ATP2C1 Gene: Calcium-Transporting ATPase 2C1
Essential regulator of Golgi calcium homeostasis; mutations cause Hailey-Hailey disease
Gene Information Card
| Symbol | ATP2C1 |
|---|---|
| Full Name | ATPase secretory pathway Ca2+ transporting 1 |
| Gene Type | protein coding |
| Chromosomal Location | 3q22.1 |
| NCBI Gene ID | 27032 ncbi.nlm.nih.gov/gene/27032 |
| Ensembl ID | ENSG00000017260 |
| UniProt ID | P98194 |
| OMIM ID | 604384 |
| HGNC ID | 13211 |
| Aliases | SPCA1, ATP2C1A, ATP2C1B, BCPM |
Description
The ATP2C1 gene encodes the secretory pathway Ca2+/Mn2+ ATPase (SPCA1), a P-type ATPase localized to the Golgi apparatus. It transports cytosolic Ca2+ and Mn2+ into the Golgi lumen, essential for proper protein processing, glycosylation, and calcium signaling. Mutations in ATP2C1 cause Hailey-Hailey disease, an autosomal dominant skin disorder characterized by blisters and erosions in flexural areas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hailey-Hailey disease | Loss-of-function mutations in ATP2C1 reduce SPCA1 activity, impairing Golgi calcium uptake and leading to keratinocyte adhesion defects and acantholysis. | ClinVar, OMIM |
| Keratosis follicularis (Darier disease) - differential | Not directly caused by ATP2C1 mutations, but ATP2C1 dysfunction can mimic similar skin phenotypes. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.3 | Medium |
| Esophagus | 8.5 | Low |
| Kidney | 7.2 | Low |
| Liver | 5.1 | Low |
| Brain | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.2 | High expression; relevant to skin phenotype |
| HeLa | 10.1 | Moderate |
| HEK293 | 8.7 | Moderate |
| A549 | 6.3 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2021C>T (p.Thr674Met) | Missense | Rare | Reduced ATPase activity; associated with Hailey-Hailey disease |
| c.2545G>A (p.Gly849Ser) | Missense | Rare | Impaired calcium transport; pathogenic |
| c.IVS10+1G>A | Splice site | Rare | Aberrant splicing; loss of function |
| c.180delC (p.Leu60Trpfs*20) | Frameshift | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most ATP2C1 mutations are loss-of-function, leading to haploinsufficiency or dominant-negative effects, reducing SPCA1 activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type SPCA1 function.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • calcium ion transmembrane transporter activity |
| • manganese ion transmembrane transporter activity | • P-type calcium transporter activity |
| • Golgi membrane | • integral component of membrane |
| • calcium ion transport | • manganese ion transport |
| • Golgi organization |
Pathways
• Calcium signaling pathway
• Golgi-associated vesicle biogenesis
• Protein processing in endoplasmic reticulum
Protein Summary
SPCA1 is a 919-amino acid protein with 10 transmembrane domains, localized to the Golgi apparatus. It uses ATP to pump Ca2+ and Mn2+ into the Golgi lumen, crucial for protein glycosylation and sorting. It has two isoforms (SPCA1a and SPCA1b) with different C-termini. Mutations disrupt calcium homeostasis, leading to skin fragility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP2C1 Knockout HEK293 Cell Line | EDJ-KQ2711 | Human | 27032 | Details Get a Quote |
| ATP2C1 Knockout A-549 Cell Line | EDJ-KQ24943 | Human | 27032 | Details Get a Quote |
| ATP2C1 Knockout HCT 116 Cell Line | EDJ-KQ24945 | Human | 27032 | Details Get a Quote |
| ATP2C1 Knockout HeLa Cell Line | EDJ-KQ24946 | Human | 27032 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
