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

Summary

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: mouse all
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Genomic context

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_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A007E02 (e-PCR)
- UniSTS:15620

D15S734E (e-PCR)
- UniSTS:151628

WI-10749 (e-PCR)
- UniSTS:76917

STS-N31710 (e-PCR)
- UniSTS:66955

RH119833 (e-PCR)
- UniSTS:133578

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)

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
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

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

63277605..63309126

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

XR_007064490.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

61082385..61113909

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054378982.1 → XP_054234957.1 gamma-secretase subunit APH-1B isoform X1
XM_054378983.1 → XP_054234958.1 gamma-secretase subunit APH-1B isoform X2

UniProtKB/TrEMBL

H0YKZ9