ATP11A

Summary

ATP11A (ATPase phospholipid transporting 11A, HGNC:13552) is a protein-coding gene on chromosome 13q34, encoding Phospholipid-transporting ATPase IH (P98196). Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane.

The protein encoded by this gene is an integral membrane ATPase. The encoded protein is probably phosphorylated in its intermediate state and likely drives the transport of ions such as calcium across membranes.

Source: NCBI Gene 23250 — RefSeq curated summary.

At a glance

• Gene–disease (curated): auditory neuropathy, autosomal dominant 2 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 28
• Clinical variants (ClinVar): 311 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 47
• MANE Select transcript: NM_015205

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13552
Approved symbol	ATP11A
Name	ATPase phospholipid transporting 11A
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	ATPIH, ATPIS, KIAA1021
Ensembl gene	ENSG00000068650
Ensembl biotype	protein_coding
OMIM	605868
Entrez	23250

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 5 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000375630, ENST00000375645, ENST00000415301, ENST00000418678, ENST00000419448, ENST00000419631, ENST00000459011, ENST00000459908, ENST00000466946, ENST00000471555, ENST00000479193, ENST00000487903, ENST00000489577, ENST00000493489, ENST00000495930, ENST00000610419, ENST00000614170, ENST00000905214, ENST00000953141

RefSeq mRNA: 5 — MANE Select: NM_015205 NM_001405661, NM_001405662, NM_001405663, NM_015205, NM_032189

CCDS: CCDS32011

Canonical transcript exons

ENST00000375645 — 30 exons

Exon	Start	End
ENSE00000687268	112860287	112860414
ENSE00000862484	112857818	112857920
ENSE00000862485	112858145	112858290
ENSE00001467710	112881876	112887168
ENSE00001769760	112859393	112859452
ENSE00003459752	112851037	112851218
ENSE00003466979	112871735	112871800
ENSE00003471332	112785135	112785257
ENSE00003478041	112873573	112873676
ENSE00003484183	112823345	112823409
ENSE00003496443	112804957	112805046
ENSE00003496999	112824344	112824425
ENSE00003540345	112816083	112816211
ENSE00003558741	112826694	112826891
ENSE00003559934	112819900	112819950
ENSE00003568313	112878217	112878303
ENSE00003574834	112855911	112856085
ENSE00003592659	112806213	112806293
ENSE00003610890	112875776	112875941
ENSE00003613558	112819304	112819407
ENSE00003624959	112854279	112854530
ENSE00003635655	112862440	112862575
ENSE00003645419	112834589	112834660
ENSE00003647508	112842276	112842379
ENSE00003654681	112825430	112825580
ENSE00003660380	112836178	112836251
ENSE00003674225	112831375	112831548
ENSE00003676612	112832860	112833023
ENSE00003681393	112810619	112810726
ENSE00003920126	112690038	112690455

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8079 / max 639.6168, expressed in 1791 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136154	8.2443	1732
136149	2.9534	1141
136153	2.0014	1130
136150	1.9786	833
136152	1.9466	1141
136151	1.4909	999
136155	0.7472	469
136157	0.1701	33
136158	0.1428	24
136160	0.0523	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.54	gold quality
visceral pleura	UBERON:0002401	99.33	gold quality
heart right ventricle	UBERON:0002080	97.26	gold quality
lower lobe of lung	UBERON:0008949	97.17	gold quality
parietal pleura	UBERON:0002400	97.07	gold quality
pleura	UBERON:0000977	96.05	gold quality
inferior vagus X ganglion	UBERON:0005363	95.23	gold quality
amniotic fluid	UBERON:0000173	95.02	gold quality
subthalamic nucleus	UBERON:0001906	94.63	gold quality
upper lobe of lung	UBERON:0008948	94.38	gold quality
upper lobe of left lung	UBERON:0008952	94.12	gold quality
dorsal root ganglion	UBERON:0000044	94.10	gold quality
corpus callosum	UBERON:0002336	93.78	gold quality
adult organism	UBERON:0007023	93.64	gold quality
lateral globus pallidus	UBERON:0002476	93.36	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.17	gold quality
monocyte	CL:0000576	92.75	gold quality
right lung	UBERON:0002167	92.64	gold quality
pigmented layer of retina	UBERON:0001782	92.58	gold quality
jejunal mucosa	UBERON:0000399	92.55	gold quality
jejunum	UBERON:0002115	92.53	gold quality
sural nerve	UBERON:0015488	92.42	gold quality
mononuclear cell	CL:0000842	92.36	gold quality
trigeminal ganglion	UBERON:0001675	92.02	gold quality
renal medulla	UBERON:0000362	91.94	gold quality
lung	UBERON:0002048	91.91	gold quality
leukocyte	CL:0000738	91.90	gold quality
secondary oocyte	CL:0000655	91.39	gold quality
trabecular bone tissue	UBERON:0002483	91.31	gold quality
endometrium	UBERON:0001295	91.25	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	597.05
E-MTAB-8221	yes	533.10
E-ANND-3	yes	23.93
E-GEOD-130148	yes	9.51
E-GEOD-124858	no	63.00
E-MTAB-6678	no	3.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

247 targeting ATP11A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-19B-3P	99.98	75.44	2754

Literature-anchored findings (GeneRIF, showing 8)

• ATP11A is a useful predictive marker of metastasis in colorectal cancer patients. (PMID:20043114)
• The lipid flippases, ATP8B1 and ATP11A are novel elements of the innate immune response that are essential to attenuate the inflammatory response, possibly by mediating endotoxin-induced internalization of TLR4. (PMID:27628304)
• Disease Mutation Study Identifies Critical Residues for Phosphatidylserine Flippase ATP11A. (PMID:32596364)
• DNA Methylation at ATP11A cg11702988 Is a Biomarker of Lung Disease Severity in Cystic Fibrosis: A Longitudinal Study. (PMID:33808877)
• A sublethal ATP11A mutation associated with neurological deterioration causes aberrant phosphatidylcholine flipping in plasma membranes. (PMID:34403372)
• Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene. (PMID:35278131)
• A mutation in ATP11A causes autosomal-dominant auditory neuropathy type 2. (PMID:36300302)
• Association of a Single Nucleotide Variant in TERT with Airway Disease in Japanese Rheumatoid Arthritis Patients. (PMID:38003027)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp11a	ENSDARG00000008413
mus_musculus	Atp11a	ENSMUSG00000031441
rattus_norvegicus	Atp11a	ENSRNOG00000017154
drosophila_melanogaster	CG9981	FBGN0030746
drosophila_melanogaster	CG4301	FBGN0030747
drosophila_melanogaster	CG31729	FBGN0051729
caenorhabditis_elegans	tat-5	WBGENE00009498
caenorhabditis_elegans		WBGENE00017174

Paralogs (13): ATP9A (ENSG00000054793), ATP11B (ENSG00000058063), 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

Phospholipid-transporting ATPase IH — P98196 (reviewed: P98196)

Alternative names: ATPase IS, ATPase class VI type 11A, P4-ATPase flippase complex alpha subunit ATP11A

All UniProt accessions (7): P98196, A0A087WVE8, A2A3G9, E9PEJ6, H0Y547, H0Y624, H0Y8F0

UniProt curated annotations — full annotation on UniProt →

Function. Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane. Does not show flippase activity toward phosphatidylcholine (PC). Contributes to the maintenance of membrane lipid asymmetry with a specific role in morphogenesis of muscle cells. In myoblasts, mediates PS enrichment at the inner leaflet of plasma membrane, triggering PIEZO1-dependent Ca2+ influx and Rho GTPases signal transduction, subsequently leading to the assembly of cortical actomyosin fibers and myotube formation. May be involved in the uptake of farnesyltransferase inhibitor drugs, such as lonafarnib.

Subunit / interactions. Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP11A and an accessory beta subunit TMEM30A.

Subcellular location. Cell membrane. Early endosome. Recycling endosome. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. Expressed in myoblasts.

Post-translational modifications. Proteolytically cleaved by CASP3.

Disease relevance. Deafness, autosomal dominant, 84 (DFNA84) [MIM:619810] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA84 is characterized by slowly progressive, postlingual hearing loss. The disease is caused by variants affecting the gene represented in this entry. Leukodystrophy, hypomyelinating, 24 (HLD24) [MIM:619851] An autosomal dominant disorder characterized by global developmental delay apparent in infancy, impaired intellectual development, and loss of developmental milestones and ambulation. Brain imaging shows non-progressive severe cerebral atrophy, ventriculomegaly, hypomyelinating leukodystrophy, and thinning of the corpus callosum. The disease is caused by variants affecting the gene represented in this entry. Auditory neuropathy, autosomal dominant 2 (AUNA2) [MIM:620384] A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. Affected individuals typically respond to sound but have difficulties in speech discrimination. AUNA2 is characterized by postlingual onset of progressive bilateral sensorineural hearing loss in the second decade, leading to profound deafness in the fifth decade. The outer hair cell function is preserved initially but declines with age. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. The flippase activity is inactivated by caspase-mediated cleavage in apoptotic cells, allowing for PS exposure on the cell surface and engulfment of apoptotic cells by macrophages. The ATPase activity is up-regulated by aminophospholipids PS and PE and down-regulated by increasing intracellular Ca2+ levels.

Miscellaneous. Overexpression of ATP11A confers resistance to lonafarnib.

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

RefSeq proteins (5): NP_001392590, NP_001392591, NP_001392592, NP_056020, NP_115565 (=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, PF13246, 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

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) + ADP + phosphate + H(+) (RHEA:38567)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) + ATP + H2O = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) + ADP + phosphate + H(+) (RHEA:66132)

UniProt features (56 total): binding site 18, topological domain 11, transmembrane region 10, mutagenesis site 9, sequence variant 3, site 2, chain 1, active site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98196-F1	83.48	0.40

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 (3): 414 (4-aspartylphosphate intermediate); 457–458 (cleavage; by casp3); 490–491 (cleavage; by casp3)

Ligand- & substrate-binding residues (18): 414; 414; 415; 416; 416; 511; 553; 576; 607; 687; 688; 689 …

Post-translational modifications (1): 738

Mutagenesis-validated functional residues (9):

Position	Phenotype
84	does not affect flippase activity toward phosphatidylserine. like the wild type, it is unable to translocate phosphatidy
186	has no effect on endoplasmic reticulum to plasma membrane trafficking. impairs flippase activity toward phosphatidylseri
414	impairs endoplasmic reticulum to plasma membrane trafficking.
454	impairs caspase-mediated cleavage; when associated with a-457, a-487 and a-490.
457	impairs caspase-mediated cleavage; when associated with a-454, a-487 and a-490.
487	impairs caspase-mediated cleavage; when associated with a-454, a-457 and a-490.
490	impairs caspase-mediated cleavage; when associated with a-454, a-457 and a-487.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-382551	Transport of small molecules
R-HSA-983712	Ion channel transport

MSigDB gene sets: 384 (showing top): GOBP_POSITIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, PEREZ_TP63_TARGETS, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, MODULE_16, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, BOYLAN_MULTIPLE_MYELOMA_D_DN, DOANE_BREAST_CANCER_CLASSES_DN

GO Biological Process (7): positive regulation of myotube differentiation (GO:0010831), phospholipid translocation (GO:0045332), regulation of membrane lipid distribution (GO:0097035), lipid transport (GO:0006869), phospholipid transport (GO:0015914), lipid translocation (GO:0034204), aminophospholipid translocation (GO:0140331)

GO Molecular Function (11): magnesium ion binding (GO:0000287), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), phosphatidylethanolamine flippase activity (GO:0090555), phosphatidylserine floppase activity (GO:0090556), ATPase-coupled intramembrane lipid carrier activity (GO:0140326), phosphatidylserine flippase activity (GO:0140346), nucleotide binding (GO:0000166), transporter activity (GO:0005215), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (13): lysosomal membrane (GO:0005765), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), specific granule membrane (GO:0035579), recycling endosome (GO:0055037), tertiary granule membrane (GO:0070821), phospholipid-translocating ATPase complex (GO:1990531), endosome (GO:0005768), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Innate Immune System	1
Ion channel transport	1
Immune System	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
lipid transport	2
ATP-dependent activity	2
glycerophospholipid flippase activity	2
endosome	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
secretory granule membrane	2
regulation of myotube differentiation	1
myotube differentiation	1
positive regulation of striated muscle cell differentiation	1
phospholipid transport	1
lipid translocation	1
membrane organization	1
regulation of biological quality	1
transport	1
lipid localization	1
organophosphate ester transport	1
regulation of membrane lipid distribution	1
aminophospholipid transport	1
phospholipid translocation	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
floppase activity	1
intramembrane lipid carrier activity	1
aminophospholipid flippase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
binding	1
cation binding	1
lysosome	1
lytic vacuole membrane	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1

Protein interactions and networks

STRING

1444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP11A	CDC50A	Q9NV96	794
ATP11A	XKR8	Q9H6D3	672
ATP11A	CTNNA3	Q9UI47	598
ATP11A	FAM13A	O94988	574
ATP11A	DPP9	Q86TI2	571
ATP11A	SPPL2C	Q8IUH8	544
ATP11A	TUBGCP3	Q96CW5	514
ATP11A	KLHL8	Q9P2G9	510
ATP11A	FHAD1	B1AJZ9	507
ATP11A	STN1	Q9H668	505
ATP11A	DSTYK	Q6XUX3	490
ATP11A	CDC50B	Q3MIR4	490
ATP11A	XKR9	Q5GH70	443
ATP11A	MUC5B	Q9HC84	442
ATP11A	MAD1L1	Q9Y6D9	419
ATP11A	ANO6	Q4KMQ2	419

IntAct

18 interactions, top by confidence:

A	B	Type	Score
TMEM30A	ATP11A	psi-mi:“MI:0915”(physical association)	0.800
ATP11A	TMEM30A	psi-mi:“MI:0915”(physical association)	0.800
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
RAB11A	SCAMP1	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	SDCBP	psi-mi:“MI:0914”(association)	0.350
ATP11A	ATP11C	psi-mi:“MI:0914”(association)	0.350
PIGH	ILVBL	psi-mi:“MI:0914”(association)	0.350
LGALS3	SDCBP	psi-mi:“MI:0914”(association)	0.350
SLC16A10	STXBP3	psi-mi:“MI:0914”(association)	0.350
SLC2A1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): ATP11A (Affinity Capture-MS), ATP11A (Affinity Capture-MS), ATP11A (Affinity Capture-MS), ATP11A (Affinity Capture-MS), ATP11A (Affinity Capture-RNA), ATP11A (Affinity Capture-RNA), ATP11A (Proximity Label-MS), ATP11A (Proximity Label-MS), ATP11A (Affinity Capture-RNA), ATP11A (Affinity Capture-MS), ATP11A (Proximity Label-MS), ATP11A (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), OMA1 (Affinity Capture-MS), RCOR3 (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, B1AWN4, C7EXK4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	209
Likely benign	40
Benign	17

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1327581	NM_015205.3(ATP11A):c.3322_3327+2dup	Pathogenic
1527862	NM_015205.3(ATP11A):c.11G>A (p.Ser4Asn)	Pathogenic
1686851	NM_015205.3(ATP11A):c.250C>G (p.Gln84Glu)	Pathogenic
4684988	NM_015205.3(ATP11A):c.334-8T>G	Pathogenic
2444276	NM_015205.3(ATP11A):c.3044_3045del (p.Thr1015fs)	Likely pathogenic

SpliceAI

7498 predictions. Top by Δscore:

Variant	Effect	Δscore
13:112690452:ATAC:A	donor_gain	1.0000
13:112690453:TAC:T	donor_gain	1.0000
13:112690456:G:GG	donor_gain	1.0000
13:112785133:A:AG	acceptor_gain	1.0000
13:112785133:AGT:A	acceptor_gain	1.0000
13:112785134:G:GT	acceptor_gain	1.0000
13:112785134:GT:G	acceptor_gain	1.0000
13:112785134:GTG:G	acceptor_gain	1.0000
13:112785134:GTGT:G	acceptor_gain	1.0000
13:112785253:CCAAG:C	donor_loss	1.0000
13:112785254:CAAG:C	donor_loss	1.0000
13:112785255:AAGGT:A	donor_loss	1.0000
13:112785256:AGGT:A	donor_loss	1.0000
13:112785257:GGT:G	donor_loss	1.0000
13:112785258:G:GC	donor_loss	1.0000
13:112785259:T:A	donor_loss	1.0000
13:112806211:A:AG	acceptor_gain	1.0000
13:112806211:AGTT:A	acceptor_gain	1.0000
13:112806212:G:GC	acceptor_gain	1.0000
13:112806212:GT:G	acceptor_gain	1.0000
13:112806212:GTT:G	acceptor_gain	1.0000
13:112806212:GTTG:G	acceptor_gain	1.0000
13:112806291:CAGG:C	donor_loss	1.0000
13:112806293:GGTA:G	donor_loss	1.0000
13:112806294:G:T	donor_loss	1.0000
13:112806295:T:A	donor_loss	1.0000
13:112810727:G:GG	donor_gain	1.0000
13:112816077:CTGTA:C	acceptor_loss	1.0000
13:112816078:TGTA:T	acceptor_loss	1.0000
13:112816079:GTA:G	acceptor_loss	1.0000

AlphaMissense

7490 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:112805016:C:A	N74K	1.000
13:112805016:C:G	N74K	1.000
13:112805023:T:C	F77L	1.000
13:112805025:C:A	F77L	1.000
13:112805025:C:G	F77L	1.000
13:112806246:A:C	S96R	1.000
13:112806248:C:A	S96R	1.000
13:112806248:C:G	S96R	1.000
13:112806282:G:C	A108P	1.000
13:112826752:C:A	P361H	1.000
13:112826752:C:G	P361R	1.000
13:112831393:G:C	D414H	1.000
13:112831394:A:C	D414A	1.000
13:112831394:A:T	D414V	1.000
13:112836203:T:C	F553L	1.000
13:112836205:T:A	F553L	1.000
13:112836205:T:G	F553L	1.000
13:112851214:G:C	D663H	1.000
13:112851215:A:C	D663A	1.000
13:112854337:T:A	W684R	1.000
13:112854337:T:C	W684R	1.000
13:112856077:A:C	K804Q	1.000
13:112857883:T:A	N828K	1.000
13:112857883:T:G	N828K	1.000
13:112857885:A:C	D829A	1.000
13:112857885:A:T	D829V	1.000
13:112860322:C:A	N921K	1.000
13:112860322:C:G	N921K	1.000
13:112805007:A:C	R71S	0.999
13:112805007:A:T	R71S	0.999

dbSNP variants (sampled 300 via entrez): RS1000003516 (13:112775636 A>G), RS1000010128 (13:112827189 C>CT), RS1000011278 (13:112874033 A>G), RS1000051739 (13:112717961 C>T), RS1000068379 (13:112880016 T>A,C), RS1000082690 (13:112753388 G>A), RS1000082849 (13:112839800 A>G), RS1000090942 (13:112711538 C>A,T), RS1000130936 (13:112725563 C>G,T), RS1000139792 (13:112808145 G>C), RS1000161291 (13:112693111 G>C), RS1000183896 (13:112747243 T>G), RS1000183980 (13:112725851 G>A), RS1000184776 (13:112705597 C>T), RS1000193205 (13:112827192 G>A)

Disease associations

OMIM: gene MIM:605868 | disease phenotypes: MIM:614211, MIM:619810, MIM:619851

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal dominant 84	Strong	Autosomal dominant
leukodystrophy, hypomyelinating, 24	Strong	Autosomal dominant
auditory neuropathy, autosomal dominant 2	Strong	Autosomal dominant
complex neurodevelopmental disorder	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss	Moderate	AD

Mondo (6): autosomal dominant nonsyndromic hearing loss 33 (MONDO:0013632), hearing loss, autosomal dominant 84 (MONDO:0030724), leukodystrophy, hypomyelinating, 24 (MONDO:0859242), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038), auditory neuropathy, autosomal dominant 2 (MONDO:0957279)

Orphanet (1): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000518	Cataract
HP:0000821	Hypothyroidism
HP:0001063	Acrocyanosis
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001284	Areflexia
HP:0001308	Tongue fasciculations
HP:0001371	Flexion contracture
HP:0001963	Abnormal speech discrimination
HP:0002020	Gastroesophageal reflux
HP:0002059	Cerebral atrophy
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002206	Pulmonary fibrosis
HP:0002376	Developmental regression
HP:0002415	Leukodystrophy
HP:0002875	Exertional dyspnea
HP:0003431	Decreased motor nerve conduction velocity
HP:0003477	Peripheral axonal neuropathy
HP:0003510	Severe short stature
HP:0003546	Exercise intolerance
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0003676	Progressive
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0010444	Pulmonic regurgitation
HP:0010976	Decreased total B cell count

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000803_11	Glycated hemoglobin levels	5.000000e-09
GCST001968_7	Interstitial lung disease	7.000000e-09
GCST004602_173	Mean corpuscular volume	6.000000e-10
GCST004619_146	Reticulocyte fraction of red cells	1.000000e-09
GCST004621_61	Red cell distribution width	4.000000e-28
GCST004621_62	Red cell distribution width	7.000000e-12
GCST006804_10	Red cell distribution width	2.000000e-09
GCST006804_97	Red cell distribution width	8.000000e-22
GCST007954_48	Glycated hemoglobin levels	2.000000e-12
GCST008870_34	Keratinocyte cancer (MTAG)	3.000000e-08
GCST008871_16	Basal cell carcinoma	2.000000e-09
GCST009758_8	Idiopathic pulmonary fibrosis	1.000000e-10
GCST010248_6	Machado-Joseph disease (age at onset)	4.000000e-06
GCST010303_32	Nevus count or cutaneous melanoma	2.000000e-08
GCST90002385_17	High light scatter reticulocyte count	4.000000e-10
GCST90002386_159	High light scatter reticulocyte percentage of red cells	1.000000e-12
GCST90002386_160	High light scatter reticulocyte percentage of red cells	2.000000e-10
GCST90002390_196	Mean corpuscular hemoglobin	1.000000e-20
GCST90002390_197	Mean corpuscular hemoglobin	8.000000e-11
GCST90002392_416	Mean corpuscular volume	4.000000e-21
GCST90002392_417	Mean corpuscular volume	2.000000e-12
GCST90002397_66	Mean spheric corpuscular volume	5.000000e-10
GCST90002403_497	Red blood cell count	2.000000e-14
GCST90002404_381	Red cell distribution width	5.000000e-81
GCST90002404_382	Red cell distribution width	1.000000e-29
GCST90002405_361	Reticulocyte count	2.000000e-12
GCST90002406_412	Reticulocyte fraction of red cells	4.000000e-17
GCST90002406_413	Reticulocyte fraction of red cells	2.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004541	HbA1c measurement
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0010176	keratinocyte carcinoma
EFO:0000768	idiopathic pulmonary fibrosis
EFO:0004847	age at onset
EFO:0004632	nevus count
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

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

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, affects methylation, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression	3
Estradiol	increases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	increases expression	3
Acetaminophen	decreases expression, increases expression	2
Ozone	affects expression, increases abundance, affects methylation	2
Particulate Matter	affects expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
cinnamaldehyde	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	affects methylation	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
mono-isobutyl phthalate	increases abundance, decreases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	decreases expression	1
Bucladesine	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases methylation, increases abundance	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism