CDC50A

Summary

CDC50A (cell division cycle 50 P4-ATPase accessory subunit A, HGNC:16667) is a protein-coding gene on chromosome 6q14.1, encoding Cell cycle control protein 50A (Q9NV96). Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids.

Enables aminophospholipid flippase activity and structural molecule activity. Involved in several processes, including phospholipid transport; positive regulation of transport; and xenobiotic transmembrane transport. Located in endoplasmic reticulum; endosome membrane; and plasma membrane. Part of phospholipid-translocating ATPase complex.

Source: NCBI Gene 55754 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_018247

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16667
Approved symbol	CDC50A
Name	cell division cycle 50 P4-ATPase accessory subunit A
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10856
Ensembl gene	ENSG00000112697
Ensembl biotype	protein_coding
OMIM	611028
Entrez	55754

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 nonsense_mediated_decay

ENST00000230461, ENST00000370050, ENST00000475111, ENST00000518161, ENST00000673730, ENST00000673989, ENST00000674038, ENST00000674104, ENST00000674151, ENST00000873066, ENST00000873067

RefSeq mRNA: 2 — MANE Select: NM_018247 NM_001143958, NM_018247

CCDS: CCDS47453, CCDS4983

Canonical transcript exons

ENST00000230461 — 7 exons

Exon	Start	End
ENSE00000758966	75258780	75258986
ENSE00001841269	75284402	75284792
ENSE00001903737	75252924	75256295
ENSE00002102850	75259347	75259490
ENSE00002122250	75260824	75260911
ENSE00003489079	75267641	75267748
ENSE00003490695	75265231	75265338

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 109.5079 / max 556.0877, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74465	105.7182	1824
74466	3.1224	1313
74463	0.4425	241
74464	0.2248	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.74	gold quality
trigeminal ganglion	UBERON:0001675	98.47	gold quality
superior vestibular nucleus	UBERON:0007227	98.38	gold quality
medial globus pallidus	UBERON:0002477	98.33	gold quality
dorsal root ganglion	UBERON:0000044	98.31	gold quality
endothelial cell	CL:0000115	98.26	gold quality
epithelium of nasopharynx	UBERON:0001951	98.21	gold quality
globus pallidus	UBERON:0001875	98.20	gold quality
inferior vagus X ganglion	UBERON:0005363	98.03	gold quality
stromal cell of endometrium	CL:0002255	98.02	gold quality
subthalamic nucleus	UBERON:0001906	98.02	gold quality
islet of Langerhans	UBERON:0000006	97.93	gold quality
substantia nigra pars compacta	UBERON:0001965	97.91	gold quality
type B pancreatic cell	CL:0000169	97.86	gold quality
ventral tegmental area	UBERON:0002691	97.84	gold quality
smooth muscle tissue	UBERON:0001135	97.76	gold quality
visceral pleura	UBERON:0002401	97.75	gold quality
seminal vesicle	UBERON:0000998	97.73	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.71	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.67	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.67	gold quality
descending thoracic aorta	UBERON:0002345	97.57	gold quality
pons	UBERON:0000988	97.50	gold quality
lateral globus pallidus	UBERON:0002476	97.50	gold quality
thoracic aorta	UBERON:0001515	97.25	gold quality
parietal pleura	UBERON:0002400	97.25	gold quality
pleura	UBERON:0000977	97.24	gold quality
cerebellar vermis	UBERON:0004720	97.22	gold quality
lower lobe of lung	UBERON:0008949	97.22	gold quality
ascending aorta	UBERON:0001496	97.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

136 targeting CDC50A, 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-4673	100.00	66.64	1490
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-5696	99.98	72.36	4487
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-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-512-3P	99.97	67.35	1049

Literature-anchored findings (GeneRIF, showing 16)

• CDC50A may be the potential beta-subunit or chaperone for ATP8B1 in hepatocytes. (PMID:17948906)
• CDC50A plays a key role in perifosine uptake in human cells, presumably by forming a functional plasma membrane translocator. (PMID:20510206)
• Import of choline phospholipids into Saccharomyces cerevisiae DeltaLem3 vector is partially reconstituted by human TMEM30a and by Lem3p-TMEM30a chimeras, showing that the proteins are orthologous. (PMID:21289302)
• CDC50A is the beta-subunit of ATP8A2 and is crucial for the correct folding, stable expression, export from endoplasmic reticulum, and phosphatidylserine flippase activity of ATP8A2 (PMID:21454556)
• the phospholipid flippase complex of ATP8A1 and CDC50A proteins has a role in cell migration (PMID:23269685)
• ATP11C and CDC50A are required for aminophospholipid translocation from the outer to the inner plasma membrane leaflet; that is, they display flippase activity. (PMID:24904167)
• Data indicate that the lipid flippase (ATP8B1)-transmembrane protein 30A (CDC50A) heterodimer is essential for the apical localization of sodium-dependent bile acid transporter (SLC10A2/ASBT) in Caco-2 cells. (PMID:25239307)
• results indicated that the extracellular domain of CDC50A has important roles both in CDC50A’s ability to chaperone ATP11C to the plasma membrane and in inducing ATP11C’s ATP hydrolysis-coupled flippase activity. (PMID:29276178)
• Identified TMEM30A as a candidate partner for beta-carboxyl-terminal fragment (betaCTF) of amyloid-beta precursor protein (APP). TMEM30A physically interacts with betaCTF in endosomes and may impair vesicular traffic, leading to abnormally enlarged endosomes. Data suggested that TMEM30A is involved in betaCTF-dependent endosome abnormalities that are related to Abeta overproduction. (PMID:30086173)
• Mechanistically, deletion of TMEM30A caused reduced endothelial cell proliferation by inhibiting VEGF-induced signaling. The findings reveal essential roles of TMEM30A in angiogenesis, providing a potential therapeutic target. (PMID:30814335)
• Highlights on a multifaceted role for TMEM30A in B-cell lymphomagenesis, and characterization of intrinsic and extrinsic vulnerabilities of cancer cells that can be therapeutically exploited. (PMID:32094924)
• Crystal structure of a human plasma membrane phospholipid flippase. (PMID:32493773)
• CircTMEM30A/hsa-miR-130a-3p regulates TNFalpha and promotes the malignant progression of COPD with primary lung cancer. (PMID:33616375)
• Loss of phosphatidylserine flippase beta-subunit Tmem30a in podocytes leads to albuminuria and glomerulosclerosis. (PMID:34080006)
• CDC50A is required for aminophospholipid transport and cell fusion in mouse C2C12 myoblasts. (PMID:34664668)
• Deletion of the TMEM30A gene enables leukemic cell evasion of NK cell cytotoxicity. (PMID:38557174)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem30aa	ENSDARG00000030236
danio_rerio	tmem30ab	ENSDARG00000043555
mus_musculus	Tmem30a	ENSMUSG00000032328
rattus_norvegicus	Tmem30a	ENSRNOG00000010895
drosophila_melanogaster	Cdc50	FBGN0030752
caenorhabditis_elegans		WBGENE00008969
caenorhabditis_elegans		WBGENE00012224
caenorhabditis_elegans		WBGENE00019946

Paralogs (1): TMEM30B (ENSG00000182107)

Protein

Protein identifiers

Cell cycle control protein 50A — Q9NV96 (reviewed: Q9NV96)

Alternative names: P4-ATPase flippase complex beta subunit TMEM30A, Transmembrane protein 30A

All UniProt accessions (6): Q9NV96, A0A669KB92, A0A669KBA0, A0A669KBE6, A0A669KBF5, E5RG19

UniProt curated annotations — full annotation on UniProt →

Function. Accessory component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth, and, reconstituted to liposomes, predomiminantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE). The ATP8A1:TMEM30A flippase complex seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the plasma membrane. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes. Involved in uptake of platelet-activating factor (PAF), synthetic drug alkylphospholipid edelfosine, and, probably in association with ATP8B1, of perifosine. Also mediates the export of alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C from the ER to other membrane localizations.

Subunit / interactions. Component of various P4-ATPase flippase complexes which consists of a catalytic alpha subunit and an accessory beta subunit. Interacts with ATP8A1 to form a flippase complex; this complex forms an intermediate phosphoenzyme. The ATP8A2:TMEM30A flippase complex has been purified, and ATP8B1:TMEM30A and ATP8B2:TMEM30A flippase complexes have been shown to form intermediate phosphoenzymes in vitro. Interacts with alpha subunits ATP8A1, ATP8B1, ATP8B2, ATP8B4, ATP10A, ATP10B, ATP10D, ATP11A, ATP11B and ATP11C.

Subcellular location. Membrane. Cell membrane. Golgi apparatus. Cytoplasmic vesicle. Secretory vesicle membrane. Apical cell membrane.

Post-translational modifications. N-glycosylated. Contains high mannose-type oligosaccharides.

Domain organisation. The N-terminal domain seems to play a role in the reaction cycle of the catalytic subunit such as ATP8A2.

Similarity. Belongs to the CDC50/LEM3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NV96-1	1	yes
Q9NV96-2	2
Q9NV96-3	3

RefSeq proteins (2): NP_001137430, NP_060717* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005045	CDC50/LEM3_fam	Family

Pfam: PF03381

UniProt features (56 total): strand 18, helix 13, glycosylation site 4, turn 4, disulfide bond 3, mutagenesis site 3, topological domain 3, splice variant 2, transmembrane region 2, initiator methionine 1, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8OX6	ELECTRON MICROSCOPY	2.39
9VKG	ELECTRON MICROSCOPY	2.39
9VNT	ELECTRON MICROSCOPY	2.51
8OX7	ELECTRON MICROSCOPY	2.56
8OXC	ELECTRON MICROSCOPY	2.58
8OX9	ELECTRON MICROSCOPY	2.72
8OXA	ELECTRON MICROSCOPY	2.76
6K7L	ELECTRON MICROSCOPY	2.83
6K7N	ELECTRON MICROSCOPY	2.84
9VSL	ELECTRON MICROSCOPY	2.88
8OX5	ELECTRON MICROSCOPY	2.9
6K7M	ELECTRON MICROSCOPY	2.95
8OX8	ELECTRON MICROSCOPY	2.98
8OXB	ELECTRON MICROSCOPY	2.99
7BSV	ELECTRON MICROSCOPY	3
6K7K	ELECTRON MICROSCOPY	3.04
6K7J	ELECTRON MICROSCOPY	3.08
7PY4	ELECTRON MICROSCOPY	3.1
7BSQ	ELECTRON MICROSCOPY	3.2
7BSU	ELECTRON MICROSCOPY	3.2
6K7H	ELECTRON MICROSCOPY	3.22
6K7I	ELECTRON MICROSCOPY	3.22
6K7G	ELECTRON MICROSCOPY	3.3
7BSS	ELECTRON MICROSCOPY	3.3
7VGI	ELECTRON MICROSCOPY	3.36
7VSH	ELECTRON MICROSCOPY	3.4
8OX4	ELECTRON MICROSCOPY	3.4
9VQ2	ELECTRON MICROSCOPY	3.4
6LKN	X-RAY DIFFRACTION	3.9
7BSW	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NV96-F1	90.09	0.75

Functional residue map

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

Post-translational modifications (1): 2

Disulfide bonds (3): 91–104, 94–102, 157–171

Glycosylation sites (4): 180, 190, 294, 107

Mutagenesis-validated functional residues (3):

Position	Phenotype
132	decreases ps- and pe-dependent atpase activity of atp11c:tmem30a; when associated with a-133 and a-136.
133	decreases ps- and pe-dependent atpase activity of atp11c:tmem30a; when associated with a-132 and a-136.
136	decreases ps- and pe-dependent atpase activity of atp11c:tmem30a; when associated with a-132 and a-133.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 243 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GCM_MAP4K4, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, CGGAARNGGCNG_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEUROGENESIS, GOBP_XENOBIOTIC_TRANSMEMBRANE_TRANSPORT

GO Biological Process (9): xenobiotic transmembrane transport (GO:0006855), positive regulation of neuron projection development (GO:0010976), aminophospholipid transport (GO:0015917), protein localization to endosome (GO:0036010), phospholipid translocation (GO:0045332), positive regulation of phospholipid translocation (GO:0061092), positive regulation of protein exit from endoplasmic reticulum (GO:0070863), lipid transport (GO:0006869), aminophospholipid translocation (GO:0140331)

GO Molecular Function (3): structural molecule activity (GO:0005198), aminophospholipid flippase activity (GO:0015247), protein binding (GO:0005515)

GO Cellular Component (12): endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), transport vesicle membrane (GO:0030658), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), azurophil granule membrane (GO:0035577), specific granule membrane (GO:0035579), phospholipid-translocating ATPase complex (GO:1990531), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
phospholipid transport	2
phospholipid translocation	2
endomembrane system	2
intracellular membrane-bounded organelle	2
endosome membrane	2
secretory granule membrane	2
xenobiotic transport	1
transmembrane transport	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
nitrogen compound transport	1
protein localization to organelle	1
lipid translocation	1
positive regulation of cellular component organization	1
regulation of phospholipid translocation	1
positive regulation of phospholipid transport	1
protein exit from endoplasmic reticulum	1
regulation of protein exit from endoplasmic reticulum	1
positive regulation of intracellular protein transport	1
transport	1
lipid localization	1
aminophospholipid transport	1
molecular_function	1
flippase activity	1
aminophospholipid translocation	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
transport vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
early endosome	1
late endosome	1
lysosomal membrane	1
azurophil granule	1

Protein interactions and networks

STRING

982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC50A	ATP8A1	Q9Y2Q0	989
CDC50A	ATP11C	Q8NB49	947
CDC50A	ATP8B1	O43520	859
CDC50A	ATP8B2	P98198	834
CDC50A	ATP11A	P98196	794
CDC50A	ATP8A2	Q9NTI2	737
CDC50A	ATP11B	Q9Y2G3	717
CDC50A	ATP9A	O75110	660
CDC50A	ATP9B	O43861	651
CDC50A	ATP10D	Q9P241	639
CDC50A	ATP10B	O94823	615
CDC50A	ATP10A	O60312	614
CDC50A	ATP8B4	Q8TF62	583
CDC50A	XKR8	Q9H6D3	580
CDC50A	ATP8B3	O60423	578

IntAct

144 interactions, top by confidence:

A	B	Type	Score
ATP8B1	TMEM30A	psi-mi:“MI:0915”(physical association)	0.880
ATP8B1	TMEM30A	psi-mi:“MI:0403”(colocalization)	0.880
TMEM30A	ATP8B1	psi-mi:“MI:0915”(physical association)	0.880
TMEM30A	ATP11A	psi-mi:“MI:0915”(physical association)	0.800
ATP11A	TMEM30A	psi-mi:“MI:0915”(physical association)	0.800
TMEM30A	ATP8A1	psi-mi:“MI:0915”(physical association)	0.740
ATP8A1	TMEM30A	psi-mi:“MI:0915”(physical association)	0.740
ATP8A1	TMEM30A	psi-mi:“MI:0403”(colocalization)	0.740
TMEM30A	ATP11C	psi-mi:“MI:0915”(physical association)	0.690
ATP11C	TMEM30A	psi-mi:“MI:0915”(physical association)	0.690
ATP10A	TMEM30A	psi-mi:“MI:0915”(physical association)	0.660
ATP8B2	TMEM30A	psi-mi:“MI:0915”(physical association)	0.650
ATP8B4	TMEM30A	psi-mi:“MI:0915”(physical association)	0.650
ATP8B4	TMEM30A	psi-mi:“MI:0403”(colocalization)	0.650
ATP8B2	TMEM30A	psi-mi:“MI:0403”(colocalization)	0.650
TMEM30A	ATP8B4	psi-mi:“MI:0915”(physical association)	0.650
TMEM30A	ATP8B2	psi-mi:“MI:0915”(physical association)	0.650

BioGRID (252): ATP8A1 (Affinity Capture-Western), TMEM30A (Affinity Capture-MS), LSR (Affinity Capture-MS), HLA-C (Affinity Capture-MS), BACE2 (Affinity Capture-MS), CLCC1 (Affinity Capture-MS), LPHN1 (Affinity Capture-MS), SARAF (Affinity Capture-MS), NSDHL (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), APP (Affinity Capture-MS), DHRS7 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), ACVR1B (Affinity Capture-MS), MARC1 (Affinity Capture-MS)

ESM2 similar proteins: A5A6J8, P05026, P05027, P05028, P05029, P06583, P07340, P08251, P13638, P14094, P14231, P14415, P18434, P18597, P18598, P21188, P30715, P30716, P33704, P33879, P43002, P50992, P51164, P51165, P51575, P51577, P54709, Q17QL5, Q202B1, Q24048, Q28030, Q2HZ96, Q4R4V5, Q5E9U1, Q5F362, Q5J583, Q5R6C0, Q5R8S8, Q6AY41, Q8L8W0

Diamond homologs: A0ZSE6, A0ZT23, Q17QL5, Q2T9P5, Q5F362, Q5R6C0, Q8VEK0, Q95JK4, Q9D4D7, Q9NV96, H2L0H3, Q6AY41, Q8L8W0, Q9LTW0, G0SDN0, P25656, P42838, P53740, Q1MTQ5, Q96WW4, Q9SA35, Q9SLK2, Q3MIR4, Q67YS6, Q8BHG3, S7WII9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	6	22.3×	2e-05
Ion transport by P-type ATPases	11	21.6×	9e-10
Ion channel transport	12	10.9×	1e-07
ER-Phagosome pathway	7	8.6×	8e-04
R-HSA-425393	7	8.6×	8e-04
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	10	8.2×	3e-05
Interferon gamma signaling	6	7.1×	7e-03
Transport of small molecules	23	5.5×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
phospholipid translocation	12	55.5×	6e-16
positive regulation of T cell mediated cytotoxicity	6	22.7×	8e-05
monoatomic ion transmembrane transport	8	12.3×	8e-05
amino acid transport	5	11.6×	6e-03
transport across blood-brain barrier	8	10.6×	2e-04
monoatomic ion transport	7	8.1×	3e-03
immune response	13	4.5×	8e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1278 predictions. Top by Δscore:

Variant	Effect	Δscore
6:75259341:TTTTA:T	donor_loss	1.0000
6:75259342:TTTA:T	donor_loss	1.0000
6:75259343:TTACC:T	donor_loss	1.0000
6:75259344:TACCT:T	donor_loss	1.0000
6:75259345:A:AG	donor_loss	1.0000
6:75259346:C:T	donor_loss	1.0000
6:75259441:G:T	acceptor_gain	1.0000
6:75259491:C:CC	acceptor_gain	1.0000
6:75259794:T:TA	donor_gain	1.0000
6:75260907:GGATT:G	acceptor_gain	1.0000
6:75260908:GATT:G	acceptor_gain	1.0000
6:75260909:ATT:A	acceptor_gain	1.0000
6:75260910:TT:T	acceptor_gain	1.0000
6:75260911:TC:T	acceptor_loss	1.0000
6:75260912:C:CC	acceptor_gain	1.0000
6:75260912:CTG:C	acceptor_loss	1.0000
6:75260916:T:TC	acceptor_gain	1.0000
6:75260917:T:C	acceptor_gain	1.0000
6:75260917:T:TC	acceptor_gain	1.0000
6:75260918:T:C	acceptor_gain	1.0000
6:75260918:T:TC	acceptor_gain	1.0000
6:75260919:T:C	acceptor_gain	1.0000
6:75260919:T:TC	acceptor_gain	1.0000
6:75260922:C:CT	acceptor_gain	1.0000
6:75260923:A:T	acceptor_gain	1.0000
6:75265225:A:AC	donor_gain	1.0000
6:75265225:ACTT:A	donor_loss	1.0000
6:75265226:C:CC	donor_gain	1.0000
6:75265226:CTT:C	donor_loss	1.0000
6:75265227:TTA:T	donor_loss	1.0000

AlphaMissense

2385 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:75256264:T:A	K308N	1.000
6:75256264:T:G	K308N	1.000
6:75258865:A:C	F269L	1.000
6:75258865:A:T	F269L	1.000
6:75258867:A:G	F269L	1.000
6:75258887:C:G	R262P	1.000
6:75258892:C:A	W260C	1.000
6:75258892:C:G	W260C	1.000
6:75258894:A:G	W260R	1.000
6:75258894:A:T	W260R	1.000
6:75259390:G:C	F214L	1.000
6:75259390:G:T	F214L	1.000
6:75259392:A:G	F214L	1.000
6:75259490:T:A	D181V	1.000
6:75260824:C:G	D181H	1.000
6:75260841:G:T	A175D	1.000
6:75260850:C:A	G172V	1.000
6:75260850:C:T	G172E	1.000
6:75260851:C:G	G172R	1.000
6:75260851:C:T	G172R	1.000
6:75260852:A:C	C171W	1.000
6:75260853:C:T	C171Y	1.000
6:75260895:C:G	C157S	1.000
6:75260895:C:T	C157Y	1.000
6:75260896:A:G	C157R	1.000
6:75260896:A:T	C157S	1.000
6:75265256:A:G	L143P	1.000
6:75265271:C:G	R138P	1.000
6:75265294:G:C	N130K	1.000
6:75265294:G:T	N130K	1.000

dbSNP variants (sampled 300 via entrez): RS1000013993 (6:75256978 G>A), RS1000066275 (6:75257266 C>A,T), RS1000141936 (6:75279634 A>G), RS1000167542 (6:75253743 G>A,T), RS1000335368 (6:75268477 T>C,G), RS1000499712 (6:75255515 G>A), RS1000502734 (6:75283365 C>G), RS1000617405 (6:75282995 C>T), RS1000658231 (6:75255840 G>A), RS1000734040 (6:75260933 A>G), RS1000770383 (6:75275594 T>C), RS1000920008 (6:75280747 A>G), RS1001068528 (6:75255475 G>A), RS1001101856 (6:75262890 G>A), RS1001219047 (6:75262922 T>G)

Disease associations

OMIM: gene MIM:611028 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Tetrachlorodibenzodioxin	increases expression	3
bisphenol A	increases methylation, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol F	increases expression	1
trichostatin A	affects expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Coumestrol	decreases expression	1
Demecolcine	increases expression	1
Diethylstilbestrol	decreases expression	1
Diuron	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Methylcholanthrene	affects binding, increases reaction, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2IT	Abcam HeLa TMEM30A KO	Cancer cell line	Female
CVCL_F2AI	CDC50A-OE	Cancer cell line	Female
CVCL_TS94	HAP1 TMEM30A (-) 1	Cancer cell line	Male
CVCL_XU50	HAP1 TMEM30A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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