ATP13A3

Summary

ATP13A3 (ATPase 13A3, HGNC:24113) is a protein-coding gene on chromosome 3q29, encoding Polyamine-transporting ATPase 13A3 (Q9H7F0). ATP-driven pump involved in endocytosis-dependent polyamine transport.

ATP13A3 is a member of the P-type ATPase family of proteins that transport a variety of cations across membranes. Other P-type ATPases include ATP7B (MIM 606882) and ATP7A (MIM 300011).

Source: NCBI Gene 79572 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary arterial hypertension (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 322 total — 8 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_001367549

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24113
Approved symbol	ATP13A3
Name	ATPase 13A3
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	AFURS1
Ensembl gene	ENSG00000133657
Ensembl biotype	protein_coding
OMIM	610232
Entrez	79572

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 23 protein_coding, 10 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000429136, ENST00000439040, ENST00000461660, ENST00000485194, ENST00000492983, ENST00000642744, ENST00000645319, ENST00000645538, ENST00000645621, ENST00000685123, ENST00000687055, ENST00000690382, ENST00000690408, ENST00000690810, ENST00000691700, ENST00000856972, ENST00000856973, ENST00000856974, ENST00000856975, ENST00000856976, ENST00000920212, ENST00000920213, ENST00000920214, ENST00000920215, ENST00000920216, ENST00000920217, ENST00000920218, ENST00000963858, ENST00000963859, ENST00000963860, ENST00000963861, ENST00000963862, ENST00000963863, ENST00000963864

RefSeq mRNA: 3 — MANE Select: NM_001367549 NM_001367549, NM_001374836, NM_024524

CCDS: CCDS43187, CCDS93438

Canonical transcript exons

ENST00000645319 — 34 exons

Exon	Start	End
ENSE00000910421	194427075	194427252
ENSE00000910425	194430072	194430181
ENSE00000910426	194430273	194430315
ENSE00000910427	194430943	194431022
ENSE00000910429	194431717	194431892
ENSE00001126585	194428845	194428917
ENSE00001225014	194419879	194419967
ENSE00001225019	194425342	194425529
ENSE00001291572	194444725	194444786
ENSE00001293270	194437095	194437215
ENSE00001295437	194438856	194438972
ENSE00001312954	194433772	194433896
ENSE00001317209	194446927	194447115
ENSE00001318784	194441311	194441461
ENSE00001330252	194437311	194437464
ENSE00001359883	194429678	194429774
ENSE00001413149	194413759	194413839
ENSE00001649446	194485794	194485835
ENSE00001737784	194412199	194412288
ENSE00001741459	194402677	194406116
ENSE00002441138	194457094	194457174
ENSE00002450796	194455893	194455962
ENSE00002451489	194459789	194459971
ENSE00002454845	194437556	194437573
ENSE00002455290	194459471	194459541
ENSE00002482162	194454258	194454392
ENSE00002483616	194453706	194453778
ENSE00002496702	194460658	194460831
ENSE00002688034	194462140	194462236
ENSE00003529576	194431104	194431226
ENSE00003588865	194447852	194448009
ENSE00003643055	194448457	194448636
ENSE00003651339	194450145	194450276
ENSE00003829318	194486566	194487002

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.5949 / max 671.6247, expressed in 1820 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46219	33.5811	1813
46218	14.5432	1671
46217	3.4370	1084
46206	1.6386	621
46210	0.5639	201
46202	0.4253	178
46220	0.2774	74
46207	0.0611	28
46208	0.0496	22
46209	0.0175	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	97.96	gold quality
secondary oocyte	CL:0000655	97.15	gold quality
amniotic fluid	UBERON:0000173	97.04	gold quality
cartilage tissue	UBERON:0002418	97.01	gold quality
palpebral conjunctiva	UBERON:0001812	96.96	gold quality
colonic epithelium	UBERON:0000397	96.54	gold quality
germinal epithelium of ovary	UBERON:0001304	96.09	gold quality
choroid plexus epithelium	UBERON:0003911	96.04	gold quality
parietal pleura	UBERON:0002400	95.91	gold quality
islet of Langerhans	UBERON:0000006	95.77	gold quality
pleura	UBERON:0000977	95.50	gold quality
visceral pleura	UBERON:0002401	95.21	gold quality
epithelium of nasopharynx	UBERON:0001951	95.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.00	gold quality
blood vessel layer	UBERON:0004797	94.84	gold quality
endometrium epithelium	UBERON:0004811	94.58	gold quality
adrenal tissue	UBERON:0018303	94.54	gold quality
gingival epithelium	UBERON:0001949	94.39	gold quality
liver	UBERON:0002107	94.28	gold quality
tibia	UBERON:0000979	94.11	gold quality
right lung	UBERON:0002167	94.06	gold quality
bronchial epithelial cell	CL:0002328	93.90	gold quality
placenta	UBERON:0001987	93.89	gold quality
thyroid gland	UBERON:0002046	93.88	gold quality
oocyte	CL:0000023	93.72	gold quality
left lobe of thyroid gland	UBERON:0001120	93.70	gold quality
lower lobe of lung	UBERON:0008949	93.62	gold quality
pigmented layer of retina	UBERON:0001782	93.60	gold quality
right coronary artery	UBERON:0001625	93.45	gold quality
renal medulla	UBERON:0000362	93.39	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	39.53
E-GEOD-124858	no	743.50
E-MTAB-9689	no	197.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

187 targeting ATP13A3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170

Literature-anchored findings (GeneRIF, showing 4)

• Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in heritable pulmonary arterial hypertension. (PMID:29650961)
• In addition to EIF2AK4, which has been already suggested to be associated with pulmonary veno-occlusive disease, we identified the novel candidate genes ATP13A3, CD248, EFCAB4B, involved in lung vascular remodeling that represent reliable drivers contributing to the disease according to their biological functions/inheritance patterns (PMID:30679663)
• Pairing a prognostic target with potential therapeutic strategy for head and neck cancer. (PMID:33091845)
• ATP13A3 variants promote pulmonary arterial hypertension by disrupting polyamine transport. (PMID:38626311)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp13a3	ENSDARG00000076622
mus_musculus	Atp13a3	ENSMUSG00000022533
rattus_norvegicus	Atp13a3	ENSRNOG00000066681
drosophila_melanogaster	SPoCk	FBGN0052451
drosophila_melanogaster	CG45062	FBGN0266432
drosophila_melanogaster	CG45063	FBGN0266433
caenorhabditis_elegans		WBGENE00000834
caenorhabditis_elegans	pmr-1	WBGENE00004063
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), ATP2B2 (ENSG00000157087), ATP13A2 (ENSG00000159363), ATP1A1 (ENSG00000163399), ATP7A (ENSG00000165240), ATP2A2 (ENSG00000174437), ATP13A5 (ENSG00000187527), ATP2A1 (ENSG00000196296)

Protein

Protein identifiers

Polyamine-transporting ATPase 13A3 — Q9H7F0 (reviewed: Q9H7F0)

Alternative names: ATPase family homolog up-regulated in senescence cells 1, Putrescine transporting ATPase

All UniProt accessions (3): A0A2R8Y635, A0A2R8YDN7, Q9H7F0

UniProt curated annotations — full annotation on UniProt →

Function. ATP-driven pump involved in endocytosis-dependent polyamine transport. Uses ATP as an energy source to transfer polyamine precursor putrescine from the endosomal compartment to the cytosol.

Subcellular location. Recycling endosome membrane. Early endosome membrane. Late endosome membrane.

Tissue specificity. Broadly expressed.

Disease relevance. Pulmonary hypertension, primary, 5 (PPH5) [MIM:265400] A form of primary pulmonary hypertension, a disease defined by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. Primary pulmonary hypertension exhibits incomplete penetrance, sex bias and variable age of onset, both within and between families. PPH5 is an autosomal recessive form characterized by the onset in infancy. Death in early childhood is common. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by polyamine biosynthesis inhibitor, difluoromethylornithine (DFMO).

Miscellaneous. Dubious isoform produced through aberrant splice sites.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H7F0-1	1	yes
Q9H7F0-2	2

RefSeq proteins (3): NP_001354478, NP_001361765, NP_078800 (=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:

• putrescine(out) + ATP + H2O = putrescine(in) + ADP + phosphate + H(+) (RHEA:29995)

UniProt features (48 total): topological domain 12, transmembrane region 10, binding site 9, sequence conflict 5, splice variant 4, modified residue 2, sequence variant 2, chain 1, intramembrane region 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7F0-F1	77.96	0.22

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): 498 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (9): 498–500; 498; 500; 628; 684; 750; 883–887; 883; 887

Post-translational modifications (2): 98, 817

Mutagenesis-validated functional residues (1):

Position	Phenotype
498	impairs the transport activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 287 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, PUJANA_CHEK2_PCC_NETWORK, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, WEI_MYCN_TARGETS_WITH_E_BOX, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, HSIAO_LIVER_SPECIFIC_GENES, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, OCT1_06, GENTILE_UV_HIGH_DOSE_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_ORGANIC_CATION_TRANSPORT, SENESE_HDAC1_TARGETS_UP

GO Biological Process (5): intracellular calcium ion homeostasis (GO:0006874), polyamine transmembrane transport (GO:1902047), putrescine transport (GO:0015847), transmembrane transport (GO:0055085), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (10): ATP binding (GO:0005524), polyamine transmembrane transporter activity (GO:0015203), ABC-type putrescine transporter activity (GO:0015594), 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), P-type transmembrane transporter activity (GO:0140358), nucleotide binding (GO:0000166), transporter activity (GO:0005215)

GO Cellular Component (5): membrane (GO:0016020), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), recycling endosome membrane (GO:0055038), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome membrane	3
polyamine transport	2
ATPase-coupled transmembrane transporter activity	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
transmembrane 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
ABC-type polyamine transporter activity	1
putrescine transmembrane transporter activity	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
cellular anatomical structure	1
early endosome	1
late endosome	1
recycling endosome	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1502 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP13A3	ATP7B	P35670	779
ATP13A3	ATP7A	Q04656	697
ATP13A3	GDF2	Q9UK05	689
ATP13A3	TBX4	P57082	665
ATP13A3	KCNK3	O14649	652
ATP13A3	EIF2AK4	Q9P2K8	636
ATP13A3	ACVRL1	P37023	588
ATP13A3	BMPR2	Q13873	535
ATP13A3	AQP1	P29972	534
ATP13A3	SLC18B1	Q6NT16	533
ATP13A3	SOX17	Q9H6I2	518
ATP13A3	SMAD9	O15198	515
ATP13A3	TMEM44	Q2T9K0	479
ATP13A3	SLC35F1	Q5T1Q4	460
ATP13A3	KCNA5	P22460	408

IntAct

148 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
AUP1	APOB	psi-mi:“MI:0914”(association)	0.610
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
rep	ATP5MG	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
GPR17	IPO8	psi-mi:“MI:0914”(association)	0.530
AGPAT3	ENDOD1	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
GPRC5B	STXBP3	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350

BioGRID (220): ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS), ATP13A3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4J6, D4ABB8, F1Q4S1, G5EBH1, O14072, O43520, O43861, O70228, O75110, P09626, P19156, P20648, P27112, P40527, P50996, P57792, P90747, P98195, P98196, P98197, P98198, P98199, Q10309, Q27533, Q3TYU2, Q4VNC1, Q4WYP6, Q5XF89, Q5XF90, Q5ZKB7, Q64436, Q6DFW5, Q8NB49, Q92126, Q93084, Q95JN5, Q9EPE9, Q9H7F0, Q9HD20, Q9LI83

Diamond homologs: O14022, O74431, P0ABB8, P0ABB9, P22036, P54211, Q12697, Q21286, Q27533, Q3TYU2, Q4VNC0, Q4VNC1, Q5XF89, Q5XF90, Q5ZKB7, Q95JN5, Q9CTG6, Q9H7F0, Q9NQ11, A0A143ZZK9, A0R3Y2, B9QMJ0, P0A505, P35597, P90747, P9WPT0, P9WPT1, Q08853, Q4WYP6, Q95050, Q9EPE9, Q9HD20, P05030, P07038, P09627, P11718, P12522, P15718, P19456, P19657

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 183 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
transmembrane transport	7	7.6×	8e-03
positive regulation of cytosolic calcium ion concentration	10	7.5×	4e-04
phospholipase C-activating G protein-coupled receptor signaling pathway	8	6.8×	6e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	9	6.5×	3e-03
G protein-coupled receptor signaling pathway	19	4.4×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	155
Likely benign	64
Benign	51

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1195990	NM_001367549.1(ATP13A3):c.2549dup (p.Met850fs)	Pathogenic
1195992	NM_001367549.1(ATP13A3):c.3079dup (p.Trp1027fs)	Pathogenic
1707428	GRCh37/hg19 3q27.1-29(chr3:183498520-197851986)x3	Pathogenic
1946124	NM_001367549.1(ATP13A3):c.3328dup (p.Ser1110fs)	Pathogenic
3682847	NM_001367549.1(ATP13A3):c.2367G>A (p.Trp789Ter)	Pathogenic
4706084	NM_001367549.1(ATP13A3):c.3341dup (p.Leu1114fs)	Pathogenic
4737583	NM_001367549.1(ATP13A3):c.3402+1G>T	Pathogenic
57870	GRCh38/hg38 3q27.3-29(chr3:187446231-195029133)x1	Pathogenic
1195989	NM_001367549.1(ATP13A3):c.2563G>A (p.Val855Met)	Likely pathogenic
1195991	NM_001367549.1(ATP13A3):c.2227C>T (p.Arg743Cys)	Likely pathogenic
2580342	GRCh37/hg19 3q29(chr3:193343827-194599635)x1	Likely pathogenic

SpliceAI

5006 predictions. Top by Δscore:

Variant	Effect	Δscore
3:194427073:A:AC	donor_gain	1.0000
3:194427074:C:CC	donor_gain	1.0000
3:194427074:CT:C	donor_gain	1.0000
3:194427258:T:TC	acceptor_gain	1.0000
3:194428836:AATAC:A	donor_loss	1.0000
3:194428837:ATACT:A	donor_loss	1.0000
3:194428838:TACT:T	donor_loss	1.0000
3:194428839:AC:A	donor_loss	1.0000
3:194428840:CTCAC:C	donor_loss	1.0000
3:194428841:T:TA	donor_loss	1.0000
3:194428842:CA:C	donor_loss	1.0000
3:194428843:A:AC	donor_gain	1.0000
3:194428843:A:C	donor_loss	1.0000
3:194428844:C:CA	donor_gain	1.0000
3:194428844:C:G	donor_loss	1.0000
3:194428844:CT:C	donor_gain	1.0000
3:194428915:GATC:G	acceptor_loss	1.0000
3:194428916:ATC:A	acceptor_loss	1.0000
3:194428917:TCTA:T	acceptor_loss	1.0000
3:194428918:C:CC	acceptor_gain	1.0000
3:194429669:AATAC:A	donor_loss	1.0000
3:194429670:ATACT:A	donor_loss	1.0000
3:194429671:TACTC:T	donor_loss	1.0000
3:194429672:ACTCA:A	donor_loss	1.0000
3:194429673:C:CA	donor_loss	1.0000
3:194429674:T:TA	donor_loss	1.0000
3:194429675:CACA:C	donor_loss	1.0000
3:194429676:A:AC	donor_gain	1.0000
3:194429676:AC:A	donor_loss	1.0000
3:194429677:C:CT	donor_gain	1.0000

AlphaMissense

8300 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:194428888:A:C	F968L	1.000
3:194428888:A:T	F968L	1.000
3:194428890:A:G	F968L	1.000
3:194447051:A:T	L458H	1.000
3:194454347:A:G	W226R	1.000
3:194454347:A:T	W226R	1.000
3:194428877:T:A	D972V	0.999
3:194428877:T:C	D972G	0.999
3:194428877:T:G	D972A	0.999
3:194428886:A:G	L969P	0.999
3:194429696:A:C	S952R	0.999
3:194429696:A:T	S952R	0.999
3:194429698:T:G	S952R	0.999
3:194429714:G:C	S946R	0.999
3:194429714:G:T	S946R	0.999
3:194429716:T:G	S946R	0.999
3:194429766:C:G	R929P	0.999
3:194429769:C:T	G928D	0.999
3:194429770:C:G	G928R	0.999
3:194437409:C:G	R634P	0.999
3:194437426:A:C	F628L	0.999
3:194437426:A:T	F628L	0.999
3:194437428:A:G	F628L	0.999
3:194438911:A:T	V591D	0.999
3:194441313:A:G	W570R	0.999
3:194441313:A:T	W570R	0.999
3:194446931:T:A	D498V	0.999
3:194446931:T:G	D498A	0.999
3:194447043:C:G	A461P	0.999
3:194447045:G:T	A460D	0.999

dbSNP variants (sampled 300 via entrez): RS1000026780 (3:194439936 T>C), RS1000045581 (3:194424156 C>T), RS1000094278 (3:194482082 A>T), RS1000147145 (3:194480682 T>C), RS1000203246 (3:194415452 C>T), RS1000245739 (3:194411305 T>C), RS1000265941 (3:194456784 G>A,C), RS1000275307 (3:194415196 G>A,C), RS1000314154 (3:194448776 T>C), RS1000327747 (3:194428417 T>C), RS1000374923 (3:194490380 C>A,T), RS1000403969 (3:194467247 TAGA>T), RS1000434458 (3:194422275 T>C), RS1000450010 (3:194465080 C>A,G), RS1000501902 (3:194464793 T>G)

Disease associations

OMIM: gene MIM:610232 | disease phenotypes: MIM:265400, MIM:165500

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary arterial hypertension	Definitive	Semidominant
pulmonary hypertension, primary, 5	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pulmonary arterial hypertension	Definitive	SD

Mondo (4): pulmonary hypertension, primary, 5 (MONDO:0009935), pulmonary arterial hypertension (MONDO:0015924), breast ductal adenocarcinoma (MONDO:0005590), autosomal dominant optic atrophy, classic form (MONDO:0008134)

Orphanet (3): Pulmonary arterial hypertension (Orphanet:182090), Idiopathic/heritable pulmonary arterial hypertension (Orphanet:422), Autosomal dominant optic atrophy, classic form (Orphanet:98673)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005976_3	White blood cell count (basophil)	4.000000e-08
GCST90002403_559	Red blood cell count	8.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005090	basophil count
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
C564862	Pulmonary Hypertension, Primary, Autosomal Recessive (supp.)

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

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
bisphenol S	affects cotreatment, increases methylation, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Estradiol	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
sodium arsenite	increases expression	1
3-deazaadenosine	decreases reaction, increases expression, increases methylation	1
thallium acetate	decreases reaction, increases expression, increases methylation, affects reaction, increases stability	1
diallyl trisulfide	increases expression	1
tamibarotene	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1KN	Abcam HeLa ATP13A3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
NCT03236818	PHASE4	UNKNOWN	Goal Oriented Strategy to Preserve Ejection Fraction Trial
NCT03344159	PHASE4	COMPLETED	Spironolactone Therapy in Chronic Stable Right HF Trial