APH1B
Aph-1 homolog B, gamma-secretase subunit
Gene Information Card
| Symbol | APH1B |
|---|---|
| Full Name | Aph-1 homolog B, gamma-secretase subunit |
| Gene Type | protein-coding |
| Chromosomal Location | 15q22.2 |
| NCBI Gene ID | 83464 ncbi.nlm.nih.gov/gene/83464 |
| Ensembl ID | ENSG00000137807 |
| UniProt ID | Q8WW43 |
| OMIM ID | 607630 |
| HGNC ID | 24080 |
| Aliases | APH-1B, PSFL, PRO1354 |
Description
APH1B encodes a component of the gamma-secretase complex, which cleaves integral membrane proteins such as Notch receptors and amyloid precursor protein (APP). The complex is composed of presenilin (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B), and PEN2 (PSENEN). APH1B is one of two human APH1 paralogs and is essential for complex assembly and proteolytic activity. Mutations or altered expression of APH1B have been implicated in Alzheimer disease and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | Altered gamma-secretase activity may increase Aβ42/Aβ40 ratio; APH1B variants modulate risk | ClinVar, OMIM |
| Cerebral amyloid angiopathy | Dysregulated APP processing via gamma-secretase | ClinVar |
| Notch signaling disorders | Impaired Notch cleavage due to gamma-secretase dysfunction | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Heart | 7.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.0 | Neuroblastoma cell line |
| HEK293 | 11.2 | Embryonic kidney cells |
| HeLa | 9.8 | Cervical carcinoma cells |
| MCF7 | 7.5 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Likely loss of start codon; ClinVar |
| c.200C>T (p.Thr67Ile) | missense | <0.01% | Uncertain significance; ClinVar |
| c.400G>A (p.Glu134Lys) | missense | <0.01% | Uncertain significance; ClinVar |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in APH1B impair gamma-secretase assembly and reduce Notch/APP cleavage.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Dominant-negative effects have not been described for APH1B.
View complete mutation data：
Gene Ontology (GO)
| • endopeptidase activity | • gamma-secretase complex |
| • membrane | • Notch signaling pathway |
| • amyloid-beta metabolic process | • protein processing |
Pathways
• Alzheimer disease (KEGG: hsa05010)
• Notch signaling (KEGG: hsa04330)
• Gamma-secretase complex (Reactome: R-HSA-157906)
Protein Summary
APH1B is a 257-amino acid multi-pass transmembrane protein that serves as a stabilizing scaffold within the gamma-secretase complex. It contains seven transmembrane domains and is localized to the endoplasmic reticulum, Golgi, and plasma membrane. APH1B is required for the proteolytic maturation of nicastrin and the endoproteolysis of presenilin, enabling the complex to cleave substrates such as APP and Notch. Its expression is ubiquitous but highest in brain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APH1B Knockout HEK293 Cell Line | EDJ-KQ3702 | Human | 83464 | Details Get a Quote |
| APH1B Knockout A-549 Cell Line | EDJ-KQ25718 | Human | 83464 | Details Get a Quote |
| APH1B Knockout HCT 116 Cell Line | EDJ-KQ25719 | Human | 83464 | Details Get a Quote |
| APH1B Knockout HeLa Cell Line | EDJ-KQ25720 | Human | 83464 | Details Get a Quote |
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