Browse APH1A

Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Endoplasmic reticulum membrane Multi-pass membrane protein Golgi apparatus, Golgi stack membrane Multi-pass membrane protein Note=Predominantly located in the endoplasmic reticulum and in the cis-Golgi.
Domain PF06105 Aph-1 protein
Function

Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12297508, PubMed:12522139, PubMed:12763021, PubMed:12679784, PubMed:25043039, PubMed:26280335). Required for normal gamma-secretase assembly (PubMed:12522139, PubMed:12471034, PubMed:12763021, PubMed:19369254). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable).

> Gene Ontology
 
Biological Process GO:0001655 urogenital system development
GO:0001656 metanephros development
GO:0001822 kidney development
GO:0006509 membrane protein ectodomain proteolysis
GO:0007219 Notch signaling pathway
GO:0007220 Notch receptor processing
GO:0016485 protein processing
GO:0031293 membrane protein intracellular domain proteolysis
GO:0033619 membrane protein proteolysis
GO:0042982 amyloid precursor protein metabolic process
GO:0042987 amyloid precursor protein catabolic process
GO:0048013 ephrin receptor signaling pathway
GO:0051604 protein maturation
GO:0072001 renal system development
Molecular Function GO:0004175 endopeptidase activity
Cellular Component GO:0005795 Golgi stack
GO:0031984 organelle subcompartment
GO:0031985 Golgi cisterna
GO:0032580 Golgi cisterna membrane
GO:0070765 gamma-secretase complex
GO:0098791 Golgi subcompartment
> KEGG and Reactome Pathway
 
KEGG hsa04330 Notch signaling pathway
Reactome R-HSA-157212: A third proteolytic cleavage releases NICD
R-HSA-2122948: Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-422475: Axon guidance
R-HSA-204998: Cell death signalling via NRAGE, NRIF and NADE
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2682334: EPH-Ephrin signaling
R-HSA-3928665: EPH-ephrin mediated repulsion of cells
R-HSA-2979096: NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-205043: NRIF signals cell death from the nucleus
R-HSA-1251985: Nuclear signaling by ERBB4
R-HSA-193692: Regulated proteolysis of p75NTR
R-HSA-162582: Signal Transduction
R-HSA-1236394: Signaling by ERBB4
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer
R-HSA-1980145: Signaling by NOTCH2
R-HSA-1980148: Signaling by NOTCH3
R-HSA-1980150: Signaling by NOTCH4
R-HSA-166520: Signalling by NGF
R-HSA-193704: p75 NTR receptor-mediated signalling
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between APH1A and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.

Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of APH1A in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 0.71 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of APH1A in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0840.73
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.050.988
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.180.94
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.5050.198
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.5040.826
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5140.869
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0630.891
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.1850.929
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.2710.91
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2180.923
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.430.9
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2470.00304
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of APH1A in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of APH1A. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of APH1A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by APH1A.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of APH1A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of APH1A expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between APH1A and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolAPH1A
NameAPH1A gamma secretase subunit
Aliases APH-1A; CGI-78; anterior pharynx defective 1 homolog A (C. elegans); 6530402N02Rik; APH-1; anterior pharynx ......
Chromosomal Location1q21.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting APH1A collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting APH1A.
ID Name Drug Type Targets #Targets
DB05171E-2012Small MoleculeAPH1A, PSENEN2