Details for: REG1A

Gene ID: 5967

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: REG1A

Ensembl ID: ENSG00000115386

Description: regenerating family member 1 alpha

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • pancreatic acinar cell CL0002064
    CSI 59.06
    rCSI 78.5%
    PRS 15.53
  • paneth cell CL0000510
    CSI 51.68
    rCSI 76.3%
    PRS 22.3
  • stem cell CL0000034
    CSI 45.56
    rCSI 43.93%
    PRS 9.96
  • transit amplifying cell CL0009010
    CSI 34.51
    rCSI 52.78%
    PRS 23.07
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 30.17
    rCSI 81.32%
    PRS 18.27
  • goblet cell CL0000160
    CSI 30
    rCSI 28.35%
    PRS 14.82
  • paneth cell of epithelium of small intestine CL1000343
    CSI 26.57
    rCSI 74.47%
    PRS 21.93
  • mucous neck cell CL0000651
    CSI 25.15
    rCSI 36.25%
    PRS 22.72
  • colon epithelial cell CL0011108
    CSI 23.91
    rCSI 25.05%
    PRS 13.23
  • pancreatic ductal cell CL0002079
    CSI 23.9
    rCSI 46.48%
    PRS 14.53
  • transit amplifying cell of small intestine CL0009012
    CSI 18.73
    rCSI 82.24%
    PRS 26.35
  • intestine goblet cell CL0019031
    CSI 15.08
    rCSI 13.38%
    PRS 14.21
  • plasma cell CL0000786
    CSI 14.88
    rCSI 19.5%
    PRS 56.83
  • colonocyte CL1000347
    CSI 12.52
    rCSI 17.95%
    PRS 19.48
  • M cell of gut CL0000682
    CSI 11.45
    rCSI 12.17%
    PRS 25.04
  • enterocyte CL0000584
    CSI 11.11
    rCSI 17.92%
    PRS 22.55
  • epithelial cell of proximal tubule CL0002306
    CSI 11.08
    rCSI 27.05%
    PRS 14.1
  • pancreatic D cell CL0000173
    CSI 8.71
    rCSI 8.57%
    PRS 15.47
  • enteroendocrine cell CL0000164
    CSI 8.47
    rCSI 11.57%
    PRS 15.74
  • small intestine goblet cell CL1000495
    CSI 8.12
    rCSI 17.79%
    PRS 18.93
  • pancreatic A cell CL0000171
    CSI 7.52
    rCSI 7.88%
    PRS 15.19
  • brush cell CL0002204
    CSI 7.02
    rCSI 13.9%
    PRS 35.97
  • myofibroblast cell CL0000186
    CSI 6.37
    rCSI 8.83%
    PRS 20.37
  • type EC enteroendocrine cell CL0000577
    CSI 6.18
    rCSI 21.92%
    PRS 23.2
  • BEST4+ enteroycte CL4030026
    CSI 6.16
    rCSI 7.66%
    PRS 15
  • peptic cell CL0000155
    CSI 5.97
    rCSI 58.77%
    PRS 40.37
  • enterocyte of epithelium of small intestine CL1000334
    CSI 5.61
    rCSI 86.75%
    PRS 34.89
  • transit amplifying cell of colon CL0009011
    CSI 5.39
    rCSI 6.33%
    PRS 16.7
  • intestinal tuft cell CL0019032
    CSI 5.37
    rCSI 8.21%
    PRS 16.27
  • IgA plasma cell CL0000987
    CSI 5.28
    rCSI 5.41%
    PRS 26.43
  • colon goblet cell CL0009039
    CSI 5.14
    rCSI 12.22%
    PRS 21.33
  • glial cell CL0000125
    CSI 4.64
    rCSI 17.68%
    PRS 14.27
  • enteroendocrine cell of colon CL0009042
    CSI 4.56
    rCSI 21.39%
    PRS 37.25
  • plasmacytoid dendritic cell CL0000784
    CSI 4.31
    rCSI 4.36%
    PRS 64.33
  • pancreatic stellate cell CL0002410
    CSI 3.08
    rCSI 17.92%
    PRS 21.38
  • type B pancreatic cell CL0000169
    CSI 2.68
    rCSI 5.94%
    PRS 13.24
  • foveolar cell of stomach CL0002179
    CSI 2.27
    rCSI 4.82%
    PRS 22.83
  • pancreatic PP cell CL0002275
    CSI 2.04
    rCSI 8.14%
    PRS 24.92
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.03
    rCSI 4.47%
    PRS 21.7
  • pancreatic epsilon cell CL0005019
    CSI 0.57
    rCSI 2.65%
    PRS 33.18
  • intraepithelial lymphocyte CL0002496
    CSI -0.11
    rCSI -0.29%
    PRS 53.7
  • IgG plasma cell CL0000985
    CSI -9.19
    rCSI -11.01%
    PRS 24.51

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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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 [REG1A](/details-gene/5967), or Regenerating Family Member 1 Alpha, is a protein-coding gene located on chromosome 2p12. It encodes a secreted protein, also known as lithostathine-1-alpha or pancreatic stone protein, which was initially identified for its role in pancreatic regeneration and its ability to inhibit the formation of calcium carbonate stones in the pancreas [Link](https://doi.org/10.1172/jci114128), [Link](https://doi.org/10.1016/s0021-9258(18)69176-8). **Overall**, expression data reveals that [REG1A](/details-gene/5967) is a highly significant marker for secretory and progenitor cell populations within the gastrointestinal system. Its functions are linked to cell proliferation, innate immunity, and tissue homeostasis, particularly in the exocrine pancreas and intestinal epithelium. Its clinical relevance is associated with conditions like pancreatitis, and it is documented in OMIM under entry [167770](https://omim.org/entry/167770). ## Cellular Roles and Expression Landscape The expression profile of [REG1A](/details-gene/5967) strongly indicates a specialized role in the glandular and regenerative tissues of the digestive system. **Overall**, the gene exhibits its highest significance in secretory cells of the exocrine pancreas and intestine. It is a top marker for `[pancreatic acinar cell](/details-cell/CL0002064)` (CSI: 59.06) and `[pancreatic ductal cell](/details-cell/CL0002079)` (CSI: 23.90), consistent with its original characterization as a major secretory product of the pancreas. Its high significance in `[paneth cell](/details-cell/CL0000510)` (CSI: 51.68) and `[goblet cell](/details-cell/CL0000160)` (CSI: 30.00) highlights its role in the innate defense and mucosal barrier of the intestine. Furthermore, [REG1A](/details-gene/5967) is prominently associated with regenerative cell compartments. Its high CSI scores in `[stem cell](/details-cell/CL0000034)` (CSI: 45.56), `[transit amplifying cell](/details-cell/CL0009010)` (CSI: 34.51), and `[intestinal crypt stem cell of small intestine](/details-cell/CL0009017)` (CSI: 30.17) underscore its likely involvement in tissue renewal and repair. Conversely, the gene shows very low to negative significance in mature lymphocyte populations, such as `[IgG plasma cell](/details-cell/CL0000985)` (CSI: -9.19) and `[intraepithelial lymphocyte](/details-cell/CL0002496)` (CSI: -0.11). This pattern suggests that while [REG1A](/details-gene/5967) contributes to antimicrobial humoral immunity, its function is primarily executed by epithelial cells rather than by cells of the adaptive immune system. ## Pathways and Molecular Function Functional annotation aligns closely with the observed cellular expression pattern, pointing to a dual role in tissue growth and host defense. [REG1A](/details-gene/5967) is an extracellular protein found in the `extracellular space` ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) and `extracellular exosome` ([GO:0070062](https://www.ebi.ac.uk/QuickGO/term/GO:0070062)). Its proliferative and regenerative functions are supported by its annotation for `growth factor activity` ([GO:0008083](https://www.ebi.ac.uk/QuickGO/term/GO:0008083)) and its involvement in the `positive regulation of cell population proliferation` ([GO:0008284](https://www.ebi.ac.uk/QuickGO/term/GO:0008284)). This is highly consistent with its strong expression in intestinal and pancreatic stem and transit amplifying cells, where it likely acts as a mitogenic factor to promote tissue maintenance and repair. The gene's role in innate immunity is defined by its participation in the `antimicrobial humoral immune response mediated by antimicrobial peptide` ([GO:0061844](https://www.ebi.ac.uk/QuickGO/term/GO:0061844)). This is further specified by its molecular ability to bind to bacterial cell wall components, as indicated by `peptidoglycan binding` ([GO:0042834](https://www.ebi.ac.uk/QuickGO/term/GO:0042834)). This function is consistent with its high expression in `[paneth cell](/details-cell/CL0000510)`, which are key producers of antimicrobial proteins in the gut. ## Research Directions The specific expression pattern and dual functionality of [REG1A](/details-gene/5967) in both regeneration and host defense suggest several avenues for future investigation. Its concentration in tissues that form a critical barrier with the external environment makes it a key player in gastrointestinal health and disease. **Proposed Hypotheses:** 1. Given its potent growth factor activity and high expression in the intestinal crypt, [REG1A](/details-gene/5967) acts as a critical niche signal that is necessary for the maintenance and proliferation of `[intestinal crypt stem cell of small intestine](/details-cell/CL0009017)`, particularly during recovery from epithelial injury. 2. The peptidoglycan-binding capacity of [REG1A](/details-gene/5967) suggests that it selectively modulates the gut microbiome. We hypothesize that [REG1A](/details-gene/5967) directly inhibits the growth of specific Gram-positive bacteria, thereby helping to maintain a healthy microbial balance at the mucosal surface. **Experimental Approach:** To test the role of [REG1A](/details-gene/5967) in intestinal epithelial regeneration (Hypothesis 1), one could utilize an *in vitro* organoid model. Intestinal crypts could be isolated from `REG1A` knockout mice and wild-type controls to generate organoids. The growth, budding efficiency, and cell proliferation rates (via EdU incorporation) of these organoids would be compared under baseline conditions and following injury induced by irradiation. A key experiment would be to add recombinant REG1A protein to the knockout organoid cultures to determine if it can rescue the regenerative phenotype, thus confirming its direct role as an extrinsic growth factor. **Therapeutic Potential:** As a secreted protein with pro-regenerative properties highly specific to the gastrointestinal tract, [REG1A](/details-gene/5967) presents significant therapeutic potential. It is a candidate for **activation or protein-replacement therapy** rather than inhibition. Administration of recombinant REG1A could be explored as a treatment for conditions characterized by mucosal damage, such as inflammatory bowel disease (IBD), chemotherapy-induced mucositis, or short bowel syndrome, to accelerate epithelial repair and restore barrier function.

Genular Protein ID: 2544823070

Symbol: REG1A_HUMAN

Name: Lithostathine-1-alpha

UniProtKB Accession Codes:

P05451 P11379 Q4ZG28

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 EMBL 9 Ensembl 1 EvolutionaryTrace 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 UCSC 1 UniLectin 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2963000

Title: A novel gene activated in regenerating islets.

PubMed ID: 2963000

DOI: 10.1016/s0021-9258(18)69176-8

PubMed ID: 2332435

Title: Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. The reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene.

PubMed ID: 2332435

DOI: 10.1016/s0021-9258(19)39132-x

PubMed ID: 2525567

Title: Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis.

PubMed ID: 2525567

DOI: 10.1172/jci114128

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 3665916

Title: Complete amino acid sequence of an immunoreactive form of human pancreatic stone protein isolated from pancreatic juice.

PubMed ID: 3665916

DOI: 10.1111/j.1432-1033.1987.tb13405.x

PubMed ID: 3541906

Title: Partial amino acid sequence of human pancreatic stone protein, a novel pancreatic secretory protein.

PubMed ID: 3541906

DOI: 10.1042/bj2380227

PubMed ID: 3908481

Title: Isolation, characterization, and distribution of an unusual pancreatic human secretory protein.

PubMed ID: 3908481

DOI: 10.1172/jci112216

PubMed ID: 2493268

Title: N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue.

PubMed ID: 2493268

DOI: 10.1016/0167-4838(89)90305-1

PubMed ID: 3108036

Title: Cleavage of the Arg-Ile bond in the native polypeptide chain of human pancreatic stone protein.

PubMed ID: 3108036

DOI: 10.1016/0014-5793(87)80688-9

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 2764894

Title: The human reg gene encodes pancreatic stone protein.

PubMed ID: 2764894

DOI: 10.1042/bj2600622

PubMed ID: 2226837

Title: Isolation and characterization of human reg protein produced in Saccharomyces cerevisiae.

PubMed ID: 2226837

DOI: 10.1016/0014-5793(90)80454-q

PubMed ID: 2394826

Title: Enhanced expression of an exocrine pancreatic protein in Alzheimer's disease and the developing human brain.

PubMed ID: 2394826

DOI: 10.1172/jci114762

PubMed ID: 8654365

Title: Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation.

PubMed ID: 8654365

DOI: 10.1002/j.1460-2075.1996.tb00628.x

PubMed ID: 10625646

Title: Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine.

PubMed ID: 10625646

DOI: 10.1074/jbc.275.2.1057

PubMed ID: 8961348

Title: What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy.

PubMed ID: 8961348

DOI: 10.1093/protein/9.11.949

Sequence Information:

  • Length: 166
  • Mass: 18731
  • Checksum: EF93C760DC2DBCC3
  • Sequence:
    • MAQTSSYFML ISCLMFLSQS QGQEAQTELP QARISCPEGT NAYRSYCYYF NEDRETWVDA 
DLYCQNMNSG NLVSVLTQAE GAFVASLIKE SGTDDFNVWI GLHDPKKNRR WHWSSGSLVS 
YKSWGIGAPS SVNPGYCVSL TSSTGFQKWK DVPCEDKFSF VCKFKN

Genular Protein ID: 2004599297

Symbol: A8K7G6_HUMAN

Name: N/A

UniProtKB Accession Codes:

A8K7G6

Database IDs:

ARBA 2 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 9 Gene3D 1 InterPro 5 KEGG 1 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 3 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 1 SAM 1 SMART 1 SUPFAM 1

Sequence Information:

  • Length: 166
  • Mass: 18732
  • Checksum: E173C760DC2DBCC3
  • Sequence:
    • MAQTSSYFML ISCLMFLSQS QGQEAQTELP QARISCPEGT NAYRSYCYYF NEDRETWVDA 
DLYCQNMNSG NLVSVLTQAE GAFVASLIKE SGTDDFNVWI GLHDPKKNRR WHWSSGSLVS 
YKSWGIGAPS SVNPGYCVSL TSSTGFQKWK DVPCEDKFSF VCKFKD