APH1A
Aph-1 homolog A, gamma-secretase subunit
Gene Information Card
| Symbol | APH1A |
|---|---|
| Full Name | Aph-1 homolog A, gamma-secretase subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.2 |
| NCBI Gene ID | 51107 ncbi.nlm.nih.gov/gene/51107 |
| Ensembl ID | ENSG00000161980 |
| UniProt ID | Q96BI3 |
| OMIM ID | 607629 |
| HGNC ID | 24080 |
| Aliases | APH-1A, APH-1, CGI-78, MSTP064, PRO2567 |
Description
APH1A (Aph-1 homolog A, gamma-secretase subunit) is a protein-coding gene that encodes a component of the gamma-secretase complex. This complex is responsible for intramembrane proteolysis of substrates such as amyloid precursor protein (APP) and Notch receptors. APH1A is essential for the assembly and stability of the gamma-secretase complex and plays a critical role in Notch signaling and APP processing. Mutations and altered expression of APH1A have been implicated in Alzheimer disease and other neurodegenerative conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | Altered gamma-secretase activity leads to increased production of amyloid-beta peptides (Aβ42) | ClinVar, OMIM |
| Cerebral amyloid angiopathy | Dysregulated APP cleavage contributes to vascular amyloid deposition | OMIM |
| Notch signaling disorders | Impaired gamma-secretase function disrupts Notch receptor processing | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Heart | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.2 | Neuronal cell line |
| HEK293 | 11.8 | Embryonic kidney cells |
| HeLa | 9.5 | Cervical cancer cells |
| HepG2 | 7.1 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.215C>T (p.Pro72Leu) | Missense | <0.01% | Unknown functional effect; reported in Alzheimer disease cohorts |
| c.388G>A (p.Val130Ile) | Missense | <0.01% | May alter gamma-secretase activity |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in APH1A reduce gamma-secretase complex stability and activity, impairing Notch signaling and APP processing.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Dominant-negative effects have not been described for APH1A.
View complete mutation data：
Gene Ontology (GO)
| • gamma-secretase complex | • aspartic-type endopeptidase activity |
| • intramembrane proteolysis | • Notch signaling pathway |
| • amyloid-beta metabolic process | • membrane |
Pathways
• Alzheimer disease - gamma-secretase pathway
• Notch signaling pathway
• Presenilin-mediated proteolysis
Protein Summary
APH1A is a 308-amino acid transmembrane protein that serves as a scaffold subunit of the gamma-secretase complex. It contains seven transmembrane domains and is essential for the assembly and proteolytic activity of the complex. APH1A interacts with presenilin, nicastrin, and PEN-2 to form the active gamma-secretase holoenzyme. The protein is ubiquitously expressed, with highest levels in brain and neuronal tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APH1A Knockout HEK293 Cell Line | EDJ-KQ51281 | Human | 51107 | Details Get a Quote |
| APH1A Knockout HeLa Cell Line | EDJ-KQ56229 | Human | 51107 | Details Get a Quote |
| APH1A Knockout A-549 Cell Line | EDJ-KQ64719 | Human | 51107 | Details Get a Quote |
| APH1A Knockout HCT 116 Cell Line | EDJ-KQ73164 | Human | 51107 | Details Get a Quote |
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