Details for: RDH5

Gene ID: 5959

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: RDH5

Ensembl ID: ENSG00000135437

Description: retinol dehydrogenase 5

Cell Significance Landscape

Associated with

Significant Cells

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

  • retinal pigment epithelial cell CL0002586
    CSI 9.82
    rCSI 19.49%
    PRS 92.2
  • intestine goblet cell CL0019031
    CSI 3.57
    rCSI 3.17%
    PRS 92.86
  • adipocyte CL0000136
    CSI 3.53
    rCSI 4.54%
    PRS 88.6
  • ON-bipolar cell CL0000749
    CSI 3.47
    rCSI 5.15%
    PRS 93.21
  • perivascular cell CL4033054
    CSI 3.45
    rCSI 4.72%
    PRS 96.67
  • colon epithelial cell CL0011108
    CSI 3.34
    rCSI 3.5%
    PRS 92.81
  • ciliated epithelial cell CL0000067
    CSI 3.27
    rCSI 2.87%
    PRS 88.07
  • stem cell CL0000034
    CSI 2.94
    rCSI 2.83%
    PRS 92.18
  • retinal rod cell CL0000604
    CSI 2.5
    rCSI 4.4%
    PRS 91.5
  • colonocyte CL1000347
    CSI 2.48
    rCSI 3.56%
    PRS 93.02
  • intestinal tuft cell CL0019032
    CSI 2.39
    rCSI 3.65%
    PRS 95.38
  • intestinal epithelial cell CL0002563
    CSI 2.35
    rCSI 2.45%
    PRS 92.88
  • Schwann cell CL0002573
    CSI 2.21
    rCSI 6.29%
    PRS 91.93
  • cardiac muscle cell CL0000746
    CSI 2.12
    rCSI 3.04%
    PRS 88.65
  • vascular associated smooth muscle cell CL0000359
    CSI 1.75
    rCSI 5.67%
    PRS 93.56
  • retinal cone cell CL0000573
    CSI 1.74
    rCSI 2.81%
    PRS 88.69
  • amacrine cell CL0000561
    CSI 1.25
    rCSI 3.61%
    PRS 88.66

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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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [RDH5](/details-gene/5959) (Retinol Dehydrogenase 5) encodes a crucial enzyme belonging to the short-chain dehydrogenase/reductase (SDR) family. Its primary, well-characterized function is as an 11-cis-retinol dehydrogenase, which catalyzes a key step in the visual cycle required for regenerating the visual pigment rhodopsin. This function is critical for [visual perception](/details-go/GO:0007601), particularly in low-light conditions. Consistent with this role, [RDH5](/details-gene/5959) shows exceptionally high and specific expression in the [retinal pigment epithelial cell](/details-cell/CL0002586). Clinically, loss-of-function mutations in [RDH5](/details-gene/5959) are a primary cause of Fundus Albipunctatus ([601617](https://omim.org/entry/601617)), a form of congenital stationary night blindness. While its role in vision is paramount, expression data also suggest secondary roles in other tissues, including the intestinal epithelium and adipose tissue, likely related to broader retinoid and steroid metabolism. ## Cellular Roles and Expression Landscape The expression profile of [RDH5](/details-gene/5959) firmly establishes its identity as a highly specialized gene for retinal function. **Overall**, its significance is overwhelmingly concentrated in the [retinal pigment epithelial cell](/details-cell/CL0002586), which displays a Cell Significance Index (CSI) of 9.82, indicating it is a defining marker for this cell type. This is further supported by significant expression in other retinal cells, including the [ON-bipolar cell](/details-cell/CL0000749) and [retinal rod cell](/details-cell/CL0000604), underscoring its central role in the visual system. Beyond the eye, [RDH5](/details-gene/5959) exhibits a distinct pattern of expression in several other tissues, suggesting broader physiological functions. A notable secondary site of expression is the gastrointestinal tract, with significant CSI scores in [intestine goblet cell](/details-cell/CL0019031), [colon epithelial cell](/details-cell/CL0011108), and [colonocyte](/details-cell/CL1000347). This pattern suggests a potential role in local vitamin A metabolism and retinoic acid signaling within the gut mucosa. Additionally, [RDH5](/details-gene/5959) is significantly expressed in [adipocyte](/details-cell/CL0000136), which may be related to the storage and mobilization of retinoids from fat reserves. Lower but still significant expression in diverse cell types such as [ciliated epithelial cell](/details-cell/CL0000067) and [Schwann cell](/details-cell/CL0002573) hints at more subtle, uncharacterized roles in other biological contexts, a finding supported by reports of its mRNA in extra-ocular tissues ([Link](https://doi.org/10.1042/bj3380023)). ## Pathways and Molecular Function Functionally, [RDH5](/details-gene/5959) is annotated with [11-cis-retinol dehydrogenase activity](/details-go/GO:0106429), a critical catalytic step in the [retinol metabolic process](/details-go/GO:0042572). This activity is central to its function in the eye, where it participates in '[The canonical retinoid cycle in rods (twilight vision)](https://reactome.org/content/detail/R-HSA-2453902)'. This pathway is essential for regenerating 11-cis-retinal, the chromophore of rhodopsin, which is necessary for [visual phototransduction](/details-go/R-HSA-2187338). Consequently, defects in [RDH5](/details-gene/5959) lead to '[Retinoid cycle disease events](https://reactome.org/content/detail/R-HSA-2453864)', manifesting clinically as Fundus Albipunctatus, a disorder characterized by delayed dark adaptation ([Link](https://doi.org/10.1038/9707)). The enzyme localizes to the [endoplasmic reticulum membrane](/details-go/GO:0005789), where it performs this function. Beyond its role in the visual cycle, molecular annotations suggest broader substrate specificity. [RDH5](/details-gene/5959) is also associated with [steroid metabolic process](/details-go/GO:0008202), including [androsterone dehydrogenase activity](/details-go/GO:0047023). This enzymatic promiscuity suggests that in extra-ocular tissues where it is expressed, such as the gut and adipose tissue, [RDH5](/details-gene/5959) may contribute to local steroid hormone metabolism in addition to or instead of retinoid processing. This dual functionality is consistent with findings that have characterized its activity with both steroids and retinoids ([Link](https://doi.org/10.1042/bj3380023)). ## Research Directions While the role of [RDH5](/details-gene/5959) in retinal physiology is well-established, its function in extra-ocular tissues remains largely unexplored. The significant expression in intestinal and adipose cells provides a foundation for new avenues of investigation into its role in metabolism and mucosal biology. Based on the available data, several testable hypotheses can be proposed: 1. In the intestinal epithelium, [RDH5](/details-gene/5959) catalyzes the synthesis of local retinoic acid from dietary retinol, thereby playing a role in modulating mucosal immune tolerance and maintaining the integrity of the epithelial barrier. 2. Within [adipocytes](/details-cell/CL0000136), [RDH5](/details-gene/5959) regulates systemic retinoid availability by converting retinol stored in lipid droplets into signaling molecules that influence adipogenesis and systemic glucose homeostasis. 3. The annotated [androsterone dehydrogenase activity](/details-go/GO:0047023) of [RDH5](/details-gene/5959) is physiologically significant in extra-ocular tissues, where it contributes to the local inactivation or synthesis of androgens, potentially impacting metabolic or inflammatory processes. To test the hypothesis regarding its role in the gut, a key experiment could be proposed. To test the role of [RDH5](/details-gene/5959) in intestinal biology, one could generate and utilize intestinal organoids from *Rdh5*-knockout mice. By supplementing the culture media with retinol, changes in retinoic acid production could be quantified via mass spectrometry, and the expression of retinoic acid-responsive genes could be measured by RNA-seq. This system would allow for a direct assessment of the gene's contribution to local retinoid metabolism independent of systemic influences. From a therapeutic standpoint, [RDH5](/details-gene/5959) is a clear example where functional restoration, not inhibition, is the goal. Since loss-of-function mutations cause retinal disease ([601617](https://omim.org/entry/601617)), therapeutic development is focused on gene replacement strategies. The highly specific expression of [RDH5](/details-gene/5959) in [retinal pigment epithelial cells](/details-cell/CL0002586) makes it an excellent candidate for AAV-mediated gene therapy, as delivery can be targeted directly to the affected cell type, minimizing the risk of off-target effects in tissues where its secondary functions are less critical or understood.

Genular Protein ID: 3645609044

Symbol: RDH5_HUMAN

Name: Retinol dehydrogenase 5

UniProtKB Accession Codes:

Q92781 O00179 Q8TAI2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 26 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EC 3 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 13 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 2 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 2 Rhea 5 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 8884265

Title: Primary structure of human 11-cis retinol dehydrogenase and organization and chromosomal localization of the corresponding gene.

PubMed ID: 8884265

DOI: 10.1006/geno.1996.0487

PubMed ID: 9115228

Title: Identification and characterization of a stereospecific human enzyme that catalyzes 9-cis-retinol oxidation. A possible role in 9-cis-retinoic acid formation.

PubMed ID: 9115228

DOI: 10.1074/jbc.272.18.11744

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: 9931293

Title: Activity of human 11-cis-retinol dehydrogenase (Rdh5) with steroids and retinoids and expression of its mRNA in extra-ocular human tissue.

PubMed ID: 9931293

DOI: 10.1042/bj3380023

PubMed ID: 10588954

Title: Biochemical properties, tissue expression, and gene structure of a short chain dehydrogenase/reductase able to catalyze cis-retinol oxidation.

PubMed ID: 10588954

PubMed ID: 11675386

Title: Biochemical defects in 11-cis-retinol dehydrogenase mutants associated with fundus albipunctatus.

PubMed ID: 11675386

DOI: 10.1074/jbc.m107337200

PubMed ID: 19027726

Title: The SDR (short-chain dehydrogenase/reductase and related enzymes) nomenclature initiative.

PubMed ID: 19027726

DOI: 10.1016/j.cbi.2008.10.040

PubMed ID: 10617778

Title: 11-cis retinol dehydrogenase mutations as a major cause of the congenital night-blindness disorder known as fundus albipunctatus.

PubMed ID: 10617778

PubMed ID: 10369264

Title: Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus.

PubMed ID: 10369264

DOI: 10.1038/9707

PubMed ID: 11078852

Title: A novel compound heterozygous mutation in the RDH5 gene in a patient with fundus albipunctatus.

PubMed ID: 11078852

DOI: 10.1016/s0002-9394(00)00765-0

PubMed ID: 11053295

Title: A high association with cone dystrophy in Fundus albipunctatus caused by mutations of the RDH5 gene.

PubMed ID: 11053295

PubMed ID: 11053296

Title: Mutations in the 11-cis retinol dehydrogenase gene in Japanese patients with Fundus albipunctatus.

PubMed ID: 11053296

PubMed ID: 11470705

Title: Null mutation in the human 11-cis retinol dehydrogenase gene associated with fundus albipunctatus.

PubMed ID: 11470705

DOI: 10.1016/s0161-6420(01)00640-6

PubMed ID: 12788147

Title: Macular dystrophy in a Japanese family with fundus albipunctatus.

PubMed ID: 12788147

DOI: 10.1016/s0002-9394(02)02290-0

PubMed ID: 12967826

Title: A novel RDH5 gene mutation in a patient with fundus albipunctatus presenting with macular atrophy and fading white dots.

PubMed ID: 12967826

DOI: 10.1016/s0002-9394(03)00332-5

PubMed ID: 22736946

Title: Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous Pakistani families.

PubMed ID: 22736946

PubMed ID: 24603341

Title: exomeSuite: Whole exome sequence variant filtering tool for rapid identification of putative disease causing SNVs/indels.

PubMed ID: 24603341

DOI: 10.1016/j.ygeno.2014.02.006

PubMed ID: 25820994

Title: Fundus albipunctatus: review of the literature and report of a novel RDH5 gene mutation affecting the invariant tyrosine (p.Tyr175Phe).

PubMed ID: 25820994

DOI: 10.1007/s13353-015-0281-x

PubMed ID: 28418496

Title: Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families.

PubMed ID: 28418496

DOI: 10.1167/iovs.17-21424

PubMed ID: 29541409

Title: Inhibition of dihydrotestosterone synthesis in prostate cancer by combined frontdoor and backdoor pathway blockade.

PubMed ID: 29541409

DOI: 10.18632/oncotarget.24107

Sequence Information:

  • Length: 318
  • Mass: 34979
  • Checksum: 2CE24343F2EEA4B7
  • Sequence:
    • MWLPLLLGAL LWAVLWLLRD RQSLPASNAF VFITGCDSGF GRLLALQLDQ RGFRVLASCL 
TPSGAEDLQR VASSRLHTTL LDITDPQSVQ QAAKWVEMHV KEAGLFGLVN NAGVAGIIGP 
TPWLTRDDFQ RVLNVNTMGP IGVTLALLPL LQQARGRVIN ITSVLGRLAA NGGGYCVSKF 
GLEAFSDSLR RDVAHFGIRV SIVEPGFFRT PVTNLESLEK TLQACWARLP PATQAHYGGA 
FLTKYLKMQQ RIMNLICDPD LTKVSRCLEH ALTARHPRTR YSPGWDAKLL WLPASYLPAS 
LVDAVLTWVL PKPAQAVY