protein
Methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase [acylating], mitochondrial
aka MMSDH
Gene
ALDH6A1
Organism
Homo sapiens(9606)
Length
535 aa
Mass
57,840 Da
ALDH6A1 encodes methylmalonate-semialdehyde/malonate-semialdehyde dehydrogenase (MMSDH), a mitochondrial enzyme that catalyzes the dehydrogenation of malonate and methylmalonate semialdehydes (UniProt: Q02252). This enzyme functions in the catabolism of valine, thymine, and beta-alanine-derived compounds, including uracil and cytidine, playing a role in amino acid and nucleotide base metabolism.
Mutations in ALDH6A1 cause methylmalonate semialdehyde dehydrogenase deficiency (MMSDHD, MIM 614105), a metabolic disorder marked by accumulation of beta-alanine and related organic acids in urine (UniProt: Q02252). The protein's mitochondrial localization reflects its involvement in metabolic homeostasis.
ALDH6A1 is associated with Alzheimer's Disease according to Chaparral curation. In post-mortem AD brain tissue, the protein is upregulated relative to age-matched controls, with a mean log2 fold-change of 0.62 across analyzed subcellular fractions (Chaparral AD proteomics). This elevation suggests altered metabolic enzyme abundance in AD pathology, though the functional consequences 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
+0.615
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: +0.6154 (1 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
Malonate and methylmalonate semialdehyde dehydrogenase involved in the catabolism of valine, thymine, and compounds catabolized by way of beta-alanine, including uracil and cytidine
Disease associations
Methylmalonate semialdehyde dehydrogenase deficiencyMMSDHD
A metabolic disorder characterized by elevated beta-alanine, 3-hydroxypropionic acid, and both isomers of 3-amino and 3-hydroxyisobutyric acids in urine organic acids.
Sources
Last updated 5/8/2026, 6:34:23 AM