SORD Gene (Sorbitol Dehydrogenase)
Genetic and Functional Insights into SORD Deficiency and Related Disorders
Gene Information Card
| Symbol | SORD |
|---|---|
| Full Name | Sorbitol Dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.1 |
| NCBI Gene ID | 6652 ncbi.nlm.nih.gov/gene/6652 |
| Ensembl ID | ENSG00000140284 |
| UniProt ID | Q00796 |
| OMIM ID | 182500 |
| HGNC ID | 11184 |
| Aliases | SORD1, SDH, SORD2 |
Description
The SORD gene encodes sorbitol dehydrogenase (SDH), an enzyme that catalyzes the interconversion of sorbitol to fructose using NAD+ as a cofactor. This reaction is the second step of the polyol pathway, which plays a role in glucose metabolism and osmotic regulation. Loss-of-function mutations in SORD cause autosomal recessive SORD deficiency, a recently identified cause of hereditary peripheral neuropathy (Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| SORD deficiency (Charcot-Marie-Tooth disease type 2) | Loss-of-function mutations impair sorbitol-to-fructose conversion, leading to sorbitol accumulation and axonal degeneration. | ClinVar, OMIM |
| Distal hereditary motor neuropathy (dHMN) | Same mechanism as above; biallelic SORD mutations result in motor neuron dysfunction. | ClinVar, OMIM |
| Diabetic neuropathy (susceptibility) | Altered polyol pathway activity may contribute to sorbitol accumulation in hyperglycemic states. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Nerve (tibial) | 6.1 | Medium |
| Heart | 4.2 | Low |
| Skeletal muscle | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 9.7 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 5.4 | Moderate expression |
| A549 (lung) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.757delG (p.Ala253Glnfs*27) | Frameshift | Common in European and Asian populations | Loss of function |
| c.458C>A (p.Ala153Asp) | Missense | Rare | Loss of function |
| c.716G>A (p.Arg239His) | Missense | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., frameshift, nonsense, missense) cause SORD deficiency, leading to sorbitol accumulation and peripheral neuropathy.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • sorbitol dehydrogenase activity (GO:0003938) | • oxidation-reduction process (GO:0055114) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
Pathways
• Polyol pathway (sorbitol to fructose conversion)
• Fructose and mannose metabolism
Protein Summary
Sorbitol dehydrogenase (SDH) is a homotetrameric enzyme that catalyzes the NAD+-dependent oxidation of sorbitol to fructose. It is highly expressed in liver and kidney, with moderate expression in peripheral nerve tissue. The enzyme is critical for the polyol pathway; its deficiency leads to sorbitol accumulation, which is toxic to Schwann cells and neurons, resulting in axonal neuropathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SORD Knockout HEK293 Cell Line | EDJ-KQ5821 | Human | 6652 | Details Get a Quote |
| SORD Knockout A-549 Cell Line | EDJ-KQ29253 | Human | 6652 | Details Get a Quote |
| SORD Knockout HCT 116 Cell Line | EDJ-KQ29254 | Human | 6652 | Details Get a Quote |
| SORD Knockout HeLa Cell Line | EDJ-KQ29255 | Human | 6652 | Details Get a Quote |
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