ATP2C1

Chr 3AD

ATPase secretory pathway Ca2+ transporting 1

Also known as: ATP2C1A, BCPM, HHD, PMR1, SPCA1, hSPCA1

NCBI Gene: 27032 ENSG00000017260 UniProt: P98194 OMIM: 604384

The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium ions. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hailey-Hailey diseaseMIM #169600

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hailey-Hailey disease; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.18LOEUF

pLI 1.000

Z-score 6.43

OE 0.09 (0.04–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.67Z-score

OE missense 0.54 (0.49–0.60)

280 obs / 514.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.18)

0≤0.351.4

Missense OE?0.54 (0.49–0.60)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 5 / 57.7Missense obs/exp: 280 / 514.5Syn Z: 0.32

Background carrier burden — how many people carry a rare variant somewhere in ATP2C1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

870 rare PASS variants

Rare truncating (LoF)

1 in 1,400

101 rare PASS variants

Rare synonymous (reference)

1 in 150

402 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ATP2C1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 1,300
South Asian	~43k	1 in 100	1 in 1,500
Remaining (unassigned)	~30k	1 in 82	1 in 2,100
European (Finnish)	~27k	1 in 390	1 in 2,400
Admixed American	~22k	1 in 100	1 in 3,300
African / African American	~21k	1 in 100	1 in 1,900
East Asian	~20k	1 in 97	1 in 3,300
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 160	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 24 of 27 coding exons well covered in gnomAD exomes; exons 4, 11, 12 marginal. Genomes: all 27.? see exons ↓