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

    Gene ID: 51107, updated on 9-Dec-2024

    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; AllianceGenome:HGNC:29509
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See APH1A in Genome Data Viewer
    Location:
    1q21.2
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (150265404..150269016, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (149390321..149393933, complement)
    RS_2024_09 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 NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:150208844-150209411 Neighboring gene RNA, U2 small nuclear 17, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:150228359-150229053 Neighboring gene carbonic anhydrase 14 Neighboring gene small nucleolar RNA, C/D box 13C Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:150241516-150242127 Neighboring gene uncharacterized LOC124904414 Neighboring gene chromosome 1 open reading frame 54 Neighboring gene Sharpr-MPRA regulatory region 3157 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1679 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:150254031-150255230 Neighboring gene circadian associated repressor of transcription

    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?

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    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
     
    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
     
    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 NAS
    Non-traceable Author Statement
    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
     
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    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 membrane protein intracellular domain proteolysis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in metanephros development IEA
    Inferred from Electronic Annotation
    more info
     
    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
     
    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 Golgi membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    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
     
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in endoplasmic reticulum membrane NAS
    Non-traceable Author Statement
    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
     
    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 
    part_of gamma-secretase complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in membrane HDA PubMed 
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in presynaptic membrane IEA
    Inferred from Electronic Annotation
    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)

    NEW Try the new Transcript table

    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_029952.2 RefSeqGene

      Range
      5000..8612
      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
      B4DQK0, Q5TB22, Q5TB23, Q969R6, Q96BI3, Q9BVG0, Q9Y386
      UniProtKB/TrEMBL
      B3KQT0
      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/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/TrEMBL
      B3KQT0
      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: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      150265404..150269016 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047422066.1XP_047278022.1  gamma-secretase subunit APH-1A isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      149390321..149393933 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054336892.1XP_054192867.1  gamma-secretase subunit APH-1A isoform X1