ANKH: Inorganic Pyrophosphate Transport Regulator
Key gene in calcium pyrophosphate deposition disease and craniometaphyseal dysplasia
Gene Information Card
| Symbol | ANKH |
|---|---|
| Full Name | ANKH inorganic pyrophosphate transport regulator |
| Gene Type | protein-coding |
| Chromosomal Location | 5p15.2 |
| NCBI Gene ID | 56172 ncbi.nlm.nih.gov/gene/56172 |
| Ensembl ID | ENSG00000154122 |
| UniProt ID | Q9HCJ1 |
| OMIM ID | 605145 |
| HGNC ID | 15492 |
| Aliases | ANK, ANK1, HANK, MGC26269 |
Description
The ANKH gene encodes a multipass transmembrane protein that regulates inorganic pyrophosphate (PPi) transport across the cell membrane. PPi is a critical inhibitor of hydroxyapatite and calcium pyrophosphate crystal formation. Mutations in ANKH are associated with calcium pyrophosphate deposition disease (CPPD) and craniometaphyseal dysplasia (CMD). The protein is expressed in various tissues, including cartilage, bone, and kidney.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Calcium Pyrophosphate Deposition Disease (CPPD) | Gain-of-function mutations increase PPi export, leading to extracellular PPi accumulation and calcium pyrophosphate crystal deposition in joints. | OMIM #118600 |
| Craniometaphyseal Dysplasia (CMD) | Loss-of-function mutations reduce PPi export, causing abnormal bone remodeling and craniofacial hyperostosis. | OMIM #123000 |
| Chondrocalcinosis 2 | Specific ANKH mutations (e.g., p.M48T) predispose to familial chondrocalcinosis. | OMIM #118600 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cartilage | 12.3 | Medium |
| Bone | 8.7 | Low |
| Kidney | 15.1 | Medium |
| Brain | 6.2 | Low |
| Liver | 4.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Chondrocytes | 14.5 | Primary cells |
| Osteoblasts | 10.2 | Primary cells |
| HEK293 | 8.9 | Embryonic kidney cells |
| HeLa | 5.3 | Cervical cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.M48T | Missense | Rare | Gain-of-function; associated with CPPD |
| p.C52R | Missense | Rare | Gain-of-function; associated with CPPD |
| p.E490K | Missense | Rare | Loss-of-function; associated with CMD |
| p.R524Q | Missense | Rare | Loss-of-function; associated with CMD |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.E490K and p.R524Q reduce PPi export, leading to craniometaphyseal dysplasia.
Gain of Function (GOF)
Mutations such as p.M48T and p.C52R increase PPi export, causing calcium pyrophosphate deposition disease.
Dominant Negative (DN)
Not reported for ANKH.
View complete mutation data：
Gene Ontology (GO)
| • GO:0015321 - sodium-dependent phosphate transmembrane transporter activity | • GO:0015293 - symporter activity |
| • GO:0005886 - plasma membrane | • GO:0016021 - integral component of membrane |
| • GO:0006817 - phosphate ion transport | • GO:0055074 - calcium ion homeostasis |
Pathways
• PPi metabolism and transport
• Regulation of bone mineralization
• Calcium pyrophosphate crystal formation
Protein Summary
The ANKH protein is a 492-amino-acid multipass transmembrane protein that functions as a pyrophosphate (PPi) transporter. It localizes to the plasma membrane and facilitates the efflux of intracellular PPi into the extracellular space. This process regulates mineralization by inhibiting hydroxyapatite and calcium pyrophosphate crystal formation. The protein is highly expressed in chondrocytes and osteoblasts, where it modulates cartilage and bone homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ANKH Knockout HEK293 Cell Line | EDJ-KQ2077 | Human | 56172 | Details Get a Quote |
| ANKH Knockout A-549 Cell Line | EDJ-KQ22159 | Human | 56172 | Details Get a Quote |
| ANKH Knockout HCT 116 Cell Line | EDC07825 | Human | 56172 | Details Get a Quote |
| ANKH Knockout HeLa Cell Line | EDJ-KQ22161 | Human | 56172 | Details Get a Quote |
| ANKHD1 Knockout HEK293 Cell Line | EDJ-KQ51395 | Human | 54882 | Details Get a Quote |
| ANKHD1-EIF4EBP3 Knockout HEK293 Cell Line | EDJ-KQ52331 | Human | 404734 | Details Get a Quote |
| ANKHD1 Knockout HeLa Cell Line | EDJ-KQ56494 | Human | 54882 | Details Get a Quote |
| ANKHD1-EIF4EBP3 Knockout HeLa Cell Line | EDJ-KQ60347 | Human | 404734 | Details Get a Quote |
| ANKHD1 Knockout A-549 Cell Line | EDJ-KQ64984 | Human | 54882 | Details Get a Quote |
| ANKHD1-EIF4EBP3 Knockout A-549 Cell Line | EDJ-KQ68814 | Human | 404734 | Details Get a Quote |
| ANKHD1 Knockout HCT 116 Cell Line | EDJ-KQ73430 | Human | 54882 | Details Get a Quote |
| ANKHD1-EIF4EBP3 Knockout HCT 116 Cell Line | EDJ-KQ77178 | Human | 404734 | Details Get a Quote |
Displaying Records 1 To 12 Of 12 Records
