CHDH Gene (Choline Dehydrogenase): Function, Disease Associations, and Expression
Explore the CHDH gene, its role in choline metabolism, associated diseases, tissue expression, and mutations.
Gene Information Card
| Symbol | CHDH |
|---|---|
| Full Name | Choline dehydrogenase |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 55351 ncbi.nlm.nih.gov/gene/55351 |
| Ensembl ID | ENSG00000116337 |
| UniProt ID | Q8NE62 |
| OMIM ID | 606081 |
| HGNC ID | 19117 |
| Aliases | CHD, DKFZp686H1320 |
Description
The CHDH gene encodes choline dehydrogenase, a mitochondrial enzyme that catalyzes the oxidation of choline to betaine aldehyde, the first step in the biosynthesis of glycine betaine. This enzyme plays a critical role in choline metabolism, which is essential for phospholipid synthesis, methyl group donation, and osmoregulation. CHDH is expressed in various tissues, with highest levels in liver and kidney. Mutations in CHDH have been associated with susceptibility to neural tube defects and non-alcoholic fatty liver disease (NAFLD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neural tube defects (NTDs) | CHDH variants may impair choline oxidation, leading to reduced betaine availability and altered methylation, which is critical for neural tube closure. | ClinVar, PMID: 19129172 |
| Non-alcoholic fatty liver disease (NAFLD) | CHDH deficiency reduces phosphatidylcholine synthesis, leading to lipid accumulation in hepatocytes. | ClinVar, PMID: 20558524 |
| Choline deficiency | Loss-of-function mutations reduce choline oxidation, exacerbating choline deficiency symptoms. | UniProt, PMID: 15634671 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.4 | High |
| Kidney | 8.7 | Medium |
| Brain | 2.1 | Low |
| Heart | 1.5 | Low |
| Skeletal muscle | 0.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Liver cancer cell line, high expression |
| HEK293 | 3.4 | Embryonic kidney, moderate |
| A549 | 1.2 | Lung carcinoma, low |
| MCF7 | 0.5 | Breast cancer, very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs12676 (c.940G>A, p.Val314Ile) | Missense | ~15% in European populations | Reduced enzyme activity, associated with NTD risk |
| rs9001 (c.1195C>T, p.Pro399Ser) | Missense | ~5% in Asian populations | Impaired choline oxidation, linked to NAFLD |
| c.424G>A (p.Gly142Arg) | Missense | Rare | Loss of function, severe choline deficiency |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Gly142Arg result in complete loss of enzymatic activity, leading to choline oxidation deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CHDH.
Dominant Negative (DN)
No dominant-negative effects have been described; CHDH mutations are typically recessive or act as risk factors.
View complete mutation data：
Gene Ontology (GO)
| • Choline dehydrogenase activity (GO:0008812) | • Oxidoreductase activity (GO:0016491) |
| • Mitochondrion (GO:0005739) | • Choline metabolic process (GO:0019287) |
| • Betaine biosynthetic process (GO:0019288) |
Pathways
• Glycine betaine biosynthesis (Reactome: R-HSA-6798163)
• Choline metabolism (KEGG: map00564)
• Methionine metabolism (KEGG: map00270)
Protein Summary
Choline dehydrogenase is a 594-amino acid mitochondrial flavoprotein that catalyzes the conversion of choline to betaine aldehyde using FAD as a cofactor. The protein is anchored to the inner mitochondrial membrane and forms a homodimer. It is highly expressed in liver and kidney, where it regulates choline homeostasis. Structural studies show a conserved FAD-binding domain and a substrate-binding pocket. Post-translational modifications include phosphorylation, which may modulate activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CHDH Knockout HEK293 Cell Line | EDJ-KQ12909 | Human | 55349 | Details Get a Quote |
| CHDH Knockout A-549 Cell Line | EDJ-KQ42101 | Human | 55349 | Details Get a Quote |
| CHDH Knockout HeLa Cell Line | EDJ-KQ42103 | Human | 55349 | Details Get a Quote |
| CHDH Knockout HCT 116 Cell Line | EDJ-KQ40850 | Human | 55349 | Details Get a Quote |
