ASPH (Aspartate Beta-Hydroxylase) Gene
A comprehensive overview of the ASPH gene, its function, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | ASPH |
|---|---|
| Full Name | Aspartate Beta-Hydroxylase |
| Gene Type | Protein coding |
| Chromosomal Location | 8q12.1 |
| NCBI Gene ID | 444 ncbi.nlm.nih.gov/gene/444 |
| Ensembl ID | ENSG00000198355 |
| UniProt ID | Q12797 |
| OMIM ID | 600582 |
| HGNC ID | 757 |
| Aliases | BAH, FDLAB, HAAH, junctin |
Description
The ASPH gene encodes aspartate beta-hydroxylase, an enzyme that catalyzes the hydroxylation of aspartic acid and asparagine residues in epidermal growth factor (EGF)-like domains of proteins. This post-translational modification is crucial for the proper folding and function of several proteins, including those involved in calcium binding and cell signaling. ASPH is widely expressed in various tissues and has been implicated in multiple cellular processes, including cell migration, proliferation, and differentiation. Notably, ASPH is overexpressed in several cancers and is considered a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of ASPH promotes tumor growth, invasion, and metastasis through enhanced Notch signaling and altered calcium homeostasis. | High expression in hepatocellular carcinoma, breast cancer, colon cancer, and others; associated with poor prognosis. |
| Facial Dysmorphism, Lethal, with Abdominal Calcification (FDLAB) | Biallelic loss-of-function mutations in ASPH lead to severe developmental defects, including facial dysmorphism and abdominal calcifications. | OMIM #601095; rare autosomal recessive disorder. |
| Alzheimer's Disease | ASPH expression is elevated in brain regions affected by Alzheimer's disease, potentially contributing to amyloid-beta toxicity. | Increased ASPH immunoreactivity in hippocampal neurons of AD patients. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Liver | High | High |
| Kidney | Medium | Medium |
| Heart | Medium | Medium |
| Lung | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | High | Overexpressed in hepatocellular carcinoma cell lines |
| MCF7 (breast cancer) | High | Overexpressed in breast cancer cell lines |
| A549 (lung cancer) | Medium | Moderate expression in lung cancer cells |
| HEK293 (embryonic kidney) | Low | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare | Loss of function; associated with FDLAB |
| c.1567G>A (p.Gly523Arg) | Missense | Rare | Loss of function; associated with FDLAB |
| c.2104A>G (p.Thr702Ala) | Missense | Common polymorphism | No known functional effect |
| c.2345C>T (p.Pro782Leu) | Missense | Rare | Potential impact on enzyme activity; not well characterized |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., nonsense, frameshift) cause FDLAB, a severe developmental disorder. Loss of ASPH activity disrupts hydroxylation of EGF domains, leading to impaired protein function.
Gain of Function (GOF)
Overexpression of wild-type ASPH in cancers acts as a gain-of-function, promoting oncogenic signaling pathways, particularly Notch, and enhancing tumor progression.
Dominant Negative (DN)
No clear dominant-negative mutations have been reported for ASPH. However, some missense variants may exert a dominant-negative effect by interfering with dimerization, but this is speculative.
View complete mutation data：
Gene Ontology (GO)
| • Aspartate beta-hydroxylase activity | • Calcium ion binding |
| • Oxidoreductase activity | • Endoplasmic reticulum lumen |
| • Integral component of membrane | • Protein modification process |
Pathways
• Notch signaling pathway
• Protein hydroxylation
• Calcium signaling
Protein Summary
The ASPH protein is a type II transmembrane protein localized to the endoplasmic reticulum (ER) membrane. It contains an N-terminal cytoplasmic domain, a transmembrane region, and a large C-terminal catalytic domain facing the ER lumen. The enzyme requires Fe2+ and 2-oxoglutarate as cofactors to hydroxylate aspartic acid and asparagine residues in EGF-like domains. This modification is essential for the proper folding and calcium-binding properties of target proteins. ASPH also exists as soluble isoforms due to alternative splicing, which may have distinct functions. In cancer, ASPH overexpression enhances cell motility and invasion, partly through activation of the Notch pathway.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ASPH Knockout HEK293 Cell Line | EDJ-KQ1581 | Human | 444 | Details Get a Quote |
| ASPHD1 Knockout HEK293 Cell Line | EDJ-KQ11750 | Human | 253982 | Details Get a Quote |
| ASPHD2 Knockout HEK293 Cell Line | EDJ-KQ12459 | Human | 57168 | Details Get a Quote |
| ASPHD1 Knockout A-549 Cell Line | EDJ-KQ40132 | Human | 253982 | Details Get a Quote |
| ASPHD1 Knockout HCT 116 Cell Line | EDJ-KQ40133 | Human | 253982 | Details Get a Quote |
| ASPHD1 Knockout HeLa Cell Line | EDJ-KQ40134 | Human | 253982 | Details Get a Quote |
| ASPHD2 Knockout A-549 Cell Line | EDJ-KQ41396 | Human | 57168 | Details Get a Quote |
| ASPHD2 Knockout HCT 116 Cell Line | EDJ-KQ41397 | Human | 57168 | Details Get a Quote |
| ASPH Knockout A-549 Cell Line | EDJ-KQ21264 | Human | 444 | Details Get a Quote |
| ASPH Knockout HCT 116 Cell Line | EDJ-KQ21265 | Human | 444 | Details Get a Quote |
| ASPH Knockout HeLa Cell Line | EDJ-KQ21266 | Human | 444 | Details Get a Quote |
| ASPHD2 Knockout HeLa Cell Line | EDJ-KQ56818 | Human | 57168 | Details Get a Quote |
