Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

ALDH4A1 is the mitochondrial matrix NAD+-dependent delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDH; EC 1.2.1.88). It oxidizes L-glutamate gamma-semialdehyde, the open-chain form in equilibrium with pyrroline-5-carboxylate, to L-glutamate, producing NADH. This is the second and final catalytic step of proline degradation; the same semialdehyde can also arise from ornithine. ALDH4A1 also acts in trans-4-hydroxy-L-proline catabolism by oxidizing the corresponding hydroxylated semialdehyde. Human P5CDH forms a domain-swapped homodimer, with NAD+-binding and catalytic domains and the catalytic cysteine Cys348. Biallelic loss-of-function variants cause type II hyperprolinemia, with proline and pyrroline-5-carboxylate accumulation. A separate noncatalytic activity has been demonstrated in human-cell and purified-protein experiments: ALDH4A1 associates with MPC1-MPC2 and increases reconstituted mitochondrial pyruvate-carrier transport, including with the catalytically inactive S352L variant. MPC1-MPC2 themselves form the translocation pathway and transport without added ALDH4A1; ALDH4A1 is therefore supported as an accessory transport-enhancing factor, while its native occupancy, stoichiometry and contribution across tissues remain unresolved.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.