FXYD1

Summary

FXYD1 (FXYD domain containing ion transport regulator 1, HGNC:4025) is a protein-coding gene on chromosome 19q13.12, encoding Phospholemman (O00168). Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell.

This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. The protein encoded by this gene is a plasma membrane substrate for several kinases, including protein kinase A, protein kinase C, NIMA kinase, and myotonic dystrophy kinase. It is thought to form an ion channel or regulate ion channel activity. Transcript variants with different 5’ UTR sequences have been described in the literature.

Source: NCBI Gene 5348 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_021902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4025
Approved symbol	FXYD1
Name	FXYD domain containing ion transport regulator 1
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000266964
Ensembl biotype	protein_coding
OMIM	602359
Entrez	5348

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 40 protein_coding, 3 retained_intron

ENST00000351325, ENST00000455515, ENST00000587056, ENST00000588081, ENST00000588607, ENST00000588715, ENST00000589121, ENST00000589209, ENST00000590462, ENST00000592818, ENST00000612146, ENST00000874897, ENST00000874898, ENST00000874899, ENST00000874900, ENST00000874901, ENST00000874902, ENST00000874903, ENST00000874904, ENST00000874905, ENST00000874906, ENST00000874907, ENST00000874908, ENST00000874909, ENST00000874910, ENST00000874911, ENST00000874912, ENST00000874913, ENST00000874914, ENST00000874915, ENST00000874916, ENST00000874917, ENST00000874918, ENST00000874919, ENST00000874920, ENST00000874921, ENST00000874922, ENST00000874923, ENST00000874924, ENST00000874925, ENST00000874926, ENST00000874927, ENST00000874928

RefSeq mRNA: 4 — MANE Select: NM_021902 NM_001278717, NM_001278718, NM_005031, NM_021902

CCDS: CCDS12445

Canonical transcript exons

ENST00000351325 — 8 exons

Exon	Start	End
ENSE00001395903	35142917	35143109
ENSE00002846763	35138824	35138894
ENSE00003463322	35141536	35141572
ENSE00003472571	35140076	35140140
ENSE00003507899	35142472	35142521
ENSE00003551774	35140597	35140629
ENSE00003660543	35141132	35141206
ENSE00003692671	35142720	35142771

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.54.

FANTOM5 (CAGE): breadth broad, TPM avg 16.6742 / max 647.0616, expressed in 690 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175212	9.4849	589
175211	1.4430	380
175213	1.2994	225
175222	0.8618	211
175216	0.7129	191
175214	0.6799	270
175221	0.6511	143
175215	0.4006	150
175220	0.3757	132
175226	0.2031	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.54	gold quality
apex of heart	UBERON:0002098	99.52	gold quality
tibial nerve	UBERON:0001323	99.46	gold quality
gastrocnemius	UBERON:0001388	99.46	gold quality
skeletal muscle tissue	UBERON:0001134	99.33	gold quality
right coronary artery	UBERON:0001625	99.30	gold quality
right atrium auricular region	UBERON:0006631	99.27	gold quality
heart left ventricle	UBERON:0002084	99.24	gold quality
muscle of leg	UBERON:0001383	99.22	gold quality
putamen	UBERON:0001874	99.19	gold quality
popliteal artery	UBERON:0002250	99.18	gold quality
tibial artery	UBERON:0007610	99.18	gold quality
caudate nucleus	UBERON:0001873	99.17	gold quality
right lobe of liver	UBERON:0001114	99.13	gold quality
nucleus accumbens	UBERON:0001882	99.12	gold quality
amygdala	UBERON:0001876	99.06	gold quality
temporal lobe	UBERON:0001871	99.03	gold quality
mucosa of stomach	UBERON:0001199	99.02	gold quality
left coronary artery	UBERON:0001626	99.02	gold quality
substantia nigra	UBERON:0002038	99.00	gold quality
ascending aorta	UBERON:0001496	98.99	gold quality
thoracic aorta	UBERON:0001515	98.99	gold quality
endocervix	UBERON:0000458	98.98	gold quality
heart	UBERON:0000948	98.91	gold quality
left uterine tube	UBERON:0001303	98.90	gold quality
descending thoracic aorta	UBERON:0002345	98.89	gold quality
body of uterus	UBERON:0009853	98.68	gold quality
Ammon’s horn	UBERON:0001954	98.64	gold quality
muscle tissue	UBERON:0002385	98.60	gold quality
liver	UBERON:0002107	98.57	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	2484.59
E-MTAB-8410	yes	2378.76
E-GEOD-135922	yes	1366.18
E-CURD-126	yes	886.62
E-MTAB-10485	yes	278.62
E-HCAD-1	yes	75.93
E-ENAD-20	yes	73.65
E-MTAB-10287	yes	69.34
E-HCAD-10	yes	35.90
E-MTAB-10553	yes	33.52
E-ANND-3	yes	25.64
E-CURD-46	yes	18.17
E-GEOD-84465	yes	12.96
E-GEOD-134144	yes	8.63
E-MTAB-10042	yes	8.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MECP2

miRNA regulators (miRDB)

5 targeting FXYD1, 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-3196	98.96	63.91	326
HSA-MIR-764	94.16	64.85	656
HSA-MIR-6853-5P	93.94	61.88	114
HSA-MIR-3178	89.40	60.05	100
HSA-MIR-6770-3P	88.39	62.36	71

Literature-anchored findings (GeneRIF, showing 27)

• molecular cloning, protein expression, sequencing and NMR structure determination (PMID:12535606)
• show that the helical regions and connecting segments of FXYD1, FXYD3, and FXYD4 determined in micelles by NMR spectroscopy coincide with the positions of intron-exon junctions in the genes (PMID:16288923)
• PLM interacts with the intracellular loop of NCX1, most likely at residues 218-358 (PMID:16921169)
• study reports that FXYD1 is elevated in frontal cortex neurons of Rett syndrome patients and Mecp2-null mice; FXYD1 is identified as a MeCP2 target gene whose de-repression may directly contribute to RTT neuronal pathogenesis (PMID:17309881)
• the structure of FXYD1 suggests a mechanism whereby the phosphorylation of conserved Ser residues, by protein kinases A and C, could induce a conformational change in the cytoplasmic domain, to modulate its interaction with the Na,K-ATPase, alpha subunit (PMID:18000745)
• reconstituted FXYD1 protects both alpha1beta1 and alpha2beta1 very strongly against thermal inactivation (PMID:18052210)
• Data show that PLM associates with and modulates both NKA-alpha1 and NKA-alpha2 in a comparable but not identical manner. (PMID:19638348)
• Study reveals, in various human tissues, the specific expression of FXYD1, which may associate with Na, K-ATPase in selected cell types and modulate its catalytic properties. (PMID:19879113)
• Phospholemman modulates the gating of cardiac L-type calcium channels (PMID:20371314)
• Data suggest that phospholemman plays an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca(2+) dynamics in the heart. (PMID:20720179)
• PLM phosphorylation at either Ser63 or Ser68 is both necessary and sufficient for completely relieving the PLM-induced NKA inhibition. (PMID:20861470)
• Results suggest that the PLM cytoplasmic domain populates NKA-associated and membrane-associated states in dynamic equilibrium and that phosphorylation may alter the position of the equilibrium. (PMID:21130070)
• phosphorylation of PLM increases its oligomerization into tetramers, decreases its binding to NKA, and alters the structures of both the tetramer and NKA regulatory complex. (PMID:21220422)
• FXYD1 raises the affinity of the human alpha1beta1 isoform of Na,K-ATPase for Na ions (PMID:21449573)
• in left ventricular myocardium from patients with heart failure, PLM Ser-68 phosphorylation was approximately 50% lower than in nonfailing controls (PMID:21849407)
• Exercise induces FXYD1 phosphorylation at multiple sites in human muscle; in mice, contraction-induced changes in FXYD1 phosphorylation are fiber-type specific and dependent on protein kinase Calpha activity. (PMID:21957166)
• the severity of the spinal cord lesion is an important factor controlling the expression of Na(+)-K(+)-ATPase and its regulatory protein PLM (PMID:22275761)
• Intracellular trafficking of FXYD1 (phospholemman) and FXYD7 proteins in Xenopus oocytes and mammalian cells. (PMID:22535957)
• PLM regulates important ion transporters in the heart and offers a tempting target for development of drugs to treat heart failure. (PMID:23224879)
• Phospholemman is the target of a variety of post-translational modifications and these can dynamically alter the activity of the Na pump. [Review] (PMID:23672825)
• the evolutionary conservation of G-quadruplex forming sequences with the confirmation of G-quadruplex formation in vitro by two FXYD1 homologues (PMID:25051342)
• Study demonstrated that the expression of FXYD1, FXYD3 and FXYD5 is elevated in the lungs of Acute respiratory distress syndrome patients (PMID:26410457)
• Stopped-flow experiments using the dye RH421 show that FXYD1 slows the conformational transition E2(2K)ATP –> E1(3Na)ATP but does not affect 3NaE1P –> E2P3Na. (PMID:26429909)
• a period of high-intensity training with reduced training volume increases expression and phosphorylation levels of FXYD1, which may affect Na(+)/K(+) pump activity and muscle K(+) homeostasis during intense exercise. (PMID:26791827)
• Blood flow restriction augmented exercise-induced increases in muscle FXYD1 and PGC-1alpha mRNA in men (PMID:29383885)
• FXYD protein isoforms differentially modulate human Na/K pump function. (PMID:33231612)
• Expression mode and prognostic value of FXYD family members in colon cancer. (PMID:34270462)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fxyd1	ENSMUSG00000036570
rattus_norvegicus	Fxyd1	ENSRNOG00000021079

Paralogs (6): FXYD5 (ENSG00000089327), FXYD3 (ENSG00000089356), FXYD6 (ENSG00000137726), FXYD2 (ENSG00000137731), FXYD4 (ENSG00000150201), FXYD7 (ENSG00000221946)

Protein

Protein identifiers

Phospholemman — O00168 (reviewed: O00168)

Alternative names: FXYD domain-containing ion transport regulator 1, Sodium/potassium-transporting ATPase subunit FXYD1

All UniProt accessions (2): O00168, K7EQG4

UniProt curated annotations — full annotation on UniProt →

Function. Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell. Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated. Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1. Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone.

Subunit / interactions. Homotetramer. Monomer. Regulatory subunit of the sodium/potassium-transporting ATPase (NKA) which is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. The monomeric form associates with NKA while the oligomeric form does not. Interacts with the catalytic alpha-1 subunit ATP1A1. Also interacts with the catalytic alpha-2 and alpha-3 subunits ATP1A2 and ATP1A3. Very little interaction with ATP1A1, ATP1A2 or ATP1A3 when phosphorylated at Ser-83. Interacts with the non-catalytic beta-1 subunit ATP1B1. Oxidative stress decreases interaction with ATP1A1 but increases interaction with ATP1B1.

Subcellular location. Cell membrane. Sarcolemma. Apical cell membrane. Membrane. Caveola. T-tubule.

Tissue specificity. Highest expression in skeletal muscle and heart. Moderate levels in brain, placenta, lung, liver, pancreas, uterus, bladder, prostate, small intestine and colon with mucosal lining. Very low levels in kidney, colon and small intestine without mucosa, prostate without endothelial lining, spleen, and testis.

Post-translational modifications. Major plasma membrane substrate for cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in several different tissues. Phosphorylated in response to insulin and adrenergic stimulation. Phosphorylation at Ser-88 stimulates sodium/potassium-transporting ATPase activity while the unphosphorylated form inhibits sodium/potassium-transporting ATPase activity. Phosphorylation increases tetramerization, decreases binding to ATP1A1 and reduces inhibition of ATP1A1 activity. Phosphorylation at Ser-83 leads to greatly reduced interaction with ATP1A1, ATP1A2 and ATP1A3. May be phosphorylated by DMPK. Palmitoylation increases half-life and stability and is enhanced upon phosphorylation at Ser-88 by PKA.

Domain organisation. The cytoplasmic domain is sufficient to regulate sodium/potassium-transporting ATPase activity.

Similarity. Belongs to the FXYD family.

RefSeq proteins (4): NP_001265646, NP_001265647, NP_005022, NP_068702* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000272	Ion-transport_regulator_FXYD	Family
IPR047281	PLM	Family
IPR047297	FXYD_motif	Conserved_site

Pfam: PF02038

UniProt features (26 total): modified residue 6, helix 4, lipid moiety-binding region 2, mutagenesis site 2, sequence conflict 2, topological domain 2, turn 2, signal peptide 1, chain 1, strand 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2JO1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00168-F1	71.01	0.06

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 (8): 83, 88, 89, 60, 62, 62, 79, 82

Mutagenesis-validated functional residues (2):

Position	Phenotype
60	significantly reduced half-life; when associated with s-62.
62	significantly reduced half-life; when associated with s-60.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5578775	Ion homeostasis
R-HSA-936837	Ion transport by P-type ATPases
R-HSA-9679191	Potential therapeutics for SARS

MSigDB gene sets: 237 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, MYOGENIN_Q6, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_64, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_INORGANIC_ANION_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, MODULE_329, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, MODULE_66

GO Biological Process (12): potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), chloride transport (GO:0006821), muscle contraction (GO:0006936), regulation of heart contraction (GO:0008016), negative regulation of protein glutathionylation (GO:0010734), regulation of cardiac muscle cell membrane potential (GO:0086036), positive regulation of sodium ion export across plasma membrane (GO:1903278), monoatomic ion transport (GO:0006811), regulation of monoatomic ion transport (GO:0043269), regulation of sodium ion transmembrane transport (GO:1902305), chloride transmembrane transport (GO:1902476)

GO Molecular Function (4): chloride channel activity (GO:0005254), sodium channel regulator activity (GO:0017080), transmembrane transporter binding (GO:0044325), ion channel regulator activity (GO:0099106)

GO Cellular Component (8): plasma membrane (GO:0005886), sodium:potassium-exchanging ATPase complex (GO:0005890), caveola (GO:0005901), intercalated disc (GO:0014704), apical plasma membrane (GO:0016324), T-tubule (GO:0030315), sarcolemma (GO:0042383), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cardiac conduction	1
Ion channel transport	1
SARS-CoV Infections	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion transport	2
cellular anatomical structure	2
monoatomic anion transport	1
inorganic anion transport	1
muscle system process	1
heart contraction	1
regulation of blood circulation	1
protein glutathionylation	1
regulation of protein glutathionylation	1
negative regulation of protein modification process	1
regulation of membrane potential	1
sodium ion export across plasma membrane	1
positive regulation of sodium ion transmembrane transport	1
regulation of sodium ion export across plasma membrane	1
transport	1
monoatomic ion transport	1
regulation of transport	1
regulation of sodium ion transport	1
sodium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
sodium channel activity	1
ion channel regulator activity	1
protein binding	1
monoatomic ion channel activity	1
channel regulator activity	1
membrane	1
cell periphery	1
cation-transporting ATPase complex	1
plasma membrane protein complex	1
plasma membrane raft	1
cell-cell contact zone	1
apical part of cell	1
plasma membrane region	1
sarcolemma	1
plasma membrane	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FXYD1	TAC1	P20366	747
FXYD1	MECP2	P51608	699
FXYD1	ZDHHC5	Q9C0B5	694
FXYD1	FXYD5	Q96DB9	689
FXYD1	CAV3	P56539	593
FXYD1	SERPINF2	P08697	585
FXYD1	TUBA1B	P04687	585
FXYD1	GPRIN1	Q7Z2K8	546
FXYD1	ADRB1	P08588	530
FXYD1	FXYD4	P59646	529
FXYD1	LRRC8A	Q8IWT6	518
FXYD1	FLOT2	Q14254	518
FXYD1	GAMT	Q14353	504
FXYD1	CACNA1C	Q13936	487
FXYD1	CLDND1	Q9NY35	483

IntAct

6 interactions, top by confidence:

A	B	Type	Score
FXYD1	GCHFR	psi-mi:“MI:0914”(association)	0.530
ATP1A1	FXYD1	psi-mi:“MI:0915”(physical association)	0.400
FXYD1	SPINK4	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): FXYD1 (Synthetic Growth Defect), NDRG1 (Affinity Capture-MS), NDRG3 (Affinity Capture-MS), NDRG4 (Affinity Capture-MS), THNSL1 (Affinity Capture-MS), GCHFR (Affinity Capture-MS), ATP6V1D (Affinity Capture-MS), GOPC (Affinity Capture-MS), FAM204A (Affinity Capture-MS), PRTFDC1 (Affinity Capture-MS), POLE4 (Affinity Capture-MS), FXYD1 (Reconstituted Complex), FXYD1 (Affinity Capture-Western), FXYD1 (Affinity Capture-Western), FXYD1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GST9, A0A1B0GTU2, A0A1B0GV90, A0A590UK83, A2RRL7, A7S641, A8WG88, A9JTJ0, B9X187, K7EJ46, O00168, O08589, O13001, P0C2S0, P15383, P41237, P56513, P60606, P63160, P63161, Q04645, Q04646, Q04679, Q04680, Q0P467, Q28EH9, Q3SZX0, Q3UJ81, Q3URE8, Q3ZBP2, Q4LDR2, Q4R6L9, Q502I1, Q592E4, Q5XF36, Q6AXF6, Q6NWH5, Q6PBK8, Q6Q3F5, Q71RC9

Diamond homologs: G1TZA0, I3LMB3, O00168, O08589, O13001, O97797, P54710, P56513, P58549, P58550, P59645, P59646, P59647, P59648, P59649, Q04645, Q04646, Q04679, Q04680, Q14802, Q3MHZ5, Q3SZX0, Q3ZBJ3, Q4R566, Q5RB29, Q61835, Q63113, Q91XV6, Q96DB9, Q9D164, Q9D2W0, Q9H0Q3, Q9Z239, W5P3P0, P97808, C0HJJ0

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKACA	unknown	FXYD1	phosphorylation
PRKACA	“up-regulates activity”	FXYD1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

877 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35141108:C:G	acceptor_gain	1.0000
19:35141115:T:TA	acceptor_gain	1.0000
19:35141120:T:TA	acceptor_gain	1.0000
19:35141123:T:TA	acceptor_gain	1.0000
19:35141127:CACAG:C	acceptor_loss	1.0000
19:35141128:ACAGA:A	acceptor_loss	1.0000
19:35141129:C:G	acceptor_gain	1.0000
19:35141130:A:AG	acceptor_gain	1.0000
19:35141131:G:GG	acceptor_gain	1.0000
19:35141131:GAC:G	acceptor_gain	1.0000
19:35141202:GC:G	donor_gain	1.0000
19:35141202:GCTGA:G	donor_gain	1.0000
19:35141203:C:G	donor_gain	1.0000
19:35141204:TGA:T	donor_gain	1.0000
19:35141205:GA:G	donor_gain	1.0000
19:35141205:GAG:G	donor_gain	1.0000
19:35141206:AG:A	donor_loss	1.0000
19:35141207:G:GG	donor_gain	1.0000
19:35141207:GT:G	donor_loss	1.0000
19:35141527:C:CA	acceptor_gain	1.0000
19:35141569:AGAGG:A	donor_loss	1.0000
19:35141570:GAG:G	donor_gain	1.0000
19:35141571:AGG:A	donor_loss	1.0000
19:35141572:GGTAA:G	donor_loss	1.0000
19:35141573:G:GG	donor_gain	1.0000
19:35141573:GT:G	donor_loss	1.0000
19:35141574:T:A	donor_loss	1.0000
19:35142469:CAG:C	acceptor_loss	1.0000
19:35142470:A:AG	acceptor_gain	1.0000
19:35142470:A:AT	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000616306 (19:35135412 G>A,T), RS1000911485 (19:35135368 T>C), RS1001085235 (19:35139624 G>A), RS1001348082 (19:35138281 A>G), RS1002076313 (19:35139484 C>T), RS1002086088 (19:35139665 G>A,C), RS1002736826 (19:35142857 G>A), RS1003374188 (19:35141419 T>C,G), RS1003439478 (19:35135950 C>T), RS1004693570 (19:35135581 G>T), RS1004874934 (19:35142753 A>G), RS1005416447 (19:35136316 C>G,T), RS1006354791 (19:35143523 T>C), RS1006707278 (19:35138170 T>TA), RS1006888990 (19:35139858 G>A,C,T)

Disease associations

OMIM: gene MIM:602359 | 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 — Na⁺/K⁺-ATPases

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
bisphenol A	affects expression, affects cotreatment, increases methylation	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression	2
Estradiol	decreases expression	2
Valproic Acid	decreases expression, increases expression, increases methylation	2
ethyl-p-hydroxybenzoate	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Allergens	decreases expression, affects cotreatment, increases abundance	1
Amiodarone	increases expression	1
Ampicillin	increases expression	1
Vehicle Emissions	affects cotreatment, decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Doxorubicin	affects expression	1
Lead	affects expression	1
Nickel	decreases expression	1
Quercetin	affects expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Oxyquinoline	increases expression	1
Aflatoxin B1	decreases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Copper Sulfate	decreases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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