FXYD2

FXYD domain containing ion transport regulator 2

Basic information

Region (hg38): 11:117800843-117828698

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

Links

ENSG00000137731 ∙ NCBI:486 ∙ OMIM:601814 ∙ HGNC:4026 ∙ Uniprot:P54710 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypomagnesemia 2, renal	AD	Renal	Surveillance for and treatment of electrolyte abnormalities can be beneficial (eg, to avoid sequelae such as pseudogout, as has been described in affected individuals)	Renal	3298795; 11062458

ClinVar

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

• not provided (58 variants)
• Renal hypomagnesemia 2 (26 variants)
• not specified (3 variants)
• Inborn genetic diseases (3 variants)
• Renal Hypomagnesemia, Dominant (2 variants)
• FXYD2-related condition (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	10	3	14
missense	1		6	2		9
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			6	3	1	10
non coding			3	9	21	33
Total	1	0	11	21	24

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)
11-117820191-G-A		Renal Hypomagnesemia, Dominant	Uncertain significance (Jun 14, 2016)
11-117820203-A-C		Renal hypomagnesemia 2	Benign (Jan 13, 2018)
11-117820230-T-C		Renal hypomagnesemia 2	Uncertain significance (Jan 13, 2018)
11-117820255-A-T		Renal hypomagnesemia 2	Uncertain significance (Jan 13, 2018)
11-117820274-G-A		Renal hypomagnesemia 2	Benign (Jan 12, 2018)
11-117820301-G-T		Renal hypomagnesemia 2	Benign (Jan 13, 2018)
11-117820308-C-T		Renal hypomagnesemia 2	Benign (Jan 13, 2018)
11-117820430-C-T			Benign (Nov 11, 2018)
11-117820433-C-T			Benign (Nov 11, 2018)
11-117820548-C-A			Likely benign (Nov 08, 2020)
11-117820637-C-T			Benign (May 24, 2021)
11-117820660-G-T		Renal hypomagnesemia 2 • not specified	Benign/Likely benign (Nov 22, 2019)
11-117820665-C-G		FXYD2-related disorder	Likely benign (Aug 24, 2020)
11-117820666-C-A		FXYD2-related disorder	Likely benign (Dec 20, 2022)
11-117820671-G-A		Renal hypomagnesemia 2	Benign (Nov 26, 2019)
11-117820675-C-A		Renal hypomagnesemia 2	Benign/Likely benign (Oct 10, 2022)
11-117820675-C-T		Renal hypomagnesemia 2	Likely benign (Mar 18, 2022)
11-117820678-C-T		Renal hypomagnesemia 2	Benign (Jan 16, 2024)
11-117820681-A-G		FXYD6-FXYD2-related disorder	Likely benign (Aug 09, 2022)
11-117820686-C-T			Uncertain significance (Jun 26, 2023)
11-117820688-T-C		not specified	Uncertain significance (Dec 20, 2023)
11-117820690-G-A		Renal hypomagnesemia 2	Benign/Likely benign (May 12, 2023)
11-117820702-G-A			Likely benign (Nov 10, 2023)
11-117820702-G-T			Likely benign (Nov 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FXYD2	protein_coding	protein_coding	ENST00000292079	5	27855

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.114	0.787	125469	0	2	125471	0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.156	49	46.0	1.06	0.00000312	426
Missense in Polyphen		20	17.963	1.1134		185
Synonymous	-0.977	23	17.8	1.29	0.00000130	114
Loss of Function	1.30	2	5.21	0.384	2.21e-7	67

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000654
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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