ATP13A1

protein-coding

ATPase 13A1, the group of ATPase orphan transporters

Gene summary

Enables membrane protein dislocase activity. Involved in extraction of mislocalized protein from ER membrane. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

ATP13A

MANE transcript

NM_020410.3

Inheritance

ClinVar variants

U:196B:24

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr19:19,645,198-19,663,676

External References & Databases

Ensembl (ENSG00000105726)

Transcript & Mutation Effects

hg38 • Region Span ~18.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published: PMID:28940097 reports 1 proband from a consanguineous family with homozygous ATP13A1 NM_020410.2:c.1045G>A (missense) in intellectual disability cohort; limited ATP13A1-specific phenotypic/segregation detail; case-level (biallelic missense) = 0.1; segregation = 0; case-control = 0. PMID:30315573 reports 1 proband with homozygous ATP13A1 NM_020410.3:c.1639G>T;p.(Gly547Cys) in consanguinity-enriched ID cohort; limited ATP13A1-specific functional validation; case-level (biallelic missense) = 0.1; segregation = 0; case-control = 0. Published genetic evidence total = 0.2/12. Genetic evidence – our case: 1-year-old male with IUGR, microcephaly, cerebellar hypoplasia, multiple congenital anomalies (renal, cardiac, airway), positive consanguinity, one healthy sibling; homozygous frameshift NM_020410.3:c.604_611del;p.(Tyr202GlufsTer15) (predicted loss-of-function). Case-level (biallelic predicted null in AR model, consanguinity) = 1.0; segregation = 0; case-control = 0. Current case contribution = 1.0/12. Total genetic evidence (published + our case) = 1.2/12. Experimental evidence – Published: ATP13A1 encodes an ER P5A-ATPase involved in ER protein quality control and translocation; biochemical/functional cellular studies support gene function but are not disease-specific (PMID:36283413; PMID:28940097). Biochemical function/general cellular role = 0.5; no scored disease model or rescue specific to ATP13A1-NDD. Experimental evidence total = 0.5/6. Overall score = 1.7 points

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP13A1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 175

not providedTotal: 26

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020410.3. 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			3 clinvar	9 clinvar	6 clinvar	18
missense			178 clinvar	7 clinvar	2 clinvar	187
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	196	16	8	220

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020410.3	RefSeq	NP_065143.2	26	MANE Select
ENST00000357324.11	Ensembl	ENSP00000349877.6	26	MANE Select
ENST00000291503.9	Ensembl	ENSP00000291503.5	26	Standard
ENST00000455627.1	Ensembl	ENSP00000411891.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

cellular calcium ion homeostasis
biological_process
ion transmembrane transport
manganese ion transmembrane transport
ATP hydrolysis coupled cation transmembrane transport

Molecular Function

molecular_function
ATP binding
manganese-transporting ATPase activity
metal ion binding

Cellular Component

endoplasmic reticulum membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357324
Coding exons: 26
Length: 18496
Individuals with no LoFs: 125586
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125607
p: 0.0000836

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.66	526	728	0.722	0.0000470	7631
Missense (PolyPhen)		145	303.07	0.47843		3205
Synonymous	-0.197	337	332	1.01	0.0000233	2505
Loss of Function	5.82	10	57.8	0.173	0.00000309	619

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000067	0.000062	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates manganese transport into the endoplasmic reticulum. The ATPase activity is required for cellular manganese homeostasis. {ECO:0000269|PubMed:24392018}.;

Intolerance Scores

LoFtool: 0.129
RVIS EVS: -1.26
RVIS percentile EVS: 5.34

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.618

Gene Damage Prediction

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