Details for: REEP6

Gene ID: 92840

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: REEP6

Ensembl ID: ENSG00000115255

Description: receptor accessory protein 6

Cell Significance Landscape

Associated with

Significant Cells

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

  • intestinal epithelial cell CL0002563
    CSI 14.35
    rCSI 15%
    PRS 97.38
  • colonocyte CL1000347
    CSI 11.04
    rCSI 15.82%
    PRS 97.65
  • enterocyte CL0000584
    CSI 6.06
    rCSI 9.78%
    PRS 96.76
  • midzonal region hepatocyte CL0019028
    CSI 5.59
    rCSI 13.12%
    PRS 96.34
  • goblet cell CL0000160
    CSI 5.06
    rCSI 4.78%
    PRS 97.6
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4.76
    rCSI 3.69%
    PRS 99.11
  • colon epithelial cell CL0011108
    CSI 4.22
    rCSI 4.42%
    PRS 97.71
  • retinal rod cell CL0000604
    CSI 3.89
    rCSI 6.86%
    PRS 96.36
  • enteroendocrine cell CL0000164
    CSI 3.88
    rCSI 5.3%
    PRS 97.16
  • Kupffer cell CL0000091
    CSI 3.61
    rCSI 8.25%
    PRS 98.49
  • intestine goblet cell CL0019031
    CSI 3.59
    rCSI 3.19%
    PRS 97.58
  • M cell of gut CL0000682
    CSI 3.55
    rCSI 3.77%
    PRS 98.49
  • placental villous trophoblast CL2000060
    CSI 3.47
    rCSI 5.36%
    PRS 97.53
  • stem cell CL0000034
    CSI 3.37
    rCSI 3.25%
    PRS 97.76
  • intrahepatic cholangiocyte CL0002538
    CSI 3.2
    rCSI 7.67%
    PRS 97.96
  • club cell CL0000158
    CSI 3.07
    rCSI 4.5%
    PRS 97.47
  • hepatic stellate cell CL0000632
    CSI 2.95
    rCSI 11.03%
    PRS 97.29
  • rod bipolar cell CL0000751
    CSI 2.86
    rCSI 5.13%
    PRS 96.28
  • pancreatic ductal cell CL0002079
    CSI 2.79
    rCSI 5.42%
    PRS 98.19
  • hepatocyte CL0000182
    CSI 2.65
    rCSI 4.74%
    PRS 97
  • paneth cell CL0000510
    CSI 2.63
    rCSI 3.88%
    PRS 99.13
  • periportal region hepatocyte CL0019026
    CSI 2.55
    rCSI 9.9%
    PRS 96.11
  • transit amplifying cell CL0009010
    CSI 2.45
    rCSI 3.75%
    PRS 98.83
  • peripheral nervous system neuron CL2000032
    CSI 2.36
    rCSI 3.21%
    PRS 96.07
  • centrilobular region hepatocyte CL0019029
    CSI 2.35
    rCSI 6.14%
    PRS 95.85
  • epithelial cell of proximal tubule CL0002306
    CSI 2.2
    rCSI 5.37%
    PRS 95.48
  • eye photoreceptor cell CL0000287
    CSI 2.05
    rCSI 23.04%
    PRS 98.17
  • type L enteroendocrine cell CL0002279
    CSI 1.9
    rCSI 3.57%
    PRS 98.23
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.76
    rCSI 4.75%
    PRS 98.68
  • retinal cone cell CL0000573
    CSI 1.7
    rCSI 2.73%
    PRS 95.21
  • cholangiocyte CL1000488
    CSI 1.48
    rCSI 8.87%
    PRS 96.97
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.31
    rCSI 3.66%
    PRS 98.82
  • transit amplifying cell of small intestine CL0009012
    CSI 1.25
    rCSI 5.48%
    PRS 98.79
  • luminal cell of prostate epithelium CL0002340
    CSI 1.04
    rCSI 5.59%
    PRS 98.71
  • type EC enteroendocrine cell CL0000577
    CSI 0.97
    rCSI 3.44%
    PRS 98.07
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.73
    rCSI 11.3%
    PRS 98.19

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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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 [REEP6](/details-gene/92840), or Receptor Expression Enhancing Protein 6, is a protein-coding gene located on chromosome 19p13.3. It functions primarily as a membrane-shaping adapter protein associated with the endoplasmic reticulum ([GO:0005783](https://www.ebi.ac.uk/QuickGO/term/GO:0005783)) and is involved in modulating intracellular protein transport, particularly for G protein-coupled receptors [Link](https://doi.org/10.1371/journal.pone.0076366). Expression data indicates its most significant roles are in specialized epithelial tissues, with particularly high significance in cells of the intestinal lining, such as [intestinal epithelial cell](/details-cell/CL0002563) and [colonocyte](/details-cell/CL1000347). Additionally, [REEP6](/details-gene/92840) plays a critical, well-documented role in vision, where it is essential for the function and survival of [retinal rod cell](/details-cell/CL0000604) [Link](https://doi.org/10.1093/hmg/ddx111). Mutations in this gene are known to cause autosomal-recessive retinitis pigmentosa, a degenerative eye disease [Link](https://doi.org/10.1016/j.ajhg.2016.10.008). ## Cellular Roles and Expression Landscape The expression profile of [REEP6](/details-gene/92840) highlights its importance in cells with high metabolic and secretory activity, particularly within epithelial tissues. **Overall**, the gene shows the highest significance in the gastrointestinal tract. It is a defining marker for [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 14.35), [colonocyte](/details-cell/CL1000347) (CSI: 11.04), and [enterocyte](/details-cell/CL0000584) (CSI: 6.06), which are responsible for nutrient absorption and forming the mucosal barrier. Its high CSI in secretory cell types like [goblet cell](/details-cell/CL0000160) (CSI: 5.06) and [enteroendocrine cell](/details-cell/CL0000164) (CSI: 3.88) suggests a role in managing the trafficking and secretion of mucins and hormones. The gene's significance extends to other epithelial and supportive cells, including [midzonal region hepatocyte](/details-cell/CL0019028) (CSI: 5.59) and [placental villous trophoblast](/details-cell/CL2000060) (CSI: 3.47), underscoring a broad function in protein processing and transport across diverse tissues. A second, highly specialized context for [REEP6](/details-gene/92840) function is in the retina. Its significant expression in [retinal rod cell](/details-cell/CL0000604) (CSI: 3.89) is consistent with its established role in photoreceptor function. Research has demonstrated that [REEP6](/details-gene/92840) is critical for the trafficking of clathrin-coated vesicles and is essential for the survival of these light-sensing cells [Link](https://doi.org/10.1093/hmg/ddx111). ## Pathways and Molecular Function The functions of [REEP6](/details-gene/92840) are primarily centered on protein and vesicle trafficking within the endoplasmic reticulum (ER). Its annotation for '[Endoplasmic reticulum organization](/details-ontology/GO0007029)' and residence in the '[Endoplasmic reticulum membrane](/details-ontology/GO0005789)' are central to its mechanism. As an accessory protein, it facilitates the functional expression of certain receptors, a role that was initially identified for odorant and bitter taste receptors [Link](https://doi.org/10.1016/j.cell.2004.11.021), [Link](https://doi.org/10.1074/jbc.m513637200). Its involvement in '[Regulation of intracellular transport](/details-ontology/GO0032386)' is exemplified by its specific role in photoreceptors. It is directly implicated in the '[Detection of light stimulus involved in visual perception](/details-ontology/GO0050908)' pathway and is a component of the '[Photoreceptor inner segment](/details-ontology/GO0001917)'. Studies indicate that [REEP6](/details-gene/92840) mediates the trafficking of a subset of '[Clathrin-coated vesicle membrane](/details-ontology/GO0030665)' vesicles, a process vital for maintaining photoreceptor structure and function [Link](https://doi.org/10.1093/hmg/ddx111). This molecular function directly explains why loss-of-function mutations lead to retinal degeneration [Link](https://doi.org/10.1016/j.ajhg.2016.10.008). ## Research Directions While the role of [REEP6](/details-gene/92840) in retinal disease is established, its pronounced and specific expression in the intestinal epithelium remains largely unexplored. This presents significant opportunities for future investigation into its function in gut homeostasis and disease. Based on the available data, several testable hypotheses can be proposed: 1. Given its role in GPCR trafficking and high expression in [enteroendocrine cell](/details-cell/CL0000164), [REEP6](/details-gene/92840) is essential for the proper surface expression of nutrient-sensing GPCRs, and its dysfunction may contribute to metabolic disorders by impairing gut hormone secretion. 2. Considering its function in ER organization and its high significance in secretory [goblet cell](/details-cell/CL0000160), [REEP6](/details-gene/92840) may play a protective role in mitigating ER stress associated with high-volume mucin production. Its deficiency could compromise the mucosal barrier and increase susceptibility to inflammatory bowel disease. To test the second hypothesis, a key experiment could involve a CRISPR-Cas9 knockout of [REEP6](/details-gene/92840) in human intestinal organoids. These organoids could then be stimulated to induce mucin hypersecretion (e.g., with a cholinergic agonist) or treated with an ER stressor like tunicamycin. Subsequent RNA-sequencing and proteomic analysis of unfolded protein response (UPR) markers (e.g., BiP, CHOP), combined with immunofluorescence to assess mucin granule formation and secretion, would reveal the gene's role in maintaining secretory cell function under stress. As a therapeutic target, [REEP6](/details-gene/92840) is primarily relevant to loss-of-function pathologies. Its link to a monogenic recessive disorder, retinitis pigmentosa, makes it an ideal candidate for gene replacement therapy, such as AAV-mediated delivery to photoreceptor cells. Inhibition of [REEP6](/details-gene/92840) is unlikely to be a therapeutic strategy. If its role in intestinal diseases is confirmed, strategies aimed at enhancing its expression or function might offer novel treatments for certain forms of inflammatory or metabolic gut disorders.

Genular Protein ID: 2086999020

Symbol: REEP6_HUMAN

Name: Receptor expression-enhancing protein 6

UniProtKB Accession Codes:

Q96HR9 A0A1L5BXV3 B2RE01 D6W5Z0 Q96LM0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 9 Ensembl 2 ExpressionAtlas 1 GO 8 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 2 STRING 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 15550249

Title: RTP family members induce functional expression of mammalian odorant receptors.

PubMed ID: 15550249

DOI: 10.1016/j.cell.2004.11.021

PubMed ID: 27889058

Title: Mutations in REEP6 cause autosomal-recessive retinitis pigmentosa.

PubMed ID: 27889058

DOI: 10.1016/j.ajhg.2016.10.008

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

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: 16720576

Title: Members of RTP and REEP gene families influence functional bitter taste receptor expression.

PubMed ID: 16720576

DOI: 10.1074/jbc.m513637200

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 24098485

Title: REEPs are membrane shaping adapter proteins that modulate specific G protein-coupled receptor trafficking by affecting ER cargo capacity.

PubMed ID: 24098485

DOI: 10.1371/journal.pone.0076366

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 28369466

Title: REEP6 mediates trafficking of a subset of Clathrin-coated vesicles and is critical for rod photoreceptor function and survival.

PubMed ID: 28369466

DOI: 10.1093/hmg/ddx111

PubMed ID: 29120066

Title: A novel nonsense variant in REEP6 is involved in a sporadic rod-cone dystrophy case.

PubMed ID: 29120066

DOI: 10.1111/cge.13171

Sequence Information:

  • Length: 211
  • Mass: 23418
  • Checksum: CB45B084E8A584C9
  • Sequence:
    • MDGLRQRVEH FLEQRNLVTE VLGALEAKTG VEKRYLAAGA VTLLSLYLLF GYGASLLCNL 
IGFVYPAYAS IKAIESPSKD DDTVWLTYWV VYALFGLAEF FSDLLLSWFP FYYVGKCAFL 
LFCMAPRPWN GALMLYQRVV RPLFLRHHGA VDRIMNDLSG RALDAAAGIT RNVLQVLARS 
RAGITPVAVA GPSTPLEADL KPSQTPQPKD K

Genular Protein ID: 3696259397

Symbol: A0A1L5BXV2_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A1L5BXV2

Database IDs:

ARBA 9 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 GO 3 InterPro 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 Pfam 1 RefSeq 1 RuleBase 1 SMR 1 VEuPathDB 1

Citations:

PubMed ID: 27889058

Title: Mutations in REEP6 cause autosomal-recessive retinitis pigmentosa.

PubMed ID: 27889058

DOI: 10.1016/j.ajhg.2016.10.008

Sequence Information:

  • Length: 184
  • Mass: 20733
  • Checksum: 13BE0F61685211CA
  • Sequence:
    • MDGLRQRVEH FLEQRNLVTE VLGALEAKTG VEKRYLAAGA VTLLSLYLLF GYGASLLCNL 
IGFVYPAYAS IKAIESPSKD DDTVWLTYWV VYALFGLAEF FSDLLLSWFP FYYVGKCAFL 
LFCMAPRPWN GALMLYQRVV RPLFLRHHGA VDRIMNDLSG RALDAAAGIT RNVKPSQTPQ 
PKDK