ATP2A2

Highest pathogenic variant AF is 0.000006571857

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000539276

Coding exons

20

Length

70338

Individuals with no LoFs

125741

Homozygous LoFs

0

Heterozygous LoFs

7

Defined

125748

p

0.0000278

Function

FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform 2 is involved in the regulation of the contraction/relaxation cycle (PubMed:16402920). Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11- induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation (By similarity). {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:16402920}.;

Disease

DISEASE: Acrokeratosis verruciformis (AKV) [MIM:101900]: A localized disorder of keratinization, which is inherited as an autosomal dominant trait. Its onset is early in life with multiple flat-topped, flesh-colored papules on the hands and feet, punctate keratoses on the palms and soles, with varying degrees of nail involvement. The histopathology shows a distinctive pattern of epidermal features with hyperkeratosis, hypergranulosis and acanthosis together with papillomatosis. These changes are frequently associated with circumscribed elevations of the epidermis that are said to resemble church spires. There are no features of dyskeratosis or acantholysis, the typical findings in lesions of Darier disease. {ECO:0000269|PubMed:12542527}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Darier disease (DD) [MIM:124200]: A skin disorder characterized by warty papules and plaques in seborrheic areas (central trunk, flexures, scalp and forehead), palmoplantar pits and distinctive nail abnormalities. It is due to loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Patients with mild disease may have no more than a few scattered keratotic papules or subtle nail changes, whereas those with severe disease are handicapped by widespread malodorous keratotic plaques. Some patients present with hemorrhage into acantholytic vesicles on the palms and dorsal aspects of the fingers which gives rise to black macules. In a few families affected by Darier disease, neuropsychiatric abnormalities such as mild mental retardation, schizophrenia, bipolar disorder and epilepsy have been reported. Stress, UV exposure, heat, sweat, friction and oral contraception exacerbate disease symptoms. Clinical variants of Darier disease include hypertrophic, vesicobullous, hypopigmented, cornifying, zosteriform or linear, acute and comedonal subtypes. Comedonal Darier disease is characterized by the coexistence of acne-like comedonal lesions with typical Darier hyperkeratotic papules on light-exposed areas. At histopathologic level, comedonal Darier disease differs from classic Darier disease in the prominent follicular involvement and the presence of greatly elongated dermal villi. {ECO:0000269|PubMed:10080178, ECO:0000269|PubMed:10441323, ECO:0000269|PubMed:10441324, ECO:0000269|PubMed:10441325, ECO:0000269|PubMed:19995371, ECO:0000269|PubMed:28035777}. Note=The disease is caused by mutations affecting the gene represented in this entry.;