ALDH2

Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.

AMED syndrome, digenic

AMEDS

A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. AMEDS is an autosomal recessive, digenic form characterized by childhood onset of bone marrow failure resulting in aplastic anemia, in association with global developmental delay, intellectual disability, and poor overall growth with short stature.

None

The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. AMEDS patients carry ADH5 biallelic variants and homozygous or heterozygous ALDH2 variant p.Glu504Lys, affecting protein activity. Cellular and animal studies demonstrate that the simultaneous loss of ALDH2 and ADH5 activities leads to an increase of cellular formaldehyde sensitivity and multisystem abnormalities including hematopoietic failure.

Alcohol metabolism; ethanol degradation; acetate from ethanol: step 2/2.

In response to mitochondrial stress, the precursor protein is ubiquitinated by the SIFI complex in the cytoplasm before mitochondrial import, leading to its degradation (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121).

Belongs to the aldehyde dehydrogenase family.

• Mitochondrion matrix

ALDM, ALDH2, ALDH class 2, ALDH-E2, ALDHI

• entrezGene:217
• omim:100650
• swissprot:P05091

Proteins

Metabolism

56381Da