DNAJC12 Human

DnaJ (Hsp40) Homolog, Subfamily C, Member 12, also known as DNAJC12, is a member of the DnaJ/Hsp40 family of proteins. These proteins are molecular chaperones that play a crucial role in protein folding, assembly, and translocation. DNAJC12 is particularly significant due to its involvement in various cellular processes and its association with certain genetic disorders.

DNAJC12 belongs to a subclass of the DnaJ/Hsp40 family characterized by the presence of a J domain and a highly conserved C-terminal domain. Unlike other members of the family, DNAJC12 lacks the glycine/phenylalanine-rich (G/F) domain and the central repeat region (CRR). The J domain is essential for its interaction with Hsp70 proteins, which are critical for protein folding and stress responses .

The DNAJC12 gene is located on chromosome 10q21.3 and consists of five exons . The gene produces two isoforms through alternative polyadenylation sites. The primary isoform encodes a 198-amino acid protein, while the shorter isoform encodes a 107-amino acid protein . Expression of DNAJC12 is highest in the brain, heart, and testis, with lower levels observed in the kidney and stomach .

DNAJC12 interacts with several key proteins, including HSC70 (HSPA8), tyrosine hydroxylase (TH), peripheral tryptophan hydroxylase (TPH1), neuronal TPH2, and phenylalanine hydroxylase (PAH) . These interactions suggest that DNAJC12 plays a role in the regulation of these enzymes, which are involved in neurotransmitter synthesis and metabolic processes.

Mutations in the DNAJC12 gene have been linked to mild non-BH4-deficient hyperphenylalaninemia, a metabolic disorder characterized by elevated levels of phenylalanine in the blood . This condition can lead to neurological symptoms if left untreated. Understanding the function and regulation of DNAJC12 is crucial for developing therapeutic strategies for related disorders.