ATP13A5

Summary

ATP13A5 (ATPase 13A5, HGNC:31789) is a protein-coding gene on chromosome 3q29, encoding Probable cation-transporting ATPase 13A5 (Q4VNC0).

This gene encodes a member of the P5 subfamily of P-type transport ATPases. P-type ATPases form a large superfamily of cation and lipid pumps that transport inorganic cations and other substrates across cell membranes. P5 ATPases are localized to membranes of the endoplasmic reticulum (ER) and serve many important functions including transport of cargo proteins to the Golgi, glycosylation and cell wall biosynthesis, control of protein insertion orientation, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) degradation, and sensitivity to unfolded protein response (UPR) activators. The encoded protein is organized into three cytoplasmic domains (A, P, and N) and two membrane-embedded domains (T and S). The N-domain binds ATP and serves as a built-in protein kinase, which phosphorylates the P-domain. The A-domain is an intrinsic protein phosphatase, which dephosphorylates the P-domain once during each catalytic cycle.

Source: NCBI Gene 344905 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 176 total
• MANE Select transcript: NM_198505

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31789
Approved symbol	ATP13A5
Name	ATPase 13A5
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16025
Ensembl gene	ENSG00000187527
Ensembl biotype	protein_coding
OMIM	619119
Entrez	344905

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000342358, ENST00000446087, ENST00000488957, ENST00000495496

RefSeq mRNA: 1 — MANE Select: NM_198505 NM_198505

CCDS: CCDS33914

Canonical transcript exons

ENST00000342358 — 30 exons

Exon	Start	End
ENSE00001366297	193274789	193275302
ENSE00001490617	193314033	193314193
ENSE00001490618	193314972	193315096
ENSE00001490620	193318991	193319108
ENSE00001490621	193321681	193321837
ENSE00001490624	193326996	193327057
ENSE00001490625	193331123	193331311
ENSE00001490626	193333750	193333907
ENSE00001490627	193334929	193335099
ENSE00001490628	193343927	193344055
ENSE00001490630	193345003	193345075
ENSE00001490632	193351067	193351201
ENSE00001490635	193354127	193354196
ENSE00001490636	193362381	193362461
ENSE00001490638	193362567	193362637
ENSE00001490639	193363236	193363382
ENSE00001490640	193364107	193364280
ENSE00001598507	193378663	193378753
ENSE00002532138	193324864	193325014
ENSE00003466799	193307327	193307369
ENSE00003480980	193301211	193301307
ENSE00003482689	193311816	193311941
ENSE00003505297	193279366	193279454
ENSE00003509093	193289885	193290059
ENSE00003557010	193276750	193276830
ENSE00003624436	193310638	193310717
ENSE00003632791	193284914	193285116
ENSE00003656571	193322491	193322574
ENSE00003658222	193299131	193299203
ENSE00003662920	193305559	193305668

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 89.73.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0564 / max 25.1659, expressed in 15 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46157	0.0308	9
46156	0.0190	6
46155	0.0065	2

Top tissues by expression

235 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	89.73	gold quality
pancreatic ductal cell	CL:0002079	89.61	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.07	gold quality
buccal mucosa cell	CL:0002336	76.26	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.13	gold quality
upper arm skin	UBERON:0004263	73.99	gold quality
nasal cavity mucosa	UBERON:0001826	72.93	gold quality
skin of leg	UBERON:0001511	72.05	gold quality
zone of skin	UBERON:0000014	70.69	gold quality
skin of abdomen	UBERON:0001416	70.18	gold quality
amygdala	UBERON:0001876	67.27	gold quality
lower esophagus mucosa	UBERON:0035834	67.11	gold quality
right lobe of thyroid gland	UBERON:0001119	67.04	gold quality
nucleus accumbens	UBERON:0001882	67.03	gold quality
epithelium of mammary gland	UBERON:0003244	66.57	silver quality
putamen	UBERON:0001874	66.48	gold quality
anterior cingulate cortex	UBERON:0009835	66.38	gold quality
mammary duct	UBERON:0001765	66.32	silver quality
caudate nucleus	UBERON:0001873	65.86	gold quality
skin of hip	UBERON:0001554	65.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	65.06	gold quality
ileal mucosa	UBERON:0000331	64.46	silver quality
right frontal lobe	UBERON:0002810	64.43	gold quality
left lobe of thyroid gland	UBERON:0001120	64.29	gold quality
thoracic mammary gland	UBERON:0005200	64.17	gold quality
tibia	UBERON:0000979	64.09	silver quality
mammary gland	UBERON:0001911	64.00	gold quality
parotid gland	UBERON:0001831	63.91	silver quality
Brodmann (1909) area 9	UBERON:0013540	63.90	gold quality
thyroid gland	UBERON:0002046	63.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.33

Regulation

Is transcription factor: no

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-28b4.8	ENSDARG00000002840
danio_rerio	atp1a3a	ENSDARG00000018259
danio_rerio	atp2b2	ENSDARG00000063433
danio_rerio	atp1a3b	ENSDARG00000104139
mus_musculus	Atp13a5	ENSMUSG00000048939
rattus_norvegicus	Atp13a5	ENSRNOG00000024127
drosophila_melanogaster	anne	FBGN0052000
drosophila_melanogaster	SPoCk	FBGN0052451
drosophila_melanogaster	CG45062	FBGN0266432
drosophila_melanogaster	CG45063	FBGN0266433
caenorhabditis_elegans		WBGENE00000834
caenorhabditis_elegans	pmr-1	WBGENE00004063
caenorhabditis_elegans		WBGENE00012341
caenorhabditis_elegans		WBGENE00015338
caenorhabditis_elegans		WBGENE00015660

Paralogs (21): ATP2C1 (ENSG00000017260), ATP1A2 (ENSG00000018625), ATP2B4 (ENSG00000058668), ATP2C2 (ENSG00000064270), ATP2B3 (ENSG00000067842), ATP2B1 (ENSG00000070961), ATP2A3 (ENSG00000074370), ATP12A (ENSG00000075673), ATP1A3 (ENSG00000105409), ATP4A (ENSG00000105675), ATP13A1 (ENSG00000105726), ATP7B (ENSG00000123191), ATP13A4 (ENSG00000127249), ATP1A4 (ENSG00000132681), ATP13A3 (ENSG00000133657), ATP2B2 (ENSG00000157087), ATP13A2 (ENSG00000159363), ATP1A1 (ENSG00000163399), ATP7A (ENSG00000165240), ATP2A2 (ENSG00000174437), ATP2A1 (ENSG00000196296)

Protein

Protein identifiers

Probable cation-transporting ATPase 13A5 — Q4VNC0 (reviewed: Q4VNC0)

Alternative names: P5-ATPase isoform 5

All UniProt accessions (2): C9JPQ4, Q4VNC0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.

RefSeq proteins (1): NP_940907* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001757	P_typ_ATPase	Family
IPR004014	ATPase_P-typ_cation-transptr_N	Domain
IPR006544	P-type_TPase_V	Family
IPR008250	ATPase_P-typ_transduc_dom_A_sf	Homologous_superfamily
IPR018303	ATPase_P-typ_P_site	PTM
IPR023214	HAD_sf	Homologous_superfamily
IPR023298	ATPase_P-typ_TM_dom_sf	Homologous_superfamily
IPR023299	ATPase_P-typ_cyto_dom_N	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR044492	P_typ_ATPase_HD_dom	Domain
IPR047819	P5A-ATPase_N	Domain
IPR047821	P5B-type_ATPase	Family
IPR059000	ATPase_P-type_domA	Domain

Pfam: PF00122, PF00690, PF12409, PF13246

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (24 total): transmembrane region 10, sequence variant 6, glycosylation site 3, binding site 2, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4VNC0-F1	78.94	0.21

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 486 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (2): 850; 854

Glycosylation sites (3): 540, 669, 819

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-382551	Transport of small molecules
R-HSA-983712	Ion channel transport

MSigDB gene sets: 64 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_LATE_ENDOSOME_MEMBRANE, LEIN_ASTROCYTE_MARKERS, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOMF_ACTIVE_MONOATOMIC_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ATP_HYDROLYSIS_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSPORTER_ACTIVITY

GO Biological Process (5): intracellular calcium ion homeostasis (GO:0006874), monoatomic ion transmembrane transport (GO:0034220), polyamine transmembrane transport (GO:1902047), transmembrane transport (GO:0055085), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (9): ATP binding (GO:0005524), polyamine transmembrane transporter activity (GO:0015203), P-type ion transporter activity (GO:0015662), ATP hydrolysis activity (GO:0016887), ATPase-coupled monoatomic cation transmembrane transporter activity (GO:0019829), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), transporter activity (GO:0005215), P-type transmembrane transporter activity (GO:0140358)

GO Cellular Component (3): plasma membrane (GO:0005886), late endosome membrane (GO:0031902), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transport	2
ATPase-coupled transmembrane transporter activity	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
monoatomic ion transport	1
polyamine transport	1
transport	1
cellular process	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transmembrane transporter activity	1
polyamine transmembrane transport	1
P-type transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
monoatomic cation transmembrane transporter activity	1
active monoatomic ion transmembrane transporter activity	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
membrane	1
cell periphery	1
late endosome	1
endosome membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP13A5	ABCC9	O60706	465
ATP13A5	FAM194C	Q8ND61	420
ATP13A5	CLDN17	P56750	364
ATP13A5	OR13F1	Q8NGS4	363
ATP13A5	ATP13A1	Q9HD20	358
ATP13A5	H6PD	O95479	351
ATP13A5	OR2C1	O95371	349
ATP13A5	OR10G4	Q8NGN3	348
ATP13A5	GAK	O14976	334
ATP13A5	TEX261	Q6UWH6	330
ATP13A5	PATL2	C9JE40	321
ATP13A5	SLC6A20	Q9NP91	321
ATP13A5	ADGRL4	Q9HBW9	316
ATP13A5	C12orf42	Q96LP6	310
ATP13A5	ITGB1BP1	O14713	307
ATP13A5	SLC9B2	Q86UD5	307

IntAct

0 interactions, top by confidence:

BioGRID (1): ATP13A5 (Proximity Label-MS)

ESM2 similar proteins: A3FIN4, D3K0R6, D4AA47, O14072, O23087, O43520, O60423, O75185, O94296, P22189, P23634, P39524, P54678, P57709, P90747, P98194, P98196, P98197, P98198, P98199, P98204, P98205, Q09891, Q10309, Q148W0, Q21286, Q27533, Q3TYU2, Q42883, Q4VNC0, Q4VNC1, Q5BL50, Q5XF90, Q5ZKB7, Q64542, Q6DFW5, Q6Q477, Q6UQ17, Q7XB51, Q8NB49

Diamond homologs: O14022, O74431, P0ABB8, P0ABB9, P22036, P54211, Q12697, Q21286, Q27533, Q3TYU2, Q4VNC0, Q4VNC1, Q5XF89, Q5XF90, Q5ZKB7, Q95JN5, Q9CTG6, Q9H7F0, Q9NQ11, O14072, P13587, P39986, P90747, Q01896, Q04956, Q12691, Q9EPE9, Q9HD20, P22180, P23980, P54679, Q08435, Q08436, Q43128, Q58623, Q9LV11, Q9LY32, Q9SH76, Q9SU58, P57698

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

176 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	156
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4965 predictions. Top by Δscore:

Variant	Effect	Δscore
3:193276831:C:CC	acceptor_gain	1.0000
3:193300945:C:CT	acceptor_gain	1.0000
3:193310636:A:AC	donor_gain	1.0000
3:193310637:C:CT	donor_gain	1.0000
3:193310718:C:CC	acceptor_gain	1.0000
3:193314028:CTCA:C	donor_loss	1.0000
3:193314031:A:AC	donor_gain	1.0000
3:193314031:ACT:A	donor_loss	1.0000
3:193314032:C:A	donor_loss	1.0000
3:193314032:C:CC	donor_gain	1.0000
3:193314032:CTTT:C	donor_gain	1.0000
3:193314035:T:A	donor_gain	1.0000
3:193314039:C:A	donor_gain	1.0000
3:193314191:CAC:C	acceptor_gain	1.0000
3:193314192:ACC:A	acceptor_loss	1.0000
3:193314194:CT:C	acceptor_loss	1.0000
3:193314195:T:A	acceptor_loss	1.0000
3:193315099:T:C	acceptor_gain	1.0000
3:193315106:C:CT	acceptor_gain	1.0000
3:193319109:C:CC	acceptor_gain	1.0000
3:193322486:CATA:C	donor_loss	1.0000
3:193322489:ACCT:A	donor_loss	1.0000
3:193322490:C:CG	donor_loss	1.0000
3:193322490:CCTTA:C	donor_gain	1.0000
3:193322494:A:AC	donor_gain	1.0000
3:193322495:C:CC	donor_gain	1.0000
3:193322495:CTGG:C	donor_gain	1.0000
3:193322571:TTTT:T	acceptor_gain	1.0000
3:193322572:TTT:T	acceptor_gain	1.0000
3:193322573:TT:T	acceptor_gain	1.0000

AlphaMissense

7990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:193331127:T:A	D486V	0.998
3:193331127:T:G	D486A	0.998
3:193307334:T:G	D854A	0.997
3:193331124:T:A	K487I	0.997
3:193307333:G:C	D854E	0.996
3:193307333:G:T	D854E	0.996
3:193310662:A:G	L834P	0.995
3:193310692:G:T	A824E	0.995
3:193314190:T:A	D721V	0.995
3:193314190:T:G	D721A	0.995
3:193321724:T:A	K624N	0.995
3:193321724:T:G	K624N	0.995
3:193321796:A:C	F600L	0.995
3:193321796:A:T	F600L	0.995
3:193321798:A:G	F600L	0.995
3:193327047:A:G	L491P	0.995
3:193331123:T:A	K487N	0.995
3:193331123:T:G	K487N	0.995
3:193331134:A:G	C484R	0.995
3:193331139:A:G	L482P	0.995
3:193305655:G:T	A861D	0.994
3:193307334:T:A	D854V	0.994
3:193307335:C:G	D854H	0.994
3:193314175:G:T	A726D	0.994
3:193314176:C:G	A726P	0.994
3:193314191:C:G	D721H	0.994
3:193327047:A:T	L491H	0.994
3:193331125:T:G	K487Q	0.994
3:193331128:C:G	D486H	0.994
3:193335077:C:A	K322N	0.994

dbSNP variants (sampled 300 via entrez): RS1000067833 (3:193296895 A>C,G), RS1000078886 (3:193296610 A>G,T), RS1000088605 (3:193303665 G>A), RS1000096110 (3:193277584 C>A,G), RS1000188346 (3:193340222 G>A), RS1000296557 (3:193309626 G>T), RS1000300791 (3:193303478 G>T), RS1000304535 (3:193340488 G>A,T), RS1000307646 (3:193322737 C>T), RS1000308285 (3:193303726 C>T), RS1000318402 (3:193364152 G>C), RS1000352688 (3:193346054 A>G), RS1000420686 (3:193303505 ATAATG>A), RS1000451684 (3:193285516 G>A), RS1000473039 (3:193380704 C>A)

Disease associations

OMIM: gene MIM:619119 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009885_1	Salivary metabolite levels	4.000000e-14
GCST012489_113	Heel bone mineral density x serum urate levels interaction	2.000000e-10
GCST90013658_2	Myeloperoxidase-DNA complexes	4.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010637	salivary metabolite measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0011039	myeloperoxidase (MPO)-DNA complex measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — P5 P-type ATPases: Mn²⁺-ATPases

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
geldanamycin	increases expression	1
CGP 52608	increases reaction, affects binding	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Allergens	increases expression	1
Benzo(a)pyrene	affects methylation	1
Mercuric Chloride	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.