ATP9A

Summary

ATP9A (ATPase phospholipid transporting 9A, HGNC:13540) is a protein-coding gene on chromosome 20q13.2, encoding Probable phospholipid-transporting ATPase IIA (O75110). Plays a role in regulating membrane trafficking of cargo proteins, namely endosome to plasma membrane recycling, probably acting through RAB5 and RAB11 activation.

Enables protease binding activity. Involved in negative regulation of exosomal secretion; regulation of endocytic recycling; and regulation of retrograde transport, endosome to Golgi. Located in several cellular components, including endosome; perinuclear region of cytoplasm; and trans-Golgi network membrane. Implicated in neurodevelopmental disorder with poor growth and behavioral abnormalities.

Source: NCBI Gene 10079 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with poor growth and behavioral abnormalities (Strong, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 179 total — 9 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 40
• MANE Select transcript: NM_006045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13540
Approved symbol	ATP9A
Name	ATPase phospholipid transporting 9A
Location	20q13.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0611, ATPIIA
Ensembl gene	ENSG00000054793
Ensembl biotype	protein_coding
OMIM	609126
Entrez	10079

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000311637, ENST00000338821, ENST00000477492, ENST00000892203

RefSeq mRNA: 1 — MANE Select: NM_006045 NM_006045

CCDS: CCDS33489

Canonical transcript exons

ENST00000338821 — 28 exons

Exon	Start	End
ENSE00000662716	51604817	51605020
ENSE00000662717	51607527	51607584
ENSE00000662718	51608518	51608626
ENSE00000662719	51610101	51610165
ENSE00000662720	51613677	51613832
ENSE00000662722	51618662	51618806
ENSE00000662727	51628980	51629072
ENSE00000662733	51676132	51676208
ENSE00001202669	51689064	51689139
ENSE00001202725	51656938	51657150
ENSE00001258256	51712966	51713074
ENSE00001258329	51627600	51627683
ENSE00001258341	51639343	51639504
ENSE00001258355	51669997	51670109
ENSE00001258363	51671115	51671257
ENSE00001258372	51674153	51674313
ENSE00001258432	51625192	51625362
ENSE00001258451	51596514	51601347
ENSE00001313692	51622074	51622172
ENSE00001317267	51690739	51690819
ENSE00001327070	51696093	51696144
ENSE00001329340	51694008	51694102
ENSE00001607998	51617490	51617554
ENSE00001702257	51697424	51697482
ENSE00001804656	51618954	51619043
ENSE00001950931	51768302	51768390
ENSE00003461776	51725819	51725932
ENSE00003633411	51729834	51729978

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.4755 / max 283.6352, expressed in 1508 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187956	7.3580	1314
187961	4.3818	1108
187962	2.5718	761
187957	1.8409	846
187960	0.4218	212
187953	0.2068	86
187952	0.1793	70
187959	0.1664	87
187939	0.1564	57
187951	0.0548	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.03	gold quality
orbitofrontal cortex	UBERON:0004167	98.81	gold quality
medial globus pallidus	UBERON:0002477	98.50	gold quality
entorhinal cortex	UBERON:0002728	98.23	gold quality
globus pallidus	UBERON:0001875	98.20	gold quality
superior frontal gyrus	UBERON:0002661	98.18	gold quality
postcentral gyrus	UBERON:0002581	98.09	gold quality
parietal lobe	UBERON:0001872	98.07	gold quality
cortical plate	UBERON:0005343	98.07	gold quality
paraflocculus	UBERON:0005351	97.99	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.98	gold quality
frontal pole	UBERON:0002795	97.80	gold quality
lateral globus pallidus	UBERON:0002476	97.64	gold quality
cerebellar vermis	UBERON:0004720	97.63	gold quality
pancreatic ductal cell	CL:0002079	97.50	silver quality
middle frontal gyrus	UBERON:0002702	97.46	gold quality
superior vestibular nucleus	UBERON:0007227	97.42	gold quality
substantia nigra pars compacta	UBERON:0001965	97.38	gold quality
bronchial epithelial cell	CL:0002328	97.36	gold quality
inferior olivary complex	UBERON:0002127	97.31	gold quality
occipital lobe	UBERON:0002021	97.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.21	gold quality
medulla oblongata	UBERON:0001896	97.13	gold quality
primary visual cortex	UBERON:0002436	97.12	gold quality
pons	UBERON:0000988	97.10	gold quality
ventral tegmental area	UBERON:0002691	96.94	gold quality
parotid gland	UBERON:0001831	96.86	gold quality
prefrontal cortex	UBERON:0000451	96.83	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-53	no	134.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, MYF5, MYOD1, RFXANK

miRNA regulators (miRDB)

148 targeting ATP9A, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-450B-5P	99.92	71.48	3175

Literature-anchored findings (GeneRIF, showing 8)

• the predominant P4 ATPases in pure pancreatic beta cells and human and rat pancreatic islets were ATP8B1, ATP8B2, and ATP9A. ATP8B1 and CDC50A were highly concentrated in ISG (PMID:26240149)
• an evolutionary conserved MON2:DOPEY2:ATP9A complex is required for SNX3 retromer mediation of Wntless sorting and Wnt secretion (PMID:30213940)
• Pharmacological blocking of exosome release in ATP9A knockdown cells did significantly reduce the total number of Extracellular vesicles . Our data support a role for ATP9A in the regulation of exosome release from human cells. (PMID:30947313)
• Effects of ATP9A on Extracellular Vesicle Release and Exosomal Lipid Composition. (PMID:33178388)
• Biallelic truncating variants in ATP9A cause a novel neurodevelopmental disorder involving postnatal microcephaly and failure to thrive. (PMID:34379057)
• Structural basis of the P4B ATPase lipid flippase activity. (PMID:34645814)
• The phospholipid flippase ATP9A enhances macropinocytosis to promote nutrient starvation tolerance in hepatocellular carcinoma. (PMID:36715683)
• Circular RNA circATP9A promotes non-small cell lung cancer progression by interacting with HuR and by promoting extracellular vesicles-mediated macrophage M2 polarization. (PMID:38049814)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ATP9A	ENSDARG00000115869
mus_musculus	Atp9a	ENSMUSG00000027546
rattus_norvegicus	Atp9a	ENSRNOG00000049484
drosophila_melanogaster	CG9981	FBGN0030746
drosophila_melanogaster	CG4301	FBGN0030747
drosophila_melanogaster	CG31729	FBGN0051729
caenorhabditis_elegans	tat-5	WBGENE00009498
caenorhabditis_elegans		WBGENE00017174

Paralogs (13): ATP11B (ENSG00000058063), ATP11A (ENSG00000068650), ATP8B1 (ENSG00000081923), ATP11C (ENSG00000101974), ATP8B4 (ENSG00000104043), ATP10B (ENSG00000118322), ATP8A1 (ENSG00000124406), ATP8B3 (ENSG00000130270), ATP8A2 (ENSG00000132932), ATP8B2 (ENSG00000143515), ATP10D (ENSG00000145246), ATP9B (ENSG00000166377), ATP10A (ENSG00000206190)

Protein

Protein identifiers

Probable phospholipid-transporting ATPase IIA — O75110 (reviewed: O75110)

Alternative names: ATPase class II type 9A

All UniProt accessions (2): A0A0A0MR22, O75110

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in regulating membrane trafficking of cargo proteins, namely endosome to plasma membrane recycling, probably acting through RAB5 and RAB11 activation. Also involved in endosome to trans-Golgi network retrograde transport. In complex with MON2 and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS, a transporter of Wnt morphogens in developing tissues. Participates in the formation of endosomal carriers that direct WLS trafficking back to Golgi, away from lysosomal degradation. Appears to be implicated in intercellular communication by negatively regulating the release of exosomes. The flippase activity towards membrane lipids and its role in membrane asymmetry remains to be proved. Required for the maintenance of neurite morphology and synaptic transmission.

Subunit / interactions. Heterotrimer with MON2 and DOP1B; this complex regulates SNX3-retromer mediated endosomal sorting of WLS. Interacts with RAB5A and RAB11A.

Subcellular location. Early endosome membrane. Recycling endosome membrane. Late endosome membrane. Golgi apparatus. trans-Golgi network membrane. Cell membrane.

Disease relevance. Neurodevelopmental disorder with poor growth and behavioral abnormalities (NEDGBA) [MIM:620242] An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, absent speech, and behavioral abnormalities, including hyperactivity and attention deficit disorder. Affected individuals show failure to thrive with poor overall growth, and some have microcephaly. Additional features may include non-specific facial dysmorphism, hypotonia, and feeding difficulties. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O75110-1	Long	yes
O75110-2	Short

RefSeq proteins (1): NP_006036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001757	P_typ_ATPase	Family
IPR006539	P-type_ATPase_IV	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
IPR032630	P_typ_ATPase_c	Domain
IPR032631	P-type_ATPase_N	Domain
IPR036412	HAD-like_sf	Homologous_superfamily
IPR044492	P_typ_ATPase_HD_dom	Domain
IPR059000	ATPase_P-type_domA	Domain

Pfam: PF00122, PF00702, PF16209, PF16212

Enzyme classification (BRENDA):

• EC 7.6.2.1 — P-type phospholipid transporter (BRENDA: 22 organisms, 260 substrates, 62 inhibitors, 53 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.016–2.215	41
P-NITROPHENYL PHOSPHATE	1.17–1.46	3
ACETYL PHOSPHATE	1.03–1.31	2
1-PALMITOYL-2-OLEOYL-SN-GLYCERO-3-PHOSPHO-L-SERI	0.111	1

UniProt features (52 total): binding site 19, topological domain 11, transmembrane region 10, sequence variant 4, sequence conflict 3, initiator methionine 1, chain 1, active site 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9VDK	ELECTRON MICROSCOPY	2.18
9VDL	ELECTRON MICROSCOPY	2.31
9VDN	ELECTRON MICROSCOPY	2.61
9VDM	ELECTRON MICROSCOPY	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75110-F1	84.28	0.41

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): 391 (4-aspartylphosphate intermediate)

Ligand- & substrate-binding residues (19): 391; 391; 392; 393; 393; 502; 544; 549; 568; 597; 677; 678 …

Post-translational modifications (1): 2

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: 314 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GNF2_RTN1, GOBP_VESICLE_LOCALIZATION, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, MODULE_66, GOBP_EXOCYTOSIS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (10): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), endocytosis (GO:0006897), phospholipid translocation (GO:0045332), neuron projection morphogenesis (GO:0048812), negative regulation of exosomal secretion (GO:1903542), regulation of retrograde transport, endosome to Golgi (GO:1905279), regulation of endocytic recycling (GO:2001135), lipid transport (GO:0006869), phospholipid transport (GO:0015914), lipid translocation (GO:0034204)

GO Molecular Function (9): magnesium ion binding (GO:0000287), protease binding (GO:0002020), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ATPase-coupled intramembrane lipid carrier activity (GO:0140326), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (13): endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), trans-Golgi network membrane (GO:0032588), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), Golgi apparatus (GO:0005794), 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
endosome	3
endosome membrane	3
regulation of intracellular transport	2
regulation of vesicle-mediated transport	2
lipid transport	2
ATP-dependent activity	2
endomembrane system	2
cytoplasm	2
cellular anatomical structure	2
Golgi vesicle transport	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
phospholipid transport	1
lipid translocation	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
negative regulation of exocytosis	1
regulation of exosomal secretion	1
exosomal secretion	1
retrograde transport, endosome to Golgi	1
endocytic recycling	1
transport	1
lipid localization	1
organophosphate ester transport	1
regulation of membrane lipid distribution	1
metal ion binding	1
enzyme binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
intramembrane lipid carrier activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
cation binding	1
cytoplasmic vesicle	1
Golgi apparatus subcompartment	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP9A	CDC50A	Q9NV96	660
ATP9A	CDC50B	Q3MIR4	642
ATP9A	NEO1	Q92859	527
ATP9A	MYO1G	B0I1T2	526
ATP9A	MON2	Q7Z3U7	513
ATP9A	DOP1A	Q5JWR5	504
ATP9A	EFHC1	Q5JVL4	480
ATP9A	TRAPPC2L	Q9UL33	461
ATP9A	MICAL3	Q7RTP6	453
ATP9A	MOB4	Q9Y3A3	416
ATP9A	FRMD4A	Q9P2Q2	416
ATP9A	DOP1B	Q9Y3R5	406
ATP9A	MICOS10	Q5TGZ0	395
ATP9A	KLF13	Q9Y2Y9	391
ATP9A	SNX3	O60493	372

IntAct

121 interactions, top by confidence:

A	B	Type	Score
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
TMED2	ATP9A	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
RETREG3	PLSCR1	psi-mi:“MI:0914”(association)	0.640
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
SCN3B	ABCC5	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC1A5	GPR89A	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
SYP	APBB1	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
RIC3	ATP9A	psi-mi:“MI:0914”(association)	0.530

BioGRID (127): ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ABCC3 (Co-fractionation), ACADM (Co-fractionation), ATP2B4 (Co-fractionation), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (Affinity Capture-MS), ATP9A (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: A1A4J6, A3FIN4, D4ABB8, F1Q4S1, G2X7W6, G5EBH1, O43861, O70228, O75110, O94296, P05025, P13607, P25489, P35317, P39524, P40527, P57792, P70704, P98195, P98196, P98197, P98198, P98199, P98205, Q10309, Q29449, Q6DFW5, Q6RWA9, Q8TF62, Q92123, Q9GKS6, Q9LK90, Q9N0Z4, Q9NTI2, Q9Y2G3, Q9Y2Q0, Q9YH26, S7VVK4, C7EXK4, P98200

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATP9A	“form complex”	“ATP9A-DOP1B-MON2, golgi transporter complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class A/1 (Rhodopsin-like receptors)	13	10.8×	8e-08
Chemokine receptors bind chemokines	5	10.5×	9e-03
GPCR ligand binding	10	7.2×	3e-04
Signaling by GPCR	11	5.0×	2e-03
GPCR downstream signalling	10	4.9×	4e-03
G alpha (i) signalling events	11	4.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	15	14.2×	1e-10
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	8	14.1×	4e-05
calcium-mediated signaling	7	10.3×	1e-03
cell chemotaxis	6	9.0×	7e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	8	7.3×	2e-03
G protein-coupled receptor signaling pathway	14	4.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	5
Uncertain significance	114
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1284890	NM_006045.3(ATP9A):c.327+1G>T	Pathogenic
1284891	NM_006045.3(ATP9A):c.799+1G>T	Pathogenic
1706531	NM_006045.3(ATP9A):c.868C>T (p.Arg290Ter)	Pathogenic
2443772	NM_006045.3(ATP9A):c.642+1G>A	Pathogenic
2443774	NM_006045.3(ATP9A):c.433C>T (p.Arg145Ter)	Pathogenic
2443775	NM_006045.3(ATP9A):c.658C>T (p.Arg220Ter)	Pathogenic
2443776	NM_006045.3(ATP9A):c.983G>A (p.Trp328Ter)	Pathogenic
3327	NC_000020.11:g.(51758515_51770114)(51894383?)del	Pathogenic
3910011	NM_006045.3(ATP9A):c.2701G>T (p.Glu901Ter)	Pathogenic
2690551	NM_006045.3(ATP9A):c.1164dup (p.Leu389fs)	Likely pathogenic
3384062	NM_006045.3(ATP9A):c.2031_2032del (p.Asp679fs)	Likely pathogenic
3384063	NM_006045.3(ATP9A):c.1777C>T (p.Arg593Ter)	Likely pathogenic
4081196	NM_006045.3(ATP9A):c.307dup (p.Tyr103fs)	Likely pathogenic
4846929	NM_006045.3(ATP9A):c.1181-2A>G	Likely pathogenic

SpliceAI

4956 predictions. Top by Δscore:

Variant	Effect	Δscore
20:51601264:TGAGG:T	donor_gain	1.0000
20:51604810:GTCTT:G	donor_loss	1.0000
20:51604811:TCTTA:T	donor_loss	1.0000
20:51604812:CTTA:C	donor_loss	1.0000
20:51604813:TTA:T	donor_loss	1.0000
20:51604814:TACC:T	donor_loss	1.0000
20:51604815:A:AC	donor_gain	1.0000
20:51604816:C:CA	donor_loss	1.0000
20:51604816:C:CC	donor_gain	1.0000
20:51604816:CCG:C	donor_gain	1.0000
20:51605017:CTCC:C	acceptor_gain	1.0000
20:51605018:TCC:T	acceptor_gain	1.0000
20:51605019:CC:C	acceptor_gain	1.0000
20:51605019:CCC:C	acceptor_gain	1.0000
20:51605019:CCCT:C	acceptor_loss	1.0000
20:51605020:CC:C	acceptor_gain	1.0000
20:51605020:CCTG:C	acceptor_loss	1.0000
20:51605021:C:CC	acceptor_gain	1.0000
20:51605021:CTGCA:C	acceptor_loss	1.0000
20:51605022:T:C	acceptor_loss	1.0000
20:51607521:CCTTA:C	donor_loss	1.0000
20:51607522:CTTAC:C	donor_loss	1.0000
20:51607523:TTACC:T	donor_loss	1.0000
20:51607524:TACC:T	donor_loss	1.0000
20:51607525:A:C	donor_loss	1.0000
20:51608528:T:TA	donor_gain	1.0000
20:51608587:C:CT	acceptor_gain	1.0000
20:51608588:A:T	acceptor_gain	1.0000
20:51613672:CTCA:C	donor_loss	1.0000
20:51613674:CACCT:C	donor_loss	1.0000

AlphaMissense

6824 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:51604863:G:C	S987R	1.000
20:51604863:G:T	S987R	1.000
20:51604865:T:G	S987R	1.000
20:51607537:G:C	S931R	1.000
20:51607537:G:T	S931R	1.000
20:51607539:T:G	S931R	1.000
20:51619012:A:G	L716P	1.000
20:51622169:A:G	W674R	1.000
20:51622169:A:T	W674R	1.000
20:51601286:G:C	S1023R	0.999
20:51601286:G:T	S1023R	0.999
20:51601288:T:G	S1023R	0.999
20:51604927:A:G	L966P	0.999
20:51604942:A:G	L961P	0.999
20:51607527:C:A	G935W	0.999
20:51607527:C:G	G935R	0.999
20:51607527:C:T	G935R	0.999
20:51610157:A:C	F860L	0.999
20:51610157:A:T	F860L	0.999
20:51610159:A:G	F860L	0.999
20:51613686:G:C	S854R	0.999
20:51613686:G:T	S854R	0.999
20:51613688:T:G	S854R	0.999
20:51613702:C:A	R849M	0.999
20:51613723:A:G	L842P	0.999
20:51613750:C:G	R833P	0.999
20:51613753:C:A	G832V	0.999
20:51613753:C:T	G832D	0.999
20:51613754:C:G	G832R	0.999
20:51617538:G:C	D789E	0.999

dbSNP variants (sampled 300 via entrez): RS1000009857 (20:51602181 G>A), RS1000013858 (20:51640669 C>T), RS1000032733 (20:51678034 A>G), RS1000051905 (20:51751046 C>G,T), RS1000059804 (20:51684162 G>A), RS1000062794 (20:51759337 T>A), RS1000063804 (20:51596222 C>G,T), RS1000086394 (20:51642330 A>T), RS1000095130 (20:51715465 G>A), RS1000121501 (20:51601954 C>G,T), RS1000123320 (20:51603092 C>T), RS1000128085 (20:51640993 C>A,G,T), RS1000130004 (20:51678680 C>T), RS1000137601 (20:51606971 T>C), RS1000165590 (20:51683606 G>A)

Disease associations

OMIM: gene MIM:609126 | disease phenotypes: MIM:620242, MIM:607323

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with poor growth and behavioral abnormalities	Strong	Autosomal recessive

Mondo (2): neurodevelopmental disorder with poor growth and behavioral abnormalities (MONDO:0859377), Duane-radial ray syndrome (MONDO:0011812)

Orphanet (2): Okihiro syndrome (Orphanet:93293), Acro-renal-ocular syndrome (Orphanet:959)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000286	Epicanthus
HP:0000319	Smooth philtrum
HP:0000486	Strabismus
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001270	Motor delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001324	Muscle weakness
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001684	Secundum atrial septal defect
HP:0002017	Nausea and vomiting
HP:0002020	Gastroesophageal reflux
HP:0002079	Hypoplasia of the corpus callosum
HP:0002188	Delayed CNS myelination
HP:0002311	Incoordination
HP:0002360	Sleep disturbance
HP:0003577	Congenital onset
HP:0003593	Infantile onset

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002682_15	Tourette’s syndrome or obsessive-compulsive disorder	8.000000e-06
GCST009391_1337	Metabolite levels	3.000000e-06
GCST009391_1403	Metabolite levels	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010362	lysophosphatidylcholine 20:3 measurement
EFO:0005132	5-HIAA 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 — P4 P-type ATPases: Phospholipid-transporting ATPases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
Benzo(a)pyrene	affects methylation, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Particulate Matter	increases abundance, increases expression, affects cotreatment	3
bisphenol A	decreases expression, increases expression, increases methylation	2
Panobinostat	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression, decreases methylation	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
nickel sulfate	increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
licochalcone B	decreases expression	1
bisphenol AF	increases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Glyphosate	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SE21	HAP1 ATP9A (-) 1	Cancer cell line	Male
CVCL_XL78	HAP1 ATP9A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies