ATP2C1

protein-coding

ATPase secretory pathway Ca2+ transporting 1, the group of ATPases Ca2+ transporting

Gene summary

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]

Previous symbols:

BCPM

MANE transcript

NM_001378687.1

Inheritance

ClinVar variants

P:68U:133B:29

Top phenotype

Hailey-Hailey disease

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr3:130,850,595-131,016,712

External References & Databases

Ensembl (ENSG00000017260)

Transcript & Mutation Effects

hg38 • Region Span ~166.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Hailey-Hailey diseaseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008218

Submitter: Labcorp Genetics (formerly Invitae)

Hailey-Hailey diseaseDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008218

Submitter: G2P

Hailey-Hailey diseaseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008218

Submitter: PanelApp Australia

Hailey-Hailey diseaseSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008218

Submitter: Orphanet

Hailey-Hailey diseaseDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008218

Submitter: Ambry Genetics

Hailey-Hailey diseaseSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008218

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Hailey-Hailey diseaseAD

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 4939904; 5093171; 3978039; 2528572; 1554604; 1575528; 10615129; 15545997; 21623880; 21883398; 22124882; 22229453; 22607350; 22788811

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP2C1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 118

Inborn genetic diseasesTotal: 70

Familial benign pemphigusTotal: 58

ATP2C1-related disorderTotal: 30

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378687.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	21 clinvar	2 clinvar	30
missense	3 clinvar	6 clinvar	112 clinvar	2 clinvar	4 clinvar	127
nonsense	13 clinvar	3 clinvar	1 clinvar			17
start loss			1 clinvar			1
frameshift	17 clinvar	10 clinvar				27
splice donor/acceptor (+/-2bp)	7 clinvar	9 clinvar	12 clinvar			28
Total	40	28	133	23	6	230

Highest pathogenic variant AF is 0.00001314475

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 89 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001378687.1	RefSeq	NP_001365616.1	27	MANE Select
ENST00000510168.6	Ensembl	ENSP00000427461.1	27	MANE Select
NM_001001485.3	RefSeq	NP_001001485.1	27	Standard
NM_001001486.2	RefSeq	NP_001001486.1	28	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ion channel transport
Purine metabolism
Transport of small molecules
Ion transport by P-type ATPases

Biological Process

calcium ion transport
cellular calcium ion homeostasis
epidermis development
calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules
actin cytoskeleton reorganization

Molecular Function

calcium-transporting ATPase activity
ATP binding
proton-exporting ATPase activity, phosphorylative mechanism
manganese-transporting ATPase activity
metal ion binding

Cellular Component

Golgi membrane
Golgi apparatus
trans-Golgi network
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393221
Coding exons: 28
Length: 166118
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.67	280	514	0.544	0.0000257	6368
Missense (PolyPhen)		51	167.14	0.30513		2039
Synonymous	0.322	162	167	0.968	0.00000820	1873
Loss of Function	6.43	5	57.7	0.0867	0.00000298	685

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000079	0.000079	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of the calcium.;

Recessive Scores

pRec: 0.209

Intolerance Scores

LoFtool: 0.00903
RVIS EVS: -0.29
RVIS percentile EVS: 33.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.195

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium