FXYD7

Summary

FXYD7 (FXYD domain containing ion transport regulator 7, HGNC:4034) is a protein-coding gene on chromosome 19q13.12, encoding FXYD domain-containing ion transport regulator 7 (P58549). Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane.

This reference sequence was derived from multiple replicate ESTs and validated by similar human genomic sequence. 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. 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. 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. This gene product, FXYD7, is novel and has not been characterized as a protein. [RefSeq curation by Kathleen J. Sweadner, Ph.D., [email protected]., Dec 2000]

Source: NCBI Gene 53822 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_022006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4034
Approved symbol	FXYD7
Name	FXYD domain containing ion transport regulator 7
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000221946
Ensembl biotype	protein_coding
OMIM	606684
Entrez	53822

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000270310, ENST00000439441, ENST00000586063, ENST00000588265, ENST00000900287, ENST00000934123, ENST00000968511, ENST00000968512, ENST00000968513

RefSeq mRNA: 1 — MANE Select: NM_022006 NM_022006

CCDS: CCDS12446

Canonical transcript exons

ENST00000270310 — 6 exons

Exon	Start	End
ENSE00000000087	35143255	35143364
ENSE00000953282	35151254	35151328
ENSE00000953283	35151440	35151482
ENSE00000953284	35151633	35151673
ENSE00001368793	35153894	35154302
ENSE00003627636	35148694	35148723

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 99.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2004 / max 14.3536, expressed in 117 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175234	10.8481	457
175232	0.3907	63
175233	0.2210	77
175225	0.2004	117
175235	0.0704	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	99.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.92	gold quality
superior frontal gyrus	UBERON:0002661	98.89	gold quality
amygdala	UBERON:0001876	98.76	gold quality
temporal lobe	UBERON:0001871	98.74	gold quality
anterior cingulate cortex	UBERON:0009835	98.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.60	gold quality
Ammon’s horn	UBERON:0001954	98.56	gold quality
right frontal lobe	UBERON:0002810	98.47	gold quality
putamen	UBERON:0001874	98.20	gold quality
caudate nucleus	UBERON:0001873	97.35	gold quality
nucleus accumbens	UBERON:0001882	97.17	gold quality
hypothalamus	UBERON:0001898	96.76	gold quality
substantia nigra	UBERON:0002038	96.53	gold quality
cortical plate	UBERON:0005343	92.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.35	gold quality
brain	UBERON:0000955	86.77	gold quality
tibial nerve	UBERON:0001323	86.67	gold quality
cerebral cortex	UBERON:0000956	85.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.32	gold quality
sural nerve	UBERON:0015488	84.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.94	gold quality
mucosa of stomach	UBERON:0001199	80.98	gold quality
cerebellum	UBERON:0002037	80.36	gold quality
cerebellar cortex	UBERON:0002129	80.26	gold quality
cerebellar hemisphere	UBERON:0002245	80.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.39	silver quality
granulocyte	CL:0000094	78.72	gold quality
ectocervix	UBERON:0012249	77.06	gold quality
blood	UBERON:0000178	75.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	12.33
E-GEOD-70580	no	391.46
E-ANND-3	no	3.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting FXYD7, 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-4731-5P	99.89	67.23	2537
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-6889-5P	90.26	64.13	291
HSA-MIR-542-5P	87.47	60.42	76

Literature-anchored findings (GeneRIF, showing 1)

• Intracellular trafficking of FXYD1 (phospholemman) and FXYD7 proteins in Xenopus oocytes and mammalian cells. (PMID:22535957)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fxyd7	ENSMUSG00000036578
rattus_norvegicus	Fxyd7	ENSRNOG00000021067

Paralogs (6): FXYD5 (ENSG00000089327), FXYD3 (ENSG00000089356), FXYD6 (ENSG00000137726), FXYD2 (ENSG00000137731), FXYD4 (ENSG00000150201), FXYD1 (ENSG00000266964)

Protein

Protein identifiers

FXYD domain-containing ion transport regulator 7 — P58549 (reviewed: P58549)

All UniProt accessions (3): P58549, K7EKU3, K7ENE8

UniProt curated annotations — full annotation on UniProt →

Function. Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. Reduces the apparent affinity for external K(+), an effect that depends on the presence of external Na(+) and voltage. Increases the apparent affinity for intracellular Na(+).

Subunit / interactions. Regulatory subunit of the sodium/potassium-transporting ATPase which is composed of a catalytic alpha subunit, a non-catalytic beta subunit and a FXYD regulatory unit that modulates the enzymatic activity in a tissue- and isoform-specific way by changing affinities of the Na+/K+-ATPase toward Na(+), K(+) or ATP.

Subcellular location. Cell membrane.

Post-translational modifications. O-glycosylated; required for stabilization and translocation to the plasma membrane.

Domain organisation. The transmembrane domain is important for the interaction with NKA and with the functional effect of FXYD7.

Similarity. Belongs to the FXYD family.

RefSeq proteins (1): NP_071289* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000272	Ion-transport_regulator_FXYD	Family
IPR047284	FXYD7	Family
IPR047297	FXYD_motif	Conserved_site

Pfam: PF02038

UniProt features (9 total): glycosylation site 3, topological domain 2, chain 1, transmembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58549-F1	71.62	0.29

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): 73

Glycosylation sites (3): 3, 5, 9

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: 126 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_TRANSMEMBRANE_ELECTROCHEMICAL_GRADIENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSPORT, GGGTGGRR_PAX4_03, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_INTRACELLULAR_POTASSIUM_ION_HOMEOSTASIS, GOBP_INTRACELLULAR_SODIUM_ION_HOMEOSTASIS, GOBP_POSITIVE_REGULATION_OF_SODIUM_ION_TRANSMEMBRANE_TRANSPORT

GO Biological Process (5): potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), positive regulation of sodium ion export across plasma membrane (GO:1903278), monoatomic ion transport (GO:0006811), regulation of monoatomic ion transport (GO:0043269)

GO Molecular Function (4): sodium channel regulator activity (GO:0017080), ATPase binding (GO:0051117), protein binding (GO:0005515), ion channel regulator activity (GO:0099106)

GO Cellular Component (2): plasma membrane (GO:0005886), 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
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
sodium channel activity	1
ion channel regulator activity	1
enzyme binding	1
binding	1
monoatomic ion channel activity	1
channel regulator activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FXYD7	FXYD4	P59646	829
FXYD7	ATP1B1	P05026	804
FXYD7	FXYD3	Q14802	775
FXYD7	FXYD5	Q96DB9	681
FXYD7	SYP	P08247	589
FXYD7	GFAP	P14136	542
FXYD7	FXYD2	P54710	382
FXYD7	FXYD1	O00168	358
FXYD7	VSTM2B	A6NLU5	352
FXYD7	IGFL3	Q6UXB1	322
FXYD7	FXYD6	Q9H0Q3	321
FXYD7	TAC1	P20366	314
FXYD7	CHODL	Q9H9P2	313
FXYD7	A0A087WZ82	A0A087WZ82	311
FXYD7	ECEL1	O95672	295

IntAct

18 interactions, top by confidence:

A	B	Type	Score
SGTA	FXYD7	psi-mi:“MI:0915”(physical association)	0.750
FXYD7	SGTA	psi-mi:“MI:0915”(physical association)	0.750
APPBP2	FXYD7	psi-mi:“MI:0915”(physical association)	0.720
FXYD7	APPBP2	psi-mi:“MI:0915”(physical association)	0.720
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
FXYD7	APPBP2	psi-mi:“MI:0915”(physical association)	0.000
FXYD7	SGTA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): FXYD7 (Two-hybrid), FXYD7 (Two-hybrid), FXYD7 (Two-hybrid), FXYD7 (Two-hybrid), Atp1a1 (Affinity Capture-Western), Atp1b1 (Affinity Capture-Western), FXYD7 (Two-hybrid)

ESM2 similar proteins: A0A1B0GRQ0, A0A1B0GSZ0, A0A1B0GVQ0, A0A1B0GVT2, A0JNM1, A2A9G7, A2VE22, A6NFZ4, A6NLX4, A6PVL3, A9CBA0, D3ZR35, E9Q942, O14669, O75324, P0DJ93, P58549, P59648, P59649, P61807, P61808, P86045, Q0II74, Q0VFL4, Q16655, Q17Q87, Q2KIK3, Q307W7, Q3ZBJ3, Q498C7, Q58CU5, Q5HZE8, Q5RF07, Q6UWT2, Q6UWV7, Q78HU7, Q80WK2, Q86UW2, Q8K1D8, Q8N5W8

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

677 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35143361:AAGG:A	donor_gain	1.0000
19:35143361:AAGGG:A	donor_loss	1.0000
19:35143362:AGG:A	donor_gain	1.0000
19:35143362:AGGG:A	donor_loss	1.0000
19:35143363:GG:G	donor_gain	1.0000
19:35143363:GGG:G	donor_gain	1.0000
19:35143363:GGGT:G	donor_loss	1.0000
19:35143364:G:GT	donor_gain	1.0000
19:35143364:GGTG:G	donor_loss	1.0000
19:35143365:G:C	donor_loss	1.0000
19:35143365:G:GG	donor_gain	1.0000
19:35143366:T:G	donor_loss	1.0000
19:35151329:G:GG	donor_gain	1.0000
19:35143360:AAAGG:A	donor_gain	0.9900
19:35148678:T:TA	acceptor_gain	0.9900
19:35151248:CCCCA:C	acceptor_loss	0.9900
19:35151249:CCCA:C	acceptor_loss	0.9900
19:35151251:CAGA:C	acceptor_loss	0.9900
19:35151252:A:AG	acceptor_gain	0.9900
19:35151252:A:G	acceptor_loss	0.9900
19:35151253:G:GA	acceptor_gain	0.9900
19:35151253:GA:G	acceptor_gain	0.9900
19:35151326:TCA:T	donor_gain	0.9900
19:35151326:TCAGT:T	donor_loss	0.9900
19:35151327:CA:C	donor_gain	0.9900
19:35151328:AGTAA:A	donor_loss	0.9900
19:35151329:G:C	donor_loss	0.9900
19:35151330:TAAG:T	donor_loss	0.9900
19:35151331:A:AG	donor_loss	0.9900
19:35151494:G:GG	donor_gain	0.9900

AlphaMissense

510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35151310:G:C	G40R	0.998
19:35151290:C:A	A33E	0.995
19:35151278:G:A	G29D	0.994
19:35151311:G:A	G40D	0.994
19:35151277:G:C	G29R	0.992
19:35148714:T:C	F18L	0.990
19:35148716:T:A	F18L	0.990
19:35148716:T:G	F18L	0.990
19:35151454:T:A	C51S	0.990
19:35151455:G:C	C51S	0.990
19:35151323:T:A	V44D	0.987
19:35151266:T:A	V25E	0.986
19:35148715:T:G	F18C	0.985
19:35151454:T:C	C51R	0.985
19:35151287:T:G	L32R	0.984
19:35151289:G:C	A33P	0.981
19:35151301:T:C	F37L	0.980
19:35151303:C:A	F37L	0.980
19:35151303:C:G	F37L	0.980
19:35151287:T:C	L32P	0.978
19:35151305:T:G	L38R	0.978
19:35151269:A:C	Q26P	0.977
19:35151254:A:T	D21V	0.976
19:35151456:C:G	C51W	0.974
19:35151254:A:C	D21A	0.969
19:35151277:G:T	G29C	0.969
19:35151278:G:T	G29V	0.969
19:35148715:T:C	F18S	0.967
19:35151455:G:A	C51Y	0.967
19:35151287:T:A	L32Q	0.966

dbSNP variants (sampled 300 via entrez): RS1000057707 (19:35150553 G>T), RS1000139815 (19:35144307 C>G), RS1000146135 (19:35151042 G>C), RS1000279557 (19:35144570 C>G), RS1000958259 (19:35145360 G>A,C), RS1001174362 (19:35149515 T>A), RS1001182405 (19:35149985 C>T), RS1001263775 (19:35143907 A>G), RS1001330308 (19:35145188 C>A,T), RS1001695244 (19:35144238 G>A), RS1001820342 (19:35149708 A>C,G), RS1002054547 (19:35145523 G>C), RS1002062648 (19:35154390 G>A), RS1002392251 (19:35154068 G>A,C), RS1002736826 (19:35142857 G>A)

Disease associations

OMIM: gene MIM:606684 | 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)

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Fonofos	increases methylation	1
Estradiol	increases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA46	IDG-HEK293T-FXYD7-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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