Seroatlas · Human Serome Atlas

APH1A

Gamma-secretase subunit APH-1A

Also known as: APH-1A, APH1A_HUMAN, CGI-78

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q96BI3
Gene: APH1A
Ensembl: ENSG00000117362
Chromosome: 1
Canonical length: 265 aa
Protein class: Predicted membrane proteins, Transporters
Quaternary structure: Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

265 residues, UniProt reviewed canonical sequence.

>Q96BI3|APH1A
     1  MGAAVFFGCT FVAFGPAFAL FLITVAGDPL RVIILVAGAF FWLVSLLLAS VVWFILVHVT
    61  DRSDARLQYG LLIFGAAVSV LLQEVFRFAY YKLLKKADEG LASLSEDGRS PISIRQMAYV
   121  SGLSFGIISG VFSVINILAD ALGPGVVGIH GDSPYYFLTS AFLTAAIILL HTFWGVVFFD
   181  ACERRRYWAL GLVVGSHLLT SGLTFLNPWY EASLLPIYAV TVSMGLWAFI TAGGSLRSIQ
   241  RSLLCRRQED SRVMVYSALR IPPED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against APH1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Other membrane
Secreted: No
Transmembrane segments: 7
Mean surface accessibility (rSASA): 0.32
Highest tissue expression: 128 nTPM

Expression across tissuesHPA

Tissue

liver: 128 nTPM
skin: 114 nTPM
esophagus: 114 nTPM
parathyroid gland: 104 nTPM
ovary: 98 nTPM
spleen: 94 nTPM

Single-cell type

esophageal apical cells: 374 nCPM
syncytiotrophoblasts: 194 nCPM
esophageal suprabasal cells: 191 nCPM
hofbauer cells: 188 nCPM
extravillous trophoblasts: 181 nCPM
migrating cytotrophoblasts: 161 nCPM

Immune cell

NK-cell: 12 nTPM
MAIT T-cell: 12 nTPM
gdT-cell: 11 nTPM
classical monocyte: 11 nTPM
non-classical monocyte: 11 nTPM
myeloid DC: 9.9 nTPM

Brain region

medulla oblongata: 63 nTPM
spinal cord: 60 nTPM
thalamus: 58 nTPM
basal ganglia: 53 nTPM
white matter: 53 nTPM
midbrain: 51 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.45
gnomAD pLI: 0.79
gnomAD missense Z: 2.03
DepMap mean gene effect: -0.28
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 15% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of APH1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads APH1A as an antibody target. Whether an autoantibody or antibody against APH1A could matter depends on whether native APH1A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

APH1A is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label APH1A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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