ANKH
Function
Transports adenosine triphosphate (ATP) and possibly other nucleoside triphosphates (NTPs) from cytosol to the extracellular space. Mainly regulates their levels locally in peripheral tissues while playing a minor systemic role. Prevents abnormal ectopic mineralization of the joints by regulating the extracellular levels of the calcification inhibitor inorganic pyrophosphate (PPi), which originates from the conversion of extracellular NTPs to NMPs and PPis by ENPP1 (PubMed:20943778, PubMed:32639996, PubMed:35147247). Regulates the release of the TCA cycle intermediates to the extracellular space, in particular citrate, succinate and malate. Extracellular citrate mostly present in bone tissue is required for osteogenic differentiation of mesenchymal stem cells, stabilization of hydroxyapatite structure and overall bone strength (PubMed:32639996). The transport mechanism remains to be elucidated (Probable).
Involvement in disease
Chondrocalcinosis 2
CCAL2
Chondrocalcinosis is a common cause of joint pain and arthritis caused by calcium deposition in articular cartilage and the presence of calcium hypophosphate crystals in synovial fluid, cartilage and periarticular soft tissue. CCAL2 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Craniometaphyseal dysplasia, autosomal dominant
CMDD
An osteochondrodysplasia characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that may finally result in hearing loss and facial palsy.
None
The disease is caused by variants affecting the gene represented in this entry.
A missense variant of ANKH cosegregates with a complex phenotype according to an autosomal recessive pattern. Affected homozygous individuals from a large consanguinous family show sensorineural and conductive hearing loss, intellectual disability, spinal ankylosis, and periarticular calcification of small joints. Only a mild arthropathy is observed in heterozygous individuals.
Sequence Similarities
Belongs to the ANKH family.
Tissue Specificity
Found in osteoblasts from mandibular bone and from iliac bone; not detected in osteoclastic cells.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
KIAA1581, UNQ241/PRO274, ANKH, Mineralization regulator ANKH, ATP carrier protein ANKH, Progressive ankylosis protein homolog, ANK