ATP2A1

Chr 16AR

ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1

Also known as: ATP2A, SERCA1

NCBI Gene: 487ENSG00000196296UniProt: O14983

This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]

Primary Disease Associations & Inheritance

Brody myopathyMIM #601003
AR
UniProtBrody disease
100
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ATP2A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 25 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.50
OE 0.61 (0.46–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.54Z-score
OE missense 0.82 (0.76–0.89)
496 obs / 602.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.46–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.76–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 30 / 48.8Missense obs/exp: 496 / 602.3Syn Z: 0.04

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS25
Likely Benign62
12
Pathogenic
1
Likely Pathogenic
25
VUS
62
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
8
0
12
Likely Pathogenic
1
0
0
0
1
VUS
1
22
2
0
25
Likely Benign
0
0
25
37
62
Benign
0
0
0
0
0
Total6223537100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ATP2A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Brody myopathy

MIM #601003

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of potential drug targets for rheumatoid arthritis from genetic insights: a Mendelian randomization study.
Cao Y et al.·J Transl Med
2023
SERCA pumps and human diseases.
Hovnanian A·Subcell Biochem
2007Review
Disulfidptosis-related long non-coding RNA signature predicts the prognosis, tumor microenvironment, immunotherapy, and antitumor drug options in colon adenocarcinoma.
Wang K et al.·Apoptosis
2024
Identification of novel therapeutic targets for cognitive performance and associations with brain health.
Zhang LY et al.·Transl Psychiatry
2025
Altered SERCA Expression in Breast Cancer.
Christodoulou P et al.·Medicina (Kaunas)
2021
Identification of a pathogenic mutation in ATP2A1 via in silico analysis of exome data for cryptic aberrant splice sites.
Bruels CC et al.·Mol Genet Genomic Med
2019Case report
The Notch signaling pathway in skeletal muscle health and disease.
Vargas-Franco D et al.·Muscle Nerve
2022Review
Challenges in the diagnosis and treatment of the malignant adnexal neoplasms of the head and neck.
Wierzbicka M et al.·Curr Opin Otolaryngol Head Neck Surg
2023Review
Identification of endoplasmic reticulum stress-related genes associated with Alzheimer's disease risk: A multi-omics Mendelian randomization analysis.
Liang B et al.·J Affect Disord
2026
Clinical, morphological and genetic characterization of Brody disease: an international study of 40 patients.
Molenaar JP et al.·Brain
2020Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools