protein
Alpha-aminoadipic semialdehyde synthase, mitochondrial
Gene
AASS
Organism
Homo sapiens(9606)
Length
926 aa
Mass
102,132 Da
Alpha-aminoadipic semialdehyde synthase (AASS) is a mitochondrial bifunctional enzyme that catalyzes the first two steps in lysine degradation (UniProt: Q9UDR5). The protein functions in amino acid metabolism within mitochondria, a critical compartment for cellular energy production and metabolic homeostasis. Loss-of-function mutations in AASS cause hyperlysinemia and related inborn errors of metabolism affecting lysine and fatty acid processing, which can result in encephalopathy and neurologic abnormalities in severe cases (UniProt: Q9UDR5).
In Alzheimer's Disease, AASS is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is +0.7026 across three subcellular fractions in a TMT-labeled quantitative proteomics study of four subcellular compartments. This elevation may reflect compensatory changes in mitochondrial lysine catabolism or energy metabolism in response to AD-related neurodegeneration. The functional significance of increased AASS expression in AD pathogenesis remains 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
+0.598
S2
+0.917
S3
+0.593
Mean log₂FC across detected fractions: +0.7026 (3 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
Bifunctional enzyme that catalyzes the first two steps in lysine degradation
Disease associations
Hyperlysinemia, 1HYPLYS1
An autosomal recessive metabolic condition with variable clinical features. Some patients present with non-specific seizures, hypotonia, or mildly delayed psychomotor development, and increased serum lysine and pipecolic acid on laboratory analysis. However, about half of the probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant.
2,4-dienoyl-CoA reductase deficiencyDECRD
A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia.
Sources
Last updated 5/8/2026, 6:39:41 AM