NKAIN4

Summary

NKAIN4 (sodium/potassium transporting ATPase interacting 4, HGNC:16191) is a protein-coding gene on chromosome 20q13.33, encoding Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 4 (Q8IVV8).

NKAIN4 is a member of a family of mammalian proteins (see NKAIN1; MIM 612871) with similarity to Drosophila Nkain and interacts with the beta subunit of Na,K-ATPase (ATP1B1; MIM 182330) (Gorokhova et al., 2007 [PubMed 17606467]).

Source: NCBI Gene 128414 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_152864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16191
Approved symbol	NKAIN4
Name	sodium/potassium transporting ATPase interacting 4
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	bA261N11.2, FAM77A
Ensembl gene	ENSG00000101198
Ensembl biotype	protein_coding
OMIM	612873
Entrez	128414

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000370307, ENST00000370313, ENST00000370316, ENST00000370317, ENST00000461738, ENST00000466885, ENST00000470246, ENST00000472670, ENST00000486495

RefSeq mRNA: 3 — MANE Select: NM_152864 NM_001363718, NM_001363747, NM_152864

CCDS: CCDS13514, CCDS86967, CCDS86968

Canonical transcript exons

ENST00000370316 — 7 exons

Exon	Start	End
ENSE00001837307	63254397	63254463
ENSE00003466466	63242539	63242623
ENSE00003469479	63247578	63247775
ENSE00003493300	63249935	63250072
ENSE00003569280	63248815	63248895
ENSE00003597170	63240784	63241506
ENSE00003612624	63244024	63244084

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 95.02.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9057 / max 57.9344, expressed in 298 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188333	1.5141	283
188334	0.3698	188
188331	0.0137	4
188332	0.0062	1
188328	0.0020	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	95.02	gold quality
amygdala	UBERON:0001876	95.00	gold quality
putamen	UBERON:0001874	93.67	gold quality
hypothalamus	UBERON:0001898	93.31	gold quality
caudate nucleus	UBERON:0001873	93.13	gold quality
anterior cingulate cortex	UBERON:0009835	91.72	gold quality
substantia nigra	UBERON:0002038	91.62	gold quality
adrenal tissue	UBERON:0018303	91.33	gold quality
midbrain	UBERON:0001891	90.57	gold quality
temporal lobe	UBERON:0001871	89.42	gold quality
Ammon’s horn	UBERON:0001954	88.83	gold quality
ganglionic eminence	UBERON:0004023	88.43	gold quality
right frontal lobe	UBERON:0002810	88.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.57	gold quality
ventricular zone	UBERON:0003053	87.17	gold quality
kidney epithelium	UBERON:0004819	87.14	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.57	gold quality
spinal cord	UBERON:0002240	86.49	gold quality
ventral tegmental area	UBERON:0002691	86.34	gold quality
sural nerve	UBERON:0015488	86.04	gold quality
forebrain	UBERON:0001890	85.89	gold quality
adult mammalian kidney	UBERON:0000082	85.47	gold quality
brain	UBERON:0000955	85.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.10	gold quality
cerebral cortex	UBERON:0000956	85.06	gold quality
neocortex	UBERON:0001950	84.54	gold quality
metanephros cortex	UBERON:0010533	84.45	gold quality
prefrontal cortex	UBERON:0000451	84.29	gold quality
dorsal root ganglion	UBERON:0000044	84.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	306.05
E-GEOD-84465	yes	24.36
E-ANND-3	yes	4.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting NKAIN4, 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-627-3P	99.90	71.42	3316
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-744-3P	97.99	67.76	637
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkain4	ENSDARG00000062699
mus_musculus	Nkain4	ENSMUSG00000027574
rattus_norvegicus	Nkain4	ENSRNOG00000031834
drosophila_melanogaster	NKAIN	FBGN0085442
caenorhabditis_elegans		WBGENE00011760

Paralogs (3): NKAIN1 (ENSG00000084628), NKAIN3 (ENSG00000185942), NKAIN2 (ENSG00000188580)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 4 — Q8IVV8 (reviewed: Q8IVV8)

Alternative names: Protein FAM77A

All UniProt accessions (4): Q8IVV8, A6NNM2, J3JS66, J9JIE8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with ATP1B1.

Subcellular location. Cell membrane.

Similarity. Belongs to the NKAIN family.

RefSeq proteins (3): NP_001350647, NP_001350676, NP_690603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008516	Na/K-Atpase_Interacting	Family

Pfam: PF05640

UniProt features (8 total): sequence variant 4, transmembrane region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVV8-F1	71.39	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): AREB6_03, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, MYOD_Q6, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, LEIN_CEREBELLUM_MARKERS, NIKOLSKY_BREAST_CANCER_20Q12_Q13_AMPLICON, HATADA_METHYLATED_IN_LUNG_CANCER_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, CBX5_TARGET_GENES, CEBPZ_TARGET_GENES, GREB1_TARGET_GENES

GO Biological Process (1): regulation of sodium ion transport (GO:0002028)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sodium ion transport	1
regulation of metal ion transport	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKAIN4	ATP1B1	P05026	821
NKAIN4	AMZ1	Q400G9	493
NKAIN4	CMYA5	Q8N3K9	493
NKAIN4	CCDC57	Q2TAC2	474
NKAIN4	FASTKD3	Q14CZ7	466
NKAIN4	DNAJC12	Q9UKB3	459
NKAIN4	DMRT3	Q9NQL9	456
NKAIN4	RDM1	Q8NG50	452
NKAIN4	LRRN4	Q8WUT4	447
NKAIN4	FAM111A	Q96PZ2	447
NKAIN4	STK31	Q9BXU1	446
NKAIN4	FREM2	Q5SZK8	425
NKAIN4	OR6T1	Q8NGN1	418
NKAIN4	MESP2	Q0VG99	418
NKAIN4	RASAL1	O95294	418

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MAL	NKAIN4	psi-mi:“MI:0915”(physical association)	0.560
NKAIN4	ENDOD1	psi-mi:“MI:0914”(association)	0.350
MAL	NKAIN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): MAL (Two-hybrid), NKAIN4 (Negative Genetic), CAV2 (Affinity Capture-MS), ENDOD1 (Affinity Capture-MS)

ESM2 similar proteins: A2VE61, A6QNL6, Q0IHU6, Q0VFK3, Q17QL9, Q17R16, Q2YDG0, Q32NX4, Q3KRC4, Q3URJ8, Q401C0, Q4KMZ8, Q4PNJ2, Q5BL21, Q5R7B1, Q5R9I4, Q5RET6, Q5U4E0, Q5VXU1, Q5ZMP3, Q61088, Q66IV3, Q66KY5, Q68EY2, Q6DD32, Q6DEX3, Q6DHB5, Q6NYY9, Q6P360, Q6PHL4, Q7TSY2, Q7Z7J7, Q810F1, Q86UP9, Q8BXA5, Q8IVV8, Q8IWA5, Q8K3J9, Q8N8D7, Q8WVP7

Diamond homologs: A6MHQ4, A6QNL6, Q0IHU6, Q0VFH9, Q32NX4, Q3URJ8, Q4KMZ8, Q4PNJ2, Q5VXU1, Q66KY5, Q66KZ9, Q6DEX3, Q6PHL4, Q8IVV8, Q8N8D7, Q9D035, Q9JMG4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1495 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63247572:GCTCA:G	donor_loss	1.0000
20:63247573:CTCA:C	donor_loss	1.0000
20:63247574:TCA:T	donor_loss	1.0000
20:63247575:CA:C	donor_loss	1.0000
20:63247576:A:AC	donor_gain	1.0000
20:63247577:C:CC	donor_gain	1.0000
20:63247577:C:CT	donor_loss	1.0000
20:63247577:CCG:C	donor_gain	1.0000
20:63247771:CTGTC:C	acceptor_gain	1.0000
20:63247772:TGTCC:T	acceptor_loss	1.0000
20:63247777:T:G	acceptor_loss	1.0000
20:63248810:CTCA:C	donor_loss	1.0000
20:63248811:TCACC:T	donor_loss	1.0000
20:63248812:CACCT:C	donor_loss	1.0000
20:63248813:A:AC	donor_gain	1.0000
20:63248813:AC:A	donor_gain	1.0000
20:63248814:C:CC	donor_gain	1.0000
20:63248814:C:CG	donor_loss	1.0000
20:63248814:CC:C	donor_gain	1.0000
20:63248891:GTGTA:G	acceptor_gain	1.0000
20:63248892:TGTA:T	acceptor_gain	1.0000
20:63248893:GTA:G	acceptor_gain	1.0000
20:63248893:GTAC:G	acceptor_loss	1.0000
20:63248894:TA:T	acceptor_gain	1.0000
20:63248894:TAC:T	acceptor_loss	1.0000
20:63248895:AC:A	acceptor_loss	1.0000
20:63248896:C:CA	acceptor_loss	1.0000
20:63248896:C:CC	acceptor_gain	1.0000
20:63248897:T:G	acceptor_loss	1.0000
20:63249933:ACCAC:A	donor_gain	1.0000

AlphaMissense

1342 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63248860:G:C	N76K	0.899
20:63248860:G:T	N76K	0.899
20:63247599:A:C	S150R	0.884
20:63247599:A:T	S150R	0.884
20:63247601:T:G	S150R	0.884
20:63248865:A:G	W75R	0.867
20:63248865:A:T	W75R	0.867
20:63248886:A:G	W68R	0.852
20:63248886:A:T	W68R	0.852
20:63250040:G:C	F29L	0.836
20:63250040:G:T	F29L	0.836
20:63250042:A:G	F29L	0.836
20:63242616:G:C	F180L	0.830
20:63242616:G:T	F180L	0.830
20:63242618:A:G	F180L	0.830
20:63247755:G:C	F98L	0.826
20:63247755:G:T	F98L	0.826
20:63247757:A:G	F98L	0.826
20:63249971:G:C	F52L	0.824
20:63249971:G:T	F52L	0.824
20:63249973:A:G	F52L	0.824
20:63250025:C:A	W34C	0.815
20:63250025:C:G	W34C	0.815
20:63250055:C:A	R24S	0.815
20:63250055:C:G	R24S	0.815
20:63250007:G:C	N40K	0.795
20:63250007:G:T	N40K	0.795
20:63242622:A:C	F178L	0.790
20:63242622:A:T	F178L	0.790
20:63244024:A:G	F178L	0.790

dbSNP variants (sampled 300 via entrez): RS1000103456 (20:63245842 A>G), RS1000134541 (20:63245661 C>A,T), RS1000155526 (20:63253750 C>A), RS1000180622 (20:63256541 T>G), RS1000267582 (20:63255373 G>A), RS1000313409 (20:63249201 C>T), RS1000428627 (20:63251062 G>A), RS1000492247 (20:63252703 A>C), RS1000615464 (20:63248582 T>C), RS1000686783 (20:63249399 G>A), RS1000692981 (20:63251696 T>C), RS1000764867 (20:63252371 G>A), RS1001135973 (20:63243650 GT>G), RS1001257150 (20:63245390 C>A), RS1001473942 (20:63249092 C>G,T)

Disease associations

OMIM: gene MIM:612873 | 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

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	6
trichostatin A	affects cotreatment, decreases expression	3
Vorinostat	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Oxygen	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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