ATP1B4

Summary

ATP1B4 (ATPase Na+/K+ transporting family member beta 4, HGNC:808) is a protein-coding gene on chromosome Xq24, encoding Protein ATP1B4 (Q9UN42). May act as a transcriptional coregulator during muscle development through its interaction with SNW1.

This gene has been found in all vertebrate genomes sequenced to date. However, this gene has undergone a change in function in placental mammals compared to other species. Specifically, in fish, avian, and amphibian species, this gene encodes plasma membrane-bound beta-subunits of Na,K-ATPase. In placental mammals, the encoded protein interacts with the nuclear transcriptional coregulator SKIP and may be involved in the regulation of TGF-beta signaling. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 23439 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 76 total — 1 pathogenic
• MANE Select transcript: NM_001142447

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:808
Approved symbol	ATP1B4
Name	ATPase Na+/K+ transporting family member beta 4
Location	Xq24
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101892
Ensembl biotype	protein_coding
OMIM	301073
Entrez	23439

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000218008, ENST00000361319, ENST00000539306, ENST00000955249, ENST00000955250, ENST00000955251, ENST00000955252, ENST00000955253

RefSeq mRNA: 2 — MANE Select: NM_001142447 NM_001142447, NM_012069

CCDS: CCDS14598, CCDS48158

Canonical transcript exons

ENST00000218008 — 8 exons

Exon	Start	End
ENSE00000675744	120366525	120366789
ENSE00000675745	120370715	120370843
ENSE00000675746	120371106	120371210
ENSE00000675748	120375372	120375568
ENSE00000675749	120376380	120376436
ENSE00000675751	120378678	120378773
ENSE00003844628	120379473	120383237
ENSE00003846344	120362089	120362231

Expression profiles

Bgee: expression breadth broad, 60 present calls, max score 97.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1612 / max 233.1638, expressed in 135 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197424	1.0682	132
197423	0.0930	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.31	gold quality
biceps brachii	UBERON:0001507	95.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.88	gold quality
vastus lateralis	UBERON:0001379	89.92	gold quality
quadriceps femoris	UBERON:0001377	88.19	gold quality
skeletal muscle tissue	UBERON:0001134	87.44	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.74	gold quality
diaphragm	UBERON:0001103	84.78	silver quality
deltoid	UBERON:0001476	84.53	gold quality
skeletal muscle organ	UBERON:0014892	84.19	gold quality
muscle organ	UBERON:0001630	84.18	gold quality
gastrocnemius	UBERON:0001388	82.92	gold quality
muscle of leg	UBERON:0001383	82.40	gold quality
gluteal muscle	UBERON:0002000	82.27	gold quality
body of tongue	UBERON:0011876	81.90	gold quality
triceps brachii	UBERON:0001509	81.40	gold quality
muscle tissue	UBERON:0002385	79.29	gold quality
tibialis anterior	UBERON:0001385	77.92	silver quality
tongue	UBERON:0001723	69.74	gold quality
buccal mucosa cell	CL:0002336	69.05	silver quality
superior surface of tongue	UBERON:0007371	61.45	gold quality
tendon of biceps brachii	UBERON:0008188	59.49	gold quality
pancreatic ductal cell	CL:0002079	56.55	silver quality
decidua	UBERON:0002450	56.55	gold quality
trabecular bone tissue	UBERON:0002483	56.35	silver quality
jejunum	UBERON:0002115	55.84	gold quality
lower lobe of lung	UBERON:0008949	53.56	silver quality
hair follicle	UBERON:0002073	53.38	gold quality
synovial joint	UBERON:0002217	53.02	gold quality
ileal mucosa	UBERON:0000331	52.16	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

204 targeting ATP1B4, 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-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 1)

• variant in the coding region of the ATP1B4 gene may play little or no role in the development of PD in Chinese Han population. (PMID:24420862)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp1b4	ENSDARG00000053262
mus_musculus	Atp1b4	ENSMUSG00000016327
rattus_norvegicus	Atp1b4	ENSRNOG00000007059

Paralogs (4): ATP1B3 (ENSG00000069849), ATP1B2 (ENSG00000129244), ATP1B1 (ENSG00000143153), ATP4B (ENSG00000186009)

Protein

Protein identifiers

Protein ATP1B4 — Q9UN42 (reviewed: Q9UN42)

Alternative names: X,K-ATPase subunit beta-m, X/potassium-transporting ATPase subunit beta-m

All UniProt accessions (2): Q9UN42, B7ZKW0

UniProt curated annotations — full annotation on UniProt →

Function. May act as a transcriptional coregulator during muscle development through its interaction with SNW1. Has lost its ancestral function as a Na,K-ATPase beta-subunit.

Subunit / interactions. Associates with a SMAD7-transcriptional complex. Interacts with SNW1 and TOR1AIP1. According to PubMed:17592128, does not associate with known Na,K-ATPase alpha-subunits.

Subcellular location. Nucleus inner membrane.

Tissue specificity. Highly expressed in skeletal muscle and at a lower level in heart.

Similarity. Belongs to the X(+)/potassium ATPases subunit beta family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UN42-1	A	yes
Q9UN42-2	B

RefSeq proteins (2): NP_001135919, NP_036201 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000402	Na/K_ATPase_sub_beta	Family
IPR038702	Na/K_ATPase_sub_beta_sf	Homologous_superfamily

Pfam: PF00287

UniProt features (8 total): topological domain 2, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UN42-F1	81.54	0.54

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-162582	Signal Transduction
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 144 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, RORA1_01, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, PAX8_B, HFH8_01, FOXJ2_01, HFH4_01, HFH3_01, HFH1_01, E2F1_Q3, CCAGGGG_MIR331, FREAC7_01

GO Biological Process (5): regulation of DNA-templated transcription (GO:0006355), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), monoatomic ion transport (GO:0006811), transmembrane transport (GO:0055085)

GO Molecular Function (2): obsolete inorganic cation transmembrane transporter activity (GO:0022890), protein binding (GO:0005515)

GO Cellular Component (6): nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), plasma membrane (GO:0005886), sodium:potassium-exchanging ATPase complex (GO:0005890), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Signaling by TGFB family members	1
RNA Polymerase II Transcription	1
Signaling by TGF-beta Receptor Complex	1
Generic Transcription Pathway	1
Gene expression (Transcription)	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion transport	2
transport	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular process	1
binding	1
nucleus	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
membrane	1
cell periphery	1
cation-transporting ATPase complex	1
plasma membrane protein complex	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP1B4	ZNF275	Q9NSD4	523
ATP1B4	ATP1A2	P50993	461
ATP1B4	ATP1A4	Q13733	431
ATP1B4	OR8H1	Q8NGG4	419
ATP1B4	PIP4K2C	Q8TBX8	405
ATP1B4	ATP1A3	P13637	401
ATP1B4	OR6N1	Q8NGY5	391
ATP1B4	ATP5MK	Q96IX5	380
ATP1B4	C1orf105	O95561	370
ATP1B4	OR13F1	Q8NGS4	366
ATP1B4	ATP13A3	Q9H7F0	360
ATP1B4	ATP1A1	P05023	359
ATP1B4	TMEM255A	Q5JRV8	353
ATP1B4	GCDH	Q92947	353
ATP1B4	OR10A5	Q9H207	352

IntAct

26 interactions, top by confidence:

A	B	Type	Score
ERMP1	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
SMIM3	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
TSPAN2	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
CSGALNACT2	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
CXCL9	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
TTMP	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	ATP1B4	psi-mi:“MI:0915”(physical association)	0.560
Snw1	ATP1B4	psi-mi:“MI:0915”(physical association)	0.400
ATP1B4	SYNGR3	psi-mi:“MI:0914”(association)	0.350
ATP1B4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TTMP	ATP1B4	psi-mi:“MI:0915”(physical association)	0.000
ASGR1	ATP1B4	psi-mi:“MI:0915”(physical association)	0.000
ERMP1	ATP1B4	psi-mi:“MI:0915”(physical association)	0.000
SMIM3	ATP1B4	psi-mi:“MI:0915”(physical association)	0.000
TSPAN2	ATP1B4	psi-mi:“MI:0915”(physical association)	0.000
CSGALNACT2	ATP1B4	psi-mi:“MI:0915”(physical association)	0.000
CXCL9	ATP1B4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (92): EMC1 (Affinity Capture-MS), ATP1A4 (Affinity Capture-MS), HLA-A (Affinity Capture-MS), SCAP (Affinity Capture-MS), ITPRIP (Affinity Capture-MS), PTK7 (Affinity Capture-MS), SPPL2B (Affinity Capture-MS), POMT1 (Affinity Capture-MS), POMT2 (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), GLB1L2 (Affinity Capture-MS), PGAP1 (Affinity Capture-MS), MGRN1 (Affinity Capture-MS), TMEM67 (Affinity Capture-MS), RTN2 (Affinity Capture-MS)

ESM2 similar proteins: A7MB71, A8X4W9, F8W463, O73798, O97827, P05029, P15127, P15208, P18434, P18597, P18598, P21188, P25169, P30715, P30716, P33704, P33879, P43002, P49654, P50992, P51164, P51578, P54709, P56373, P97370, Q202B1, Q24046, Q3T0C6, Q3UR32, Q60489, Q63377, Q64663, Q6DE92, Q6UX71, Q80TS3, Q8IUK5, Q91VE2, Q93086, Q93235, Q99572

Diamond homologs: A5A6J8, A7MB71, P05026, P05027, P05028, P05029, P06583, P07340, P08251, P13638, P14094, P14231, P14415, P18434, P18597, P18598, P21188, P25169, P30715, P30716, P33704, P33879, P43002, P51165, P54709, P97370, Q202B1, Q24046, Q28030, Q2HZ96, Q3T0C6, Q4R4V5, Q5J583, Q5R8S8, Q60489, Q63377, Q8WMG3, Q99ME6, Q9BDK6, Q9GLC3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	54
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1341314	GRCh37/hg19 Xq24-25(chrX:119173583-126584360)x2	Pathogenic

SpliceAI

1693 predictions. Top by Δscore:

Variant	Effect	Δscore
X:120362227:GACTC:G	donor_gain	1.0000
X:120362232:G:GG	donor_gain	1.0000
X:120366651:G:GT	donor_gain	1.0000
X:120366657:G:GT	donor_gain	1.0000
X:120366666:G:GT	donor_gain	1.0000
X:120370746:T:G	acceptor_gain	1.0000
X:120373051:G:GT	donor_gain	1.0000
X:120378675:CAGAG:C	acceptor_gain	1.0000
X:120378676:AGAGA:A	acceptor_gain	1.0000
X:120378677:GA:G	acceptor_gain	1.0000
X:120378677:GAGA:G	acceptor_gain	1.0000
X:120378677:GAGAG:G	acceptor_gain	1.0000
X:120378774:G:GG	donor_gain	1.0000
X:120362187:TCCAG:T	donor_gain	0.9900
X:120362216:T:G	donor_gain	0.9900
X:120362228:ACTC:A	donor_gain	0.9900
X:120362228:ACTCG:A	donor_loss	0.9900
X:120362229:CTC:C	donor_gain	0.9900
X:120362229:CTCGT:C	donor_loss	0.9900
X:120362230:TC:T	donor_gain	0.9900
X:120362230:TCGT:T	donor_loss	0.9900
X:120362231:CGTGA:C	donor_loss	0.9900
X:120362232:GTGA:G	donor_loss	0.9900
X:120362233:TGAGT:T	donor_loss	0.9900
X:120362234:GAGTG:G	donor_loss	0.9900
X:120365803:C:G	donor_gain	0.9900
X:120366515:ACT:A	acceptor_gain	0.9900
X:120366517:T:A	acceptor_gain	0.9900
X:120366520:TCCAG:T	acceptor_loss	0.9900
X:120366521:CCAGG:C	acceptor_loss	0.9900

AlphaMissense

2376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:120375473:T:C	F222L	1.000
X:120375475:T:A	F222L	1.000
X:120375475:T:G	F222L	1.000
X:120379545:T:A	C329S	1.000
X:120379546:G:C	C329S	1.000
X:120371205:T:C	L186P	0.999
X:120375467:T:A	C220S	0.999
X:120375468:G:A	C220Y	0.999
X:120375468:G:C	C220S	0.999
X:120375474:T:C	F222S	0.999
X:120375474:T:G	F222C	0.999
X:120375497:T:A	C230S	0.999
X:120375498:G:A	C230Y	0.999
X:120375498:G:C	C230S	0.999
X:120375521:T:C	F238L	0.999
X:120375523:T:A	F238L	0.999
X:120375523:T:G	F238L	0.999
X:120375527:T:G	Y240D	0.999
X:120375545:T:A	C246S	0.999
X:120375545:T:C	C246R	0.999
X:120375546:G:A	C246Y	0.999
X:120375546:G:C	C246S	0.999
X:120375547:C:G	C246W	0.999
X:120376425:T:A	C269S	0.999
X:120376425:T:C	C269R	0.999
X:120376426:G:A	C269Y	0.999
X:120376426:G:C	C269S	0.999
X:120379507:T:C	F316S	0.999
X:120379545:T:C	C329R	0.999
X:120379612:T:C	F351S	0.999

dbSNP variants (sampled 300 via entrez): RS1000057342 (X:120368028 A>G), RS1000135478 (X:120376230 T>C), RS1000256260 (X:120380499 A>G), RS1000401172 (X:120373551 C>G,T), RS1000411030 (X:120373765 A>G), RS1000496999 (X:120361568 G>C,T), RS1000736303 (X:120375022 A>T), RS1000742963 (X:120375314 C>T), RS1000848189 (X:120378769 C>T), RS1000950093 (X:120367862 A>G,T), RS1000992348 (X:120382859 T>A), RS1001062133 (X:120360725 C>A), RS1001297351 (X:120367604 A>G), RS1001398379 (X:120371877 C>T), RS1001449398 (X:120372161 T>C)

Disease associations

OMIM: gene MIM:301073 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008159_55	Waist-to-hip ratio adjusted for BMI	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
sodium arsenite	affects methylation	1
2,7-dihydroxynaphthalene	decreases expression	1
incobotulinumtoxinA	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Etoposide	increases expression	1
Vanadium	decreases expression	1
Coal Ash	decreases expression	1

Clinical trials (associated diseases)

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