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APH1B aph-1 homolog B, gamma-secretase subunit [ Homo sapiens (human) ]

Gene ID: 83464, updated on 2-Nov-2024

Summary

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Official Symbol
APH1Bprovided by HGNC
Official Full Name
aph-1 homolog B, gamma-secretase subunitprovided by HGNC
Primary source
HGNC:HGNC:24080
See related
Ensembl:ENSG00000138613 MIM:607630; AllianceGenome:HGNC:24080
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PSFL; APH-1B; PRO1328; TAAV688; aph-1beta
Summary
This gene encodes a multi-pass transmembrane protein that is a functional component of the gamma-secretase complex, which also contains presenilin and nicastrin. This protein represents a stabilizing cofactor for the presenilin holoprotein in the complex. The gamma-secretase complex catalyzes the cleavage of integral proteins such as notch receptors and beta-amyloid precursor protein. [provided by RefSeq, Sep 2011]
Expression
Broad expression in testis (RPKM 23.1), thyroid (RPKM 13.1) and 22 other tissues See more
Orthologs
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Genomic context

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See APH1B in Genome Data Viewer
Location:
15q22.2
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (63277605..63309126)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (61082385..61113909)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (63569804..63601325)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6512 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9528 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63485907-63486407 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr15:63502826-63503391 Neighboring gene RAB8B, member RAS oncogene family Neighboring gene uncharacterized LOC124903504 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6513 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6514 Neighboring gene uncharacterized LOC124903506 Neighboring gene uncharacterized LOC124903505 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63630428-63631324 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:63637609-63637796 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_40513 Neighboring gene carbonic anhydrase 12 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63673729-63674249 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:63674250-63674769 Neighboring gene long intergenic non-protein coding RNA 2568

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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

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Related articles in PubMed

  1. Identification and characterization of a novel human APH-1b splice variant lacking exon 4. Saito S, et al. Biochem Biophys Res Commun, 2005 May 20. PMID 15823552
  2. Negative evidence for a role of APH1B T27I variant in Alzheimer's disease. Zhang X, et al. Hum Mol Genet, 2020 Apr 15. PMID 31995180
  3. Correlation between HIV-1 seropositivity and prevalence of a gamma-secretase polymorphism in two distinct ethnic populations. van Loo KM, et al. J Med Virol, 2009 Nov. PMID 19774691
  4. Identification of distinct gamma-secretase complexes with different APH-1 variants. Shirotani K, et al. J Biol Chem, 2004 Oct 1. PMID 15286082
  5. Characterization of APH-1 mutants with a disrupted transmembrane GxxxG motif. Araki W, et al. J Mol Neurosci, 2006. PMID 16757808

See all (40) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-beta deposition in Alzheimer's disease.
    Title: Dysregulated expression levels of APH1B in peripheral blood are associated with brain atrophy and amyloid-β deposition in Alzheimer's disease.
  2. Negative evidence for a role of APH1B T27I variant in Alzheimer's disease.
    Title: Negative evidence for a role of APH1B T27I variant in Alzheimer's disease.
  3. Data show that presenilin 1 (PS1)/anterior-pharynx-defective protein 1 (Aph1b), presenilin 2 (PS2)/Aph1aL, PS2/Aph1aS and PS2/anterior pharynx defective 1 homolog B (Aph1b) gamma-secretase produced amyloid beta peptide (Abeta) with a higher Abeta42+Abeta43-to-Abeta40 (Abeta42(43)/Abeta40) ratio than the other gamma-secretases.
    Title: Specific combinations of presenilins and Aph1s affect the substrate specificity and activity of γ-secretase.
  4. gamma-Secretase inhibition during repeated peripheral inflammation blocks central amyloid-beta accumulation and prevents cognitive dysfunction.
    Title: Imatinib methanesulfonate reduces hippocampal amyloid-β and restores cognitive function following repeated endotoxin exposure.
  5. The single-nucleotide polymorphism (Phe217Leu; rs1047552) showed a tendency for association with HIV-1 infection in a Xhosa indigenous South African Bantu study (P = 0.087), and associated significantly in a Caucasian Dutch study (P = 0.049).
    Title: Correlation between HIV-1 seropositivity and prevalence of a gamma-secretase polymorphism in two distinct ethnic populations.
  6. A non-synonymous SNP in the gamma-secretase component APH1B (Phe217Leu; rs1047552)is significantly associated with premature coronary atherosclerosis in Dutch males.
    Title: Male-specific association between a gamma-secretase polymorphism and premature coronary atherosclerosis.
  7. These data suggest that a cooperative mechanism involving APOE and APH-1b plays a role in the susceptibility to develop AD.
    Title: Interaction between the APOE epsilon4 allele and the APH-1b c + 651T > G SNP in Alzheimer's disease.
  8. Observational study of gene-disease association. (HuGE Navigator)
    Title: Correlation between HIV-1 seropositivity and prevalence of a gamma-secretase polymorphism in two distinct ethnic populations.
  9. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
    Title: Interaction between the APOE epsilon4 allele and the APH-1b c + 651T > G SNP in Alzheimer's disease.
  10. knock down of APH-1a, but not APH-1b, resulted in impaired maturation of nicastrin and reduced expression of presenilin 1, presenilin 2, and PEN-2 proteins
    Title: Expression profiles of two human APH-1 genes and their roles in formation of presenilin complexes.
Submit: New GeneRIF Correction See all GeneRIFs (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ33115, DKFZp564D0372

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 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 NAS
Non-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 ISS
Inferred from Sequence or Structural Similarity
more info
  
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 membrane protein intracellular domain proteolysis ISS
Inferred from Sequence or Structural Similarity
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
  
acts_upstream_of_or_within protein processing IDA
Inferred from Direct Assay
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 
Component Evidence Code Pubs
located_in Golgi membrane NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
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 IGI
Inferred from Genetic Interaction
more info
 PubMed 
part_of gamma-secretase complex ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in 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 transport vesicle IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
gamma-secretase subunit APH-1B
Names
APH1B gamma secretase subunit
anterior pharynx defective 1 homolog B

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.

mRNA and Protein(s)

  1. NM_001145646.2 → NP_001139118.1  gamma-secretase subunit APH-1B isoform 2

    See identical proteins and their annotated locations for NP_001139118.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an in-frame coding exon and encodes a shorter isoform (2), as compared to variant 1.
    Source sequence(s)
    AB189172, AC016207, AI693802, DA397427
    Consensus CDS
    CCDS45276.1
    UniProtKB/Swiss-Prot
    Q8WW43
    Related
    ENSP00000369700.4, ENST00000380343.8
    Conserved Domains (1) summary
    pfam06105
    Location:3 → 191
    Aph-1; Aph-1 protein

  2. NM_031301.4 → NP_112591.2  gamma-secretase subunit APH-1B isoform 1

    See identical proteins and their annotated locations for NP_112591.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AC016207, AI693802, AK291204, DA397427
    Consensus CDS
    CCDS10184.1
    UniProtKB/Swiss-Prot
    A8K589, Q564N3, Q6UWQ1, Q8WW43, Q9H0S0
    Related
    ENSP00000261879.5, ENST00000261879.10
    Conserved Domains (1) summary
    pfam06105
    Location:3 → 232
    Aph-1; Aph-1 protein

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_000015.10 Reference GRCh38.p14 Primary Assembly

    Range
    63277605..63309126
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011522105.4 → XP_011520407.1  gamma-secretase subunit APH-1B isoform X1

    Conserved Domains (1) summary
    pfam06105
    Location:2 → 187
    Aph-1; Aph-1 protein

  2. XM_024450085.2 → XP_024305853.1  gamma-secretase subunit APH-1B isoform X2

    UniProtKB/TrEMBL
    H0YKZ9
    Related
    ENSP00000453002.1, ENST00000560890.5
    Conserved Domains (1) summary
    pfam06105
    Location:18 → 178
    Aph-1; Aph-1 protein

RNA

  1. XR_007064490.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060939.1 Alternate T2T-CHM13v2.0

    Range
    61082385..61113909
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054378982.1 → XP_054234957.1  gamma-secretase subunit APH-1B isoform X1

  2. XM_054378983.1 → XP_054234958.1  gamma-secretase subunit APH-1B isoform X2

RNA

  1. XR_008489018.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8WW43.3 GenPept UniProtKB/Swiss-Prot:Q8WW43

Gene LinkOut

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