [HEPACAM2](/details-gene/253012) alters tumor incidence, growth, or cellular composition, which could be analyzed by single-cell RNA sequencing. **Therapeutic Potential:** As a protein integral to the cell cycle, [HEPACAM2](/details-gene/253012) represents a potential therapeutic target in hyperproliferative diseases like cancer. Its role in centrosome maturation suggests that its **inhibition** could induce mitotic arrest or cell death in rapidly dividing cancer cells. If, as some evidence suggests, it is a transmembrane protein ([Link](https://doi.org/10.1101/gr.1293003)), its restricted expression pattern outside of cancer could make it an attractive target for antibody-based therapies in malignancies where it is aberrantly expressed. However, if it functions exclusively intracellularly, development of small molecule inhibitors that disrupt its protein-protein interactions would be the more viable strategy.

Genular Protein ID: 3618533522

Symbol: HECA2_HUMAN

Name: HEPACAM family member 2

UniProtKB Accession Codes:

A8MVW5 B3KTT4 B4DPJ1 B9EG93 E9PDV5 Q6UXI0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 10 Gene3D 1 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 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 4 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

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: 19358830

Title: Identification of a common microdeletion cluster in 7q21.3 subband among patients with myeloid leukemia and myelodysplastic syndrome.

PubMed ID: 19358830

DOI: 10.1016/j.bbrc.2009.04.004

PubMed ID: 22864114

Title: Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation.

PubMed ID: 22864114

DOI: 10.1016/j.molcel.2012.06.033

PubMed ID: 16959974

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

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 21248752

Title: Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.

PubMed ID: 21248752

DOI: 10.1038/nature09639

Sequence Information:

  • Length: 462
  • Mass: 51407
  • Checksum: E38DE6E4CCAA6BC2
  • Sequence:
    • MGQDAFMEPF GDTLGVFQCK IYLLLFGACS GLKVTVPSHT VHGVRGQALY LPVHYGFHTP 
ASDIQIIWLF ERPHTMPKYL LGSVNKSVVP DLEYQHKFTM MPPNASLLIN PLQFPDEGNY 
IVKVNIQGNG TLSASQKIQV TVDDPVTKPV VQIHPPSGAV EYVGNMTLTC HVEGGTRLAY 
QWLKNGRPVH TSSTYSFSPQ NNTLHIAPVT KEDIGNYSCL VRNPVSEMES DIIMPIIYYG 
PYGLQVNSDK GLKVGEVFTV DLGEAILFDC SADSHPPNTY SWIRRTDNTT YIIKHGPRLE 
VASEKVAQKT MDYVCCAYNN ITGRQDETHF TVIITSVGLE KLAQKGKSLS PLASITGISL 
FLIISMCLLF LWKKYQPYKV IKQKLEGRPE TEYRKAQTFS GHEDALDDFG IYEFVAFPDV 
SGVSRIPSRS VPASDCVSGQ DLHSTVYEVI QHIPAQQQDH PE

Genular Protein ID: 2409186195

Symbol: C9JN07_HUMAN

Name: N/A

UniProtKB Accession Codes:

C9JN07

Database IDs:

ARBA 5 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 4 Gene3D 1 GeneTree 1 HGNC 1 InterPro 6 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 3 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 2 SMART 2 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 455
  • Mass: 51061
  • Checksum: 6B9B383D723971F0
  • Sequence:
    • MWLKVFTTFL SFATGACSGL KVTVPSHTVH GVRGQALYLP VHYGFHTPAS DIQIIWLFER 
PHTMPKYLLG SVNKSVVPDL EYQHKFTMMP PNASLLINPL QFPDEGNYIV KVNIQGNGTL 
SASQKIQVTV DDPVTKPVVQ IHPPSGAVEY VGNMTLTCHV EGGTRLAYQW LKNGRPVHTS 
STYSFSPQNN TLHIAPVTKE DIGNYSCLVR NPVSEMESDI IMPIIYYGPY GLQVNSDKGL 
KVGEVFTVDL GEAILFDCSA DSHPPNTYSW IRRTDNTTYI IKHGPRLEVA SEKVAQKTMD 
YVCCAYNNIT GRQDETHFTV IITSVGLEKL AQKGKSLSPL ASITGISLFL IISMCLLFLW 
KKYQPYKGQK QNTGKLKHFQ AMKMLWMTSE YMNLLLFQMF LVFPGSQAGL FQPLIVYRGK 
ICTVQCMKLF STSLPSSKTI QSELSWAKQY IRVKF