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APH1A aph-1 homolog A, gamma-secretase subunit [ Homo sapiens (human) ]

Gene ID: 51107, updated on 25-Nov-2021

Summary

Official Symbol
APH1Aprovided by HGNC
Official Full Name
aph-1 homolog A, gamma-secretase subunitprovided by HGNC
Primary source
HGNC:HGNC:29509
See related
Ensembl:ENSG00000117362 MIM:607629
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
APH-1; APH-1A; CGI-78; 6530402N02Rik
Summary
This gene encodes a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1 homolog B (APH1B), along with the presenilin, nicastrin, and presenilin enhancer-2 proteins. The precise function of this seven-transmembrane-domain protein is unknown though it is suspected of facilitating the association of nicastrin and presenilin in the gamma secretase complex as well as interacting with substrates of the gamma secretase complex prior to their proteolytic processing. Polymorphisms in a promoter region of this gene have been associated with an increased risk for developing sporadic Alzheimer's disease. Alternative splicing results in multiple protein-coding and non-protein-coding transcript variants. [provided by RefSeq, Aug 2011]
Expression
Ubiquitous expression in thyroid (RPKM 47.4), colon (RPKM 37.4) and 25 other tissues See more
Orthologs
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Genomic context

See APH1A in Genome Data Viewer
Location:
1q21.2
Exon count:
8
Annotation release Status Assembly Chr Location
109.20211119 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (150265404..150282179, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (150237804..150241416, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene RNA, U2 small nuclear 17, pseudogene Neighboring gene carbonic anhydrase 14 Neighboring gene small nucleolar RNA, C/D box 13C Neighboring gene chromosome 1 open reading frame 54 Neighboring gene Sharpr-MPRA regulatory region 3157 Neighboring gene circadian associated repressor of transcription Neighboring gene uncharacterized LOC105371434

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Biological insights from 108 schizophrenia-associated genetic loci.
GeneReviews: Not available

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables endopeptidase activator activity IGI
Inferred from Genetic Interaction
more info
PubMed 
enables endopeptidase activator activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables enzyme binding IEA
Inferred from Electronic Annotation
more info
 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein-macromolecule adaptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables protein-macromolecule adaptor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
Process Evidence Code Pubs
involved_in Notch receptor processing IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in Notch receptor processing IDA
Inferred from Direct Assay
more info
PubMed 
involved_in Notch receptor processing IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in Notch receptor processing TAS
Traceable Author Statement
more info
PubMed 
involved_in Notch signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in amyloid precursor protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in amyloid precursor protein catabolic process IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in amyloid precursor protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in amyloid precursor protein catabolic process TAS
Traceable Author Statement
more info
PubMed 
involved_in amyloid precursor protein metabolic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in amyloid-beta formation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in amyloid-beta formation IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in amyloid-beta formation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in membrane protein ectodomain proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in membrane protein intracellular domain proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in membrane protein intracellular domain proteolysis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in metanephros development IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of catalytic activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of endopeptidase activity IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in positive regulation of endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in protein processing IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in protein processing IDA
Inferred from Direct Assay
more info
PubMed 
involved_in protein processing IGI
Inferred from Genetic Interaction
more info
PubMed 
involved_in protein processing IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
located_in Golgi cisterna membrane IEA
Inferred from Electronic Annotation
more info
 
located_in early endosome IEA
Inferred from Electronic Annotation
more info
 
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
PubMed 
located_in endosome membrane TAS
Traceable Author Statement
more info
 
part_of gamma-secretase complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
part_of gamma-secretase complex IDA
Inferred from Direct Assay
more info
PubMed 
part_of gamma-secretase complex IPI
Inferred from Physical Interaction
more info
PubMed 
is_active_in integral component of membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in integral component of membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in integral component of presynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
located_in membrane HDA PubMed 
located_in mitochondrion IEA
Inferred from Electronic Annotation
more info
 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
 
located_in synaptic vesicle IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
gamma-secretase subunit APH-1A
Names
APH1A gamma secretase subunit
anterior pharynx defective 1 homolog A
aph-1alpha
presenilin-stabilization factor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029952.1 RefSeqGene

    Range
    5194..8806
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001077628.3NP_001071096.1  gamma-secretase subunit APH-1A isoform 1

    See identical proteins and their annotated locations for NP_001071096.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1; also known as isoform L).
    Source sequence(s)
    BC020590, BI760743, DC365601
    Consensus CDS
    CCDS41390.1
    UniProtKB/Swiss-Prot
    Q96BI3
    Related
    ENSP00000358105.3, ENST00000369109.8
    Conserved Domains (1) summary
    pfam06105
    Location:3233
    Aph-1; Aph-1 protein
  2. NM_001243771.2NP_001230700.1  gamma-secretase subunit APH-1A isoform 3

    See identical proteins and their annotated locations for NP_001230700.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks a 5' exon and contains an alternate segement at the 3'end that results in a frameshift and premature stop codon, compared to variant 1. This variant encodes an isoform (3) with a shorter N-terminus and a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AK300640, BC017699, BI760743, DC365601
    UniProtKB/Swiss-Prot
    Q96BI3
    UniProtKB/TrEMBL
    B4DUG7
    Conserved Domains (1) summary
    pfam06105
    Location:3176
    Aph-1; Aph-1 protein
  3. NM_001243772.2NP_001230701.1  gamma-secretase subunit APH-1A isoform 4

    See identical proteins and their annotated locations for NP_001230701.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks a 5' exon and lacks a segment of a 5' exon, compared to variant 1. This variant encodes an isoform (4) with a shorter and distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    AK298832, BC017699, BI760743
    Consensus CDS
    CCDS58025.1
    UniProtKB/Swiss-Prot
    Q96BI3
    Related
    ENSP00000397473.2, ENST00000414276.6
    Conserved Domains (1) summary
    pfam06105
    Location:3163
    Aph-1; Aph-1 protein
  4. NM_016022.4NP_057106.2  gamma-secretase subunit APH-1A isoform 2

    See identical proteins and their annotated locations for NP_057106.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate segement in the 3' terminus that results in a frameshift and premature stop codon, compared to variant 1, and encodes an isoform (2; also known as isoform S) with a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    BC009501, BI760743, DC365601
    Consensus CDS
    CCDS41391.1
    UniProtKB/Swiss-Prot
    Q96BI3
    Related
    ENSP00000353380.4, ENST00000360244.8
    Conserved Domains (1) summary
    pfam06105
    Location:3233
    Aph-1; Aph-1 protein

RNA

  1. NR_045033.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an alternate segment of a 5' exon, compared to variant 1, which results in a frameshift and early stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated and the transcript is a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK297680, BC008732, BI760743, DC365601
  2. NR_045034.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks multiple 5' exons, compared to variant 1, which results in a frameshift and early stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated and the transcript is a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK307358, BC017699, BI760743
  3. NR_045035.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks a 5' exon, compared to variant 1, which results in a frameshift and early stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated and the transcript is a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK298876, BC017699, BI760743, DC365601

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20211119

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    150265404..150282179 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017001417.2XP_016856906.1  gamma-secretase subunit APH-1A isoform X2

    Conserved Domains (1) summary
    pfam06105
    Location:3176
    Aph-1; Aph-1 protein
  2. XM_024447455.1XP_024303223.1  gamma-secretase subunit APH-1A isoform X1

    Conserved Domains (1) summary
    pfam06105
    Location:3284
    Aph-1; Aph-1 protein
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