Details for: SORD

Gene ID: 6652

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: SORD

Ensembl ID: ENSG00000140263

Description: sorbitol dehydrogenase

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • duct epithelial cell CL0000068
    CSI 8.38
    rCSI 12.25%
    PRS 93.51
  • common dendritic progenitor CL0001029
    CSI 7.32
    rCSI 9.19%
    PRS 94.94
  • centrilobular region hepatocyte CL0019029
    CSI 6.38
    rCSI 16.64%
    PRS 86.45
  • epithelial cell of proximal tubule CL0002306
    CSI 5.55
    rCSI 13.57%
    PRS 83.84
  • tracheal goblet cell CL1000329
    CSI 4.77
    rCSI 10.41%
    PRS 92.55
  • Kupffer cell CL0000091
    CSI 4.37
    rCSI 10%
    PRS 91.44
  • secretory cell CL0000151
    CSI 3.63
    rCSI 3.79%
    PRS 89.2
  • intestinal epithelial cell CL0002563
    CSI 3.61
    rCSI 3.78%
    PRS 87.94
  • intestine goblet cell CL0019031
    CSI 3.32
    rCSI 2.95%
    PRS 87.85
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.32
    rCSI 3%
    PRS 89.07
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.31
    rCSI 2.57%
    PRS 92.77
  • epithelial cell of lung CL0000082
    CSI 3.25
    rCSI 2.7%
    PRS 91.13
  • midzonal region hepatocyte CL0019028
    CSI 3.2
    rCSI 7.5%
    PRS 88.12
  • common myeloid progenitor CL0000049
    CSI 3.12
    rCSI 2.52%
    PRS 91.55
  • pancreatic D cell CL0000173
    CSI 3.11
    rCSI 3.06%
    PRS 91.97
  • nasal mucosa goblet cell CL0002480
    CSI 3.1
    rCSI 3.6%
    PRS 90.78
  • goblet cell CL0000160
    CSI 3.04
    rCSI 2.88%
    PRS 88.15
  • pancreatic A cell CL0000171
    CSI 3.03
    rCSI 3.18%
    PRS 92.1
  • hepatic stellate cell CL0000632
    CSI 2.95
    rCSI 11.04%
    PRS 85.75
  • paneth cell CL0000510
    CSI 2.88
    rCSI 4.25%
    PRS 95.21
  • club cell CL0000158
    CSI 2.85
    rCSI 4.18%
    PRS 85.82
  • keratinocyte CL0000312
    CSI 2.74
    rCSI 2.3%
    PRS 90.66
  • luminal cell of prostate epithelium CL0002340
    CSI 2.74
    rCSI 14.74%
    PRS 94.06
  • ciliated cell CL0000064
    CSI 2.74
    rCSI 4.44%
    PRS 84.67
  • neural crest cell CL0011012
    CSI 2.71
    rCSI 2.14%
    PRS 83.38
  • hematopoietic stem cell CL0000037
    CSI 2.7
    rCSI 1.8%
    PRS 91.73
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.56
    rCSI 2.21%
    PRS 92.32
  • ciliated epithelial cell CL0000067
    CSI 2.55
    rCSI 2.24%
    PRS 81.82
  • acinar cell CL0000622
    CSI 2.49
    rCSI 3.66%
    PRS 95.12
  • stem cell CL0000034
    CSI 2.37
    rCSI 2.29%
    PRS 86.27
  • pancreatic acinar cell CL0002064
    CSI 2.33
    rCSI 3.1%
    PRS 93.09
  • ionocyte CL0005006
    CSI 2.27
    rCSI 2.44%
    PRS 91.62
  • periportal region hepatocyte CL0019026
    CSI 2.24
    rCSI 8.71%
    PRS 87.43
  • mucous neck cell CL0000651
    CSI 2.24
    rCSI 3.22%
    PRS 92.82
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.22
    rCSI 4.88%
    PRS 93.24
  • multi-ciliated epithelial cell CL0005012
    CSI 2.21
    rCSI 2.21%
    PRS 84.89
  • conjunctival epithelial cell CL1000432
    CSI 2.18
    rCSI 3.34%
    PRS 89.6
  • respiratory suprabasal cell CL4033048
    CSI 2.18
    rCSI 2.79%
    PRS 91.98
  • hepatocyte CL0000182
    CSI 2.14
    rCSI 3.83%
    PRS 89.08
  • enteroendocrine cell CL0000164
    CSI 2.12
    rCSI 2.9%
    PRS 88.89
  • M cell of gut CL0000682
    CSI 2.11
    rCSI 2.24%
    PRS 92.35
  • foveolar cell of stomach CL0002179
    CSI 2.07
    rCSI 4.4%
    PRS 92.35
  • respiratory basal cell CL0002633
    CSI 2.05
    rCSI 2.12%
    PRS 91.9
  • renal interstitial pericyte CL1001318
    CSI 1.98
    rCSI 5.46%
    PRS 87.7
  • colon epithelial cell CL0011108
    CSI 1.86
    rCSI 1.95%
    PRS 88.06
  • kidney epithelial cell CL0002518
    CSI 1.84
    rCSI 3.51%
    PRS 96.63
  • lung ciliated cell CL1000271
    CSI 1.81
    rCSI 2.1%
    PRS 84.91
  • peripheral nervous system neuron CL2000032
    CSI 1.77
    rCSI 2.41%
    PRS 84.05
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.73
    rCSI 4.38%
    PRS 84.12
  • squamous epithelial cell CL0000076
    CSI 1.72
    rCSI 4.07%
    PRS 87.68
  • glandular epithelial cell CL0000150
    CSI 1.64
    rCSI 4.33%
    PRS 96.1
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.63
    rCSI 1.57%
    PRS 88.91
  • type L enteroendocrine cell CL0002279
    CSI 1.36
    rCSI 2.56%
    PRS 92.33
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 1.3
    rCSI 10.33%
    PRS 86.16
  • mammary gland epithelial cell CL0002327
    CSI 1.16
    rCSI 4.08%
    PRS 93.99
  • respiratory goblet cell CL0002370
    CSI 1.05
    rCSI 11.46%
    PRS 92.98
  • forebrain radial glial cell CL0013000
    CSI 1
    rCSI 3.21%
    PRS 90.16
  • bronchial goblet cell CL1000312
    CSI 0.98
    rCSI 3.93%
    PRS 93.29
  • pancreatic ductal cell CL0002079
    CSI 0.98
    rCSI 1.9%
    PRS 91.84
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 0.83
    rCSI 1.9%
    PRS 83.59
  • type EC enteroendocrine cell CL0000577
    CSI 0.77
    rCSI 2.74%
    PRS 91.59
  • enteroendocrine cell of colon CL0009042
    CSI 0.68
    rCSI 3.2%
    PRS 92.55
  • tracheobronchial serous cell CL0019001
    CSI 0.62
    rCSI 2.69%
    PRS 92.56
  • basal cell of epithelium of trachea CL1000348
    CSI 0.62
    rCSI 4.36%
    PRS 90.89
  • erythroid progenitor cell CL0000038
    CSI 0.5
    rCSI 2.87%
    PRS 92.43
  • epithelial cell of urethra CL1000296
    CSI 0.21
    rCSI 5.28%
    PRS 92.85

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 [SORD](/details-gene/6652) encodes sorbitol dehydrogenase, a cytosolic enzyme that catalyzes the NAD-dependent conversion of sorbitol to fructose. This reaction is the second and final step in the polyol pathway, a metabolic route that processes glucose into fructose. As a key component of carbohydrate metabolism, particularly fructose biosynthesis ([R-HSA-5652227](https://reactome.org/content/detail/R-HSA-5652227)), [SORD](/details-gene/6652) is crucial for managing polyol levels in various tissues. Its expression is particularly significant in epithelial cells of secretory and metabolic organs, such as the liver ([centrilobular region hepatocyte](/details-cell/CL0019029)) and kidney ([epithelial cell of proximal tubule](/details-cell/CL0002306)), as well as in certain hematopoietic progenitors. Genetic variants and dysregulation of [SORD](/details-gene/6652) are associated with human health, including a potential link to diabetic complications ([Link](https://doi.org/10.1155/2014/801269)) and an entry in OMIM ([182500](https://omim.org/entry/182500)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [SORD](/details-gene/6652) highlights its central role in metabolically active and specialized epithelial tissues. The gene shows the highest significance in [duct epithelial cell](/details-cell/CL0000068) (CSI: 8.38), suggesting a key function in glandular and secretory tissues. This is further supported by its high significance in [epithelial cell of proximal tubule](/details-cell/CL0002306) in the kidney, and various respiratory epithelial cells, including [tracheal goblet cell](/details-cell/CL1000329) and [epithelial cell of lower respiratory tract](/details-cell/CL0002632). A second major site of [SORD](/details-gene/6652) activity is the liver, with high significance in [centrilobular region hepatocyte](/details-cell/CL0019029), [Kupffer cell](/details-cell/CL0000091), and [midzonal region hepatocyte](/details-cell/CL0019028). This pattern is consistent with the liver's role as a primary site of fructose metabolism. Interestingly, [SORD](/details-gene/6652) also appears significant in several hematopoietic progenitor populations, including [common dendritic progenitor](/details-cell/CL0001029), [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), and [common myeloid progenitor](/details-cell/CL0000049). This suggests a potential role for the polyol pathway in the metabolic programming and differentiation of early blood cells. ## Pathways and Molecular Function [SORD](/details-gene/6652) functions as an L-iditol 2-dehydrogenase, primarily involved in carbohydrate metabolism ([R-HSA-71387](https://reactome.org/content/detail/R-HSA-71387)). Its core function is the [sorbitol catabolic process](/details-go/GO:0006062), converting sorbitol into fructose as part of the [Fructose biosynthesis](/details-go/GO:0046370) pathway. This enzymatic activity requires [NAD binding](/details-go/GO:0051287) and [zinc ion binding](/details-go/GO:0008270) for catalytic function. The functional annotations align well with its expression landscape. Its involvement in fructose and glucose metabolic processes ([GO:0006006](https://www.ebi.ac.uk/QuickGO/term/GO:0006006)) is consistent with its high expression in hepatocytes and kidney tubular cells, which are key sites for glucose homeostasis and metabolite processing. A specific annotation for [flagellated sperm motility](/details-go/GO:0030317) is also noteworthy and is supported by research demonstrating the activity of the polyol pathway in human semen ([Link](https://doi.org/10.2164/jandrol.05108)). The enzyme primarily resides in the [cytosol](/details-go/GO:0005829), though it has also been detected in the [extracellular space](/details-go/GO:0005615). ## Research Directions The role of the polyol pathway, and [SORD](/details-gene/6652) by extension, in the pathophysiology of diabetic complications is an area of intense research. Hyperglycemia leads to increased flux through this pathway, causing accumulation of sorbitol and fructose, which in turn can lead to osmotic stress, oxidative stress, and the formation of advanced glycation end products. Based on its cellular expression and function, several testable hypotheses can be proposed: 1. Given its high significance in diverse epithelial cell types ([duct epithelial cell](/details-cell/CL0000068), [epithelial cell of proximal tubule](/details-cell/CL0002306)), [SORD](/details-gene/6652) acts as a critical regulator of intracellular osmolarity under hyperglycemic conditions. Its dysfunction or saturation may directly contribute to the cellular damage seen in diabetic nephropathy and other epithelial pathologies by failing to process excess sorbitol. 2. The high significance of [SORD](/details-gene/6652) in hematopoietic progenitors ([common dendritic progenitor](/details-cell/CL0001029), [common myeloid progenitor](/details-cell/CL0000049)) suggests that fructose metabolism via the polyol pathway is essential for the metabolic reprogramming required for myeloid lineage commitment. Dysregulation of [SORD](/details-gene/6652) in these progenitors under metabolic stress could skew differentiation outcomes and impair immune cell development. **Experimental Proposal:** To test the first hypothesis regarding its role in epithelial stress, a robust experiment could involve CRISPR-Cas9-mediated knockout of [SORD](/details-gene/6652) in a human proximal tubule kidney cell line (e.g., HK-2). These knockout cells, alongside wild-type controls, would be cultured under normal glucose (5 mM) and chronic high glucose (25 mM) conditions. The impact could be assessed by measuring intracellular sorbitol and fructose levels using liquid chromatography-mass spectrometry (LC-MS), evaluating cellular viability and apoptosis (e.g., via Annexin V staining and flow cytometry), and quantifying markers of oxidative stress (e.g., reactive oxygen species production). This would directly test whether [SORD](/details-gene/6652) is necessary to protect renal epithelial cells from glucose-induced toxicity. **Therapeutic Potential:** As an enzyme central to a pathway implicated in diabetic complications, [SORD](/details-gene/6652) is a plausible therapeutic target. **Inhibition** of [SORD](/details-gene/6652) could be a strategy to prevent the downstream consequences of polyol pathway activation, such as the generation of fructose and subsequent metabolic stress. While the upstream enzyme, aldose reductase, is often considered the primary target to prevent sorbitol accumulation, [SORD](/details-gene/6652) inhibitors could offer a complementary approach, particularly in tissues where it is highly expressed and fructose-mediated damage is a key pathogenic driver. Such inhibitors would need to be highly specific to avoid off-target effects on other dehydrogenases.

Genular Protein ID: 896862684

Symbol: DHSO_HUMAN

Name: L-iditol 2-dehydrogenase

UniProtKB Accession Codes:

Q00796 B2R655 B7Z3A6 J3JZZ5 Q16682 Q9UMD6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 39 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EC 4 EMBL 22 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 22 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 REPRODUCTION-2DPAGE 1 RNAct 1 Reactome 2 RefSeq 1 Rhea 7 SABIO-RK 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8088829

Title: The human sorbitol dehydrogenase gene: cDNA cloning, sequence determination, and mapping by fluorescence in situ hybridization.

PubMed ID: 8088829

DOI: 10.1006/geno.1994.1276

PubMed ID: 7782086

Title: Structural organization of the human sorbitol dehydrogenase gene (SORD).

PubMed ID: 7782086

DOI: 10.1016/0888-7543(95)80082-w

PubMed ID: 9183016

Title: Identification and characterisation of a sequence related to human sorbitol dehydrogenase.

PubMed ID: 9183016

DOI: 10.1111/j.1432-1033.1997.00760.x

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 2691249

Title: Variability within mammalian sorbitol dehydrogenases. The primary structure of the human liver enzyme.

PubMed ID: 2691249

DOI: 10.1111/j.1432-1033.1989.tb15240.x

PubMed ID: 12665801

Title: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.

PubMed ID: 12665801

DOI: 10.1038/nbt810

PubMed ID: 3365415

Title: Purification and characterization of human liver sorbitol dehydrogenase.

PubMed ID: 3365415

DOI: 10.1021/bi00405a035

PubMed ID: 16278369

Title: Polyol pathway in human epididymis and semen.

PubMed ID: 16278369

DOI: 10.2164/jandrol.05108

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 20372835

Title: Sorbitol dehydrogenase expression is regulated by androgens in the human prostate.

PubMed ID: 20372835

DOI: 10.3892/or_00000755

PubMed ID: 19423711

Title: ZAC1 is up-regulated by hypertonicity and decreases sorbitol dehydrogenase expression, allowing accumulation of sorbitol in kidney cells.

PubMed ID: 19423711

DOI: 10.1074/jbc.m109.001792

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 25105142

Title: Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets.

PubMed ID: 25105142

DOI: 10.1155/2014/801269

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25944712

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

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 29966615

Title: Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets.

PubMed ID: 29966615

DOI: 10.1016/j.ejphar.2018.06.034

PubMed ID: 12962626

Title: X-ray crystallographic and kinetic studies of human sorbitol dehydrogenase.

PubMed ID: 12962626

DOI: 10.1016/s0969-2126(03)00167-9

PubMed ID: 32367058

Title: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.

PubMed ID: 32367058

DOI: 10.1038/s41588-020-0615-4

PubMed ID: 32457452

Title:

PubMed ID: 32457452

DOI: 10.1038/s41588-020-0649-7

PubMed ID: 33314640

Title: Evaluation of SORD mutations as a novel cause of Charcot-Marie-Tooth disease.

PubMed ID: 33314640

DOI: 10.1002/acn3.51268

PubMed ID: 33397963

Title: Biallelic SORD pathogenic variants cause Chinese patients with distal hereditary motor neuropathy.

PubMed ID: 33397963

DOI: 10.1038/s41525-020-00165-6

Sequence Information:

  • Length: 357
  • Mass: 38325
  • Checksum: FF13DDD5EBE47754
  • Sequence:
    • MAAAAKPNNL SLVVHGPGDL RLENYPIPEP GPNEVLLRMH SVGICGSDVH YWEYGRIGNF 
IVKKPMVLGH EASGTVEKVG SSVKHLKPGD RVAIEPGAPR ENDEFCKMGR YNLSPSIFFC 
ATPPDDGNLC RFYKHNAAFC YKLPDNVTFE EGALIEPLSV GIHACRRGGV TLGHKVLVCG 
AGPIGMVTLL VAKAMGAAQV VVTDLSATRL SKAKEIGADL VLQISKESPQ EIARKVEGQL 
GCKPEVTIEC TGAEASIQAG IYATRSGGNL VLVGLGSEMT TVPLLHAAIR EVDIKGVFRY 
CNTWPVAISM LASKSVNVKP LVTHRFPLEK ALEAFETFKK GLGLKIMLKC DPSDQNP