FXYD2

FXYD domain containing ion transport regulator 2

Basic information

Region (hg38): 11:117800844-117828698

Previous symbols: [ "ATP1G1", "HOMG2" ]

Links

ENSG00000137731NCBI:486OMIM:601814HGNC:4026Uniprot:P54710AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • renal hypomagnesemia 2 (Supportive), mode of inheritance: AD
  • renal hypomagnesemia 2 (Strong), mode of inheritance: AD
  • renal hypomagnesemia 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypomagnesemia 2, renalADRenalSurveillance for and treatment of electrolyte abnormalities can be beneficial (eg, to avoid sequelae such as pseudogout, as has been described in affected individuals)Renal3298795; 11062458

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FXYD2 gene.

  • not provided (1 variants)
  • Renal hypomagnesemia 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FXYD2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
11
clinvar
3
clinvar
15
missense
1
clinvar
9
clinvar
2
clinvar
12
nonsense
0
start loss
0
frameshift
1
clinvar
1
inframe indel
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
2
splice region
7
6
13
non coding
3
clinvar
9
clinvar
22
clinvar
34
Total 1 0 15 23 25

Variants in FXYD2

This is a list of pathogenic ClinVar variants found in the FXYD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
11-117820164-C-T Renal hypomagnesemia 2 Benign (Jan 12, 2018)302513
11-117820191-G-A Renal Hypomagnesemia, Dominant Uncertain significance (Jun 14, 2016)302514
11-117820203-A-C Renal hypomagnesemia 2 Benign (Jan 13, 2018)302515
11-117820230-T-C Renal hypomagnesemia 2 Uncertain significance (Jan 13, 2018)878676
11-117820255-A-T Renal hypomagnesemia 2 Uncertain significance (Jan 13, 2018)302516
11-117820274-G-A Renal hypomagnesemia 2 Benign (Jan 12, 2018)302517
11-117820301-G-T Renal hypomagnesemia 2 Benign (Jan 13, 2018)302518
11-117820308-C-T Renal hypomagnesemia 2 Benign (Jan 13, 2018)302519
11-117820430-C-T Benign (Nov 11, 2018)1243897
11-117820433-C-T Benign (Nov 11, 2018)1272007
11-117820548-C-A Likely benign (Nov 08, 2020)1317355
11-117820637-C-T Benign (May 24, 2021)1248580
11-117820660-G-T Renal hypomagnesemia 2 • not specified Benign/Likely benign (Nov 22, 2019)302520
11-117820665-C-G FXYD2-related disorder Likely benign (Aug 24, 2020)3032041
11-117820666-C-A FXYD2-related disorder Likely benign (Dec 20, 2022)3053963
11-117820671-G-A Renal hypomagnesemia 2 Benign (Nov 26, 2019)302521
11-117820675-C-A Renal hypomagnesemia 2 Benign/Likely benign (Oct 10, 2022)724848
11-117820675-C-T Renal hypomagnesemia 2 Likely benign (Mar 18, 2022)755271
11-117820678-C-T Renal hypomagnesemia 2 Benign (Jan 16, 2024)302522
11-117820681-A-G FXYD6-FXYD2-related disorder Likely benign (Aug 09, 2022)2170273
11-117820686-C-T Uncertain significance (Jun 26, 2023)3000085
11-117820688-T-C not specified Uncertain significance (Dec 20, 2023)2691353
11-117820690-G-A Renal hypomagnesemia 2 Benign/Likely benign (May 12, 2023)302523
11-117820702-G-A Likely benign (Nov 10, 2023)2186659
11-117820702-G-T Likely benign (Nov 13, 2023)2974773

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
FXYD2protein_codingprotein_codingENST00000292079 527855
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.1140.787125469021254710.00000797
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1564946.01.060.00000312426
Missense in Polyphen2017.9631.1134185
Synonymous-0.9772317.81.290.00000130114
Loss of Function1.3025.210.3842.21e-767

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.00006540.0000654
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.;
Pathway
Cardiac muscle contraction - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Bile secretion - Homo sapiens (human);Carbohydrate digestion and absorption - Homo sapiens (human);Proximal tubule bicarbonate reclamation - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Mineral absorption - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Diuretics Pathway, Pharmacodynamics;Levomethadyl Acetate Action Action Pathway;Polythiazide Action Pathway;Methyclothiazide Action Pathway;Bumetanide Action Pathway;Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Spironolactone Action Pathway;Eplerenone Action Pathway;Triamterene Action Pathway;Amiloride Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Bevantolol Action Pathway;Practolol Action Pathway;Trehalose Degradation;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Ethacrynic Acid Action Pathway;Quinethazone Action Pathway;Bendroflumethiazide Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Nicotine Action Pathway;Chlorthalidone Action Pathway;Trichlormethiazide Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Iminoglycinuria;Lysinuric Protein Intolerance;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Muscle/Heart Contraction;Blue diaper syndrome;Lysinuric protein intolerance (LPI);Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Bupranolol Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Nebivolol Action Pathway;Cystinuria;Amlodipine Action Pathway;Verapamil Action Pathway;Indapamide Action Pathway;Furosemide Action Pathway;Torsemide Action Pathway;Hartnup Disorder;Glucose Transporter Defect (SGLT2);Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Kidney Function;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Glucose Transporter Defect (SGLT2);Carvedilol Action Pathway;Labetalol Action Pathway;Lactose Degradation;Lactose Intolerance;Metolazone Action Pathway;Hydrochlorothiazide Action Pathway;Cyclothiazide Action Pathway;Hydroflumethiazide Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Chlorothiazide Action Pathway;Dezocine Action Pathway;Calcium Regulation in the Cardiac Cell;oxidative stress induced gene expression via nrf2;Ion channel transport;Ion homeostasis;Transport of small molecules;Cardiac conduction;Muscle contraction;Ion transport by P-type ATPases (Consensus)

Intolerance Scores

loftool
0.281
rvis_EVS
0.19
rvis_percentile_EVS
66.82

Haploinsufficiency Scores

pHI
0.199
hipred
N
hipred_score
0.210
ghis
0.403

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.000434

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Fxyd2
Phenotype
normal phenotype;

Gene ontology

Biological process
establishment or maintenance of transmembrane electrochemical gradient;sodium ion export across plasma membrane;ATP hydrolysis coupled transmembrane transport;potassium ion import across plasma membrane;regulation of sodium ion transmembrane transporter activity
Cellular component
plasma membrane;sodium:potassium-exchanging ATPase complex;extracellular exosome
Molecular function
transporter activity;sodium:potassium-exchanging ATPase activity;sodium channel regulator activity;ion channel regulator activity