ATP13A2

ATPase cation transporting 13A2, the group of ATPase orphan transporters

Basic information

Region (hg38): 1:16985957-17011928

Previous symbols: [ "PARK9" ]

Links

ENSG00000159363 ∙ NCBI:23400 ∙ OMIM:610513 ∙ HGNC:30213 ∙ Uniprot:Q9NQ11 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spastic paraplegia type 78 (Moderate), mode of inheritance: AR
• Kufor-Rakeb syndrome (Strong), mode of inheritance: AR
• autosomal recessive spastic paraplegia type 78 (Strong), mode of inheritance: AR
• parkinsonism due to ATP13A2 deficiency (Supportive), mode of inheritance: AR
• autosomal recessive spastic paraplegia type 78 (Supportive), mode of inheritance: AR
• Kufor-Rakeb syndrome (Moderate), mode of inheritance: AR
• Kufor-Rakeb syndrome (Definitive), mode of inheritance: AR
• Kufor-Rakeb syndrome (Strong), mode of inheritance: AR
• autosomal recessive spastic paraplegia type 78 (Strong), mode of inheritance: AR
• Kufor-Rakeb syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Kufor-Rakeb syndrome (Parkinson disease 9)	AR	Neurologic	In Kufor-Rakeb syndrome, response to levodopa has been documented	Neurologic	16964263; 17485642; 20310007; 22388936; 27217339

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP13A2 gene.

• Kufor-Rakeb syndrome;Autosomal recessive spastic paraplegia type 78 (385 variants)
• Autosomal recessive spastic paraplegia type 78;Kufor-Rakeb syndrome (356 variants)
• not provided (222 variants)
• Inborn genetic diseases (213 variants)
• Kufor-Rakeb syndrome (139 variants)
• not specified (38 variants)
• Autosomal recessive spastic paraplegia type 78 (23 variants)
• Neurodegeneration with brain iron accumulation (5 variants)
• ATP13A2-related condition (5 variants)
• ATP13A2-related disorders (2 variants)
• See cases (2 variants)
• Kufor-Rakeb syndrome;Autosomal recessive spastic paraplegia type 78;Parkinsonism due to ATP13A2 deficiency (1 variants)
• Spastic tetraparesis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP13A2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			11	168	7	186
missense		1	375	18	3	397
nonsense	11	6	2			19
start loss			1			1
frameshift	16	7	6			29
inframe indel			6			6
splice donor/acceptor (+/-2bp)		10	1			11
splice region	1		22	22	1	46
non coding			16	114	24	154
Total	27	24	418	300	34

Highest pathogenic variant AF is 0.0000329

Variants in ATP13A2

This is a list of pathogenic ClinVar variants found in the ATP13A2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-16985970-T-C		Kufor-Rakeb syndrome	Likely benign (Jun 14, 2016)
1-16985978-T-G		Kufor-Rakeb syndrome	Uncertain significance (Jan 13, 2018)
1-16985990-C-T		Kufor-Rakeb syndrome	Benign (Apr 01, 2024)
1-16986014-G-A		not specified	Uncertain significance (Jun 15, 2023)
1-16986039-G-A		Kufor-Rakeb syndrome	Uncertain significance (Jan 12, 2018)
1-16986063-A-C			Likely benign (Aug 01, 2022)
1-16986063-A-G		Kufor-Rakeb syndrome	Likely benign (Apr 01, 2024)
1-16986065-C-T			Uncertain significance (Nov 01, 2023)
1-16986066-G-A		Kufor-Rakeb syndrome • Autosomal recessive spastic paraplegia type 78;Kufor-Rakeb syndrome	Conflicting classifications of pathogenicity (Dec 01, 2022)
1-16986069-T-TC			Uncertain significance (Jan 01, 2020)
1-16986075-G-A		ATP13A2-related disorder	Likely benign (Mar 07, 2019)
1-16986076-G-A		Inborn genetic diseases	Uncertain significance (Nov 24, 2021)
1-16986081-G-C		Kufor-Rakeb syndrome • ATP13A2-related disorder	Benign/Likely benign (Jan 06, 2020)
1-16986083-G-A		Inborn genetic diseases	Uncertain significance (Aug 25, 2022)
1-16986091-G-A		Kufor-Rakeb syndrome • Kufor-Rakeb syndrome;Autosomal recessive spastic paraplegia type 78	Conflicting classifications of pathogenicity (Apr 01, 2024)
1-16986097-G-A		Kufor-Rakeb syndrome	Benign (Jul 17, 2018)
1-16986101-T-A		Kufor-Rakeb syndrome • ATP13A2-related disorder	Benign/Likely benign (Mar 01, 2024)
1-16986112-G-A		See cases	Uncertain significance (Apr 05, 2020)
1-16986142-G-A			Uncertain significance (Dec 01, 2017)
1-16986145-G-A			Uncertain significance (May 14, 2020)
1-16986163-T-C		Kufor-Rakeb syndrome	Uncertain significance (Jan 13, 2018)
1-16986172-T-C			Uncertain significance (Jan 01, 2024)
1-16986180-A-G		ATP13A2-related disorder	Likely benign (Feb 15, 2021)
1-16986197-G-A		Kufor-Rakeb syndrome	Uncertain significance (Apr 01, 2017)
1-16986204-G-A			Likely benign (Aug 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP13A2	protein_coding	protein_coding	ENST00000326735	29	25971

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.96e-9	1.00	125647	0	101	125748	0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	624	731	0.854	0.0000508	7465
Missense in Polyphen		186	241.28	0.7709		2622
Synonymous	-0.537	342	330	1.04	0.0000243	2564
Loss of Function	4.12	24	57.8	0.415	0.00000289	620

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000909	0.000902
Ashkenazi Jewish	0.00249	0.00248
East Asian	0.000273	0.000272
Finnish	0.000102	0.0000924
European (Non-Finnish)	0.000321	0.000316
Middle Eastern	0.000273	0.000272
South Asian	0.000201	0.000196
Other	0.000818	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATPase that plays a role in intracellular cation homeostasis and the maintenance of neuronal integrity (PubMed:22186024). Required for a proper lysosomal and mitochondrial maintenance (PubMed:22296644, PubMed:28137957). {ECO:0000269|PubMed:22186024, ECO:0000269|PubMed:22296644, ECO:0000269|PubMed:28137957}.
• Disease: DISEASE: Kufor-Rakeb syndrome (KRS) [MIM:606693]: A rare form of autosomal recessive juvenile or early-onset, levodopa-responsive parkinsonism. In addition to typical parkinsonian signs, clinical manifestations of Kufor-Rakeb syndrome include behavioral problems, facial tremor, pyramidal tract dysfunction, supranuclear gaze palsy, and dementia. {ECO:0000269|PubMed:16964263, ECO:0000269|PubMed:17485642, ECO:0000269|PubMed:18413573, ECO:0000269|PubMed:20683840, ECO:0000269|PubMed:20853184, ECO:0000269|PubMed:21542062, ECO:0000269|PubMed:22296644, ECO:0000269|PubMed:22388936, ECO:0000269|PubMed:22768177, ECO:0000269|PubMed:28137957}. Note=The disease is caused by mutations affecting the gene represented in this entry. KRS has also been referred to as neuronal ceroid lipofuscinosis 12 (CLN12), due to neuronal and glial lipofuscin deposits detected in the cortex, basal nuclei and cerebellum of some patients. {ECO:0000269|PubMed:22388936}.; DISEASE: Spastic paraplegia 78, autosomal recessive (SPG78) [MIM:617225]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:27217339, ECO:0000269|PubMed:28137957}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ion channel transport;Transport of small molecules;Ion transport by P-type ATPases (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.0289
• rvis_EVS: -1.16
• rvis_percentile_EVS: 6.1

Haploinsufficiency Scores

• pHI: 0.160
• hipred: Y
• hipred_score: 0.563
• ghis: 0.568

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.227

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atp13a2
• Phenotype: cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: atp13a2
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: cellular calcium ion homeostasis;cellular iron ion homeostasis;cellular zinc ion homeostasis;regulation of mitochondrion organization;regulation of macroautophagy;regulation of autophagosome size;cellular cation homeostasis;regulation of intracellular protein transport;ion transmembrane transport;cellular response to oxidative stress;protein autophosphorylation;positive regulation of protein secretion;regulation of endopeptidase activity;zinc ion homeostasis;cellular response to manganese ion;cellular response to zinc ion;extracellular exosome biogenesis;ATP hydrolysis coupled cation transmembrane transport;negative regulation of neuron death;polyamine transmembrane transport;regulation of autophagy of mitochondrion;positive regulation of exosomal secretion;regulation of chaperone-mediated autophagy;autophagosome organization;regulation of glucosylceramidase activity;regulation of lysosomal protein catabolic process;negative regulation of lysosomal protein catabolic process;peptidyl-aspartic acid autophosphorylation
• Cellular component: lysosome;lysosomal membrane;late endosome;multivesicular body;autophagosome;vesicle membrane;integral component of membrane;transport vesicle;vesicle;multivesicular body membrane;neuron projection;neuronal cell body;lysosomal lumen;integral component of lysosomal membrane
• Molecular function: protein binding;ATP binding;zinc ion binding;ATPase activity;cation-transporting ATPase activity;manganese ion binding;phosphatidic acid binding;phosphatidylinositol-3,5-bisphosphate binding;cupric ion binding