protein
Aspartyl/asparaginyl beta-hydroxylase
Gene
ASPH
Organism
Homo sapiens(9606)
Length
758 aa
Mass
85,863 Da
Aspartyl/asparaginyl beta-hydroxylase (ASPH) is a calcium-sensing protein that catalyzes hydroxylation of aspartate or asparagine residues within epidermal growth factor-like domains of various substrates (UniProt: Q12797). The enzyme functions as a structural component of endoplasmic reticulum–plasma membrane junctions and modulates calcium-release-activated calcium channel activity in immune cells. ASPH is a 758-amino-acid membrane-bound protein expressed in human tissues.
UniProt documents a monogenic association with facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebs (FDLAB; MIM 601552), highlighting the protein's importance in connective tissue and ocular development. The molecular function in EGF-domain modification suggests roles in cell signaling and structural protein maturation across multiple tissues.
In Alzheimer's disease, ASPH is upregulated in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics: mean log₂FC = 0.45, detected across 2 of 4 subcellular fractions in TMT-labeled quantitative proteomics). This modest elevation may reflect altered calcium homeostasis or ER stress responses characteristic of the AD pathological state, though functional implications remain to be determined.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
+0.428
S2
not detected
S3
+0.479
Mean log₂FC across detected fractions: +0.4534 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins
Membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells
Disease associations
Facial dysmorphism, lens dislocation, anterior segment abnormalities, and spontaneous filtering blebsFDLAB
A syndrome characterized by dislocated crystalline lenses and anterior segment abnormalities in association with a distinctive facies involving flat cheeks and a beaked nose. Some affected individuals develop highly unusual non-traumatic conjunctival cysts (filtering blebs).
Sources
Last updated 5/8/2026, 6:29:12 AM