NKAIN1

Summary

NKAIN1 (sodium/potassium transporting ATPase interacting 1, HGNC:25743) is a protein-coding gene on chromosome 1p35.2, encoding Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 (Q4KMZ8).

NKAIN1 is a member of a family of mammalian proteins 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 79570 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_024522

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25743
Approved symbol	NKAIN1
Name	sodium/potassium transporting ATPase interacting 1
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12650
Ensembl gene	ENSG00000084628
Ensembl biotype	protein_coding
OMIM	612871
Entrez	79570

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000373736, ENST00000526106, ENST00000528449, ENST00000530145, ENST00000533581, ENST00000916251, ENST00000916252, ENST00000916253, ENST00000950368

RefSeq mRNA: 1 — MANE Select: NM_024522 NM_024522

CCDS: CCDS339

Canonical transcript exons

ENST00000373736 — 7 exons

Exon	Start	End
ENSE00000825219	31181860	31181941
ENSE00000825220	31182530	31182590
ENSE00001461420	31179745	31181712
ENSE00001461423	31239494	31239887
ENSE00003371103	31185247	31185327
ENSE00003442650	31183817	31184014
ENSE00003590634	31188050	31188187

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 98.13.

FANTOM5 (CAGE): breadth broad, TPM avg 4.0802 / max 183.6549, expressed in 502 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11453	2.0604	419
11454	1.8205	380
11450	0.1009	43
11452	0.0985	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.13	gold quality
ganglionic eminence	UBERON:0004023	97.35	gold quality
cerebellar hemisphere	UBERON:0002245	88.62	gold quality
cerebellar cortex	UBERON:0002129	88.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.56	gold quality
cerebellum	UBERON:0002037	87.36	gold quality
embryo	UBERON:0000922	85.11	gold quality
ventricular zone	UBERON:0003053	83.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.18	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.75	gold quality
gastrocnemius	UBERON:0001388	80.19	gold quality
endothelial cell	CL:0000115	80.17	silver quality
muscle of leg	UBERON:0001383	79.33	gold quality
right adrenal gland cortex	UBERON:0035827	79.29	gold quality
left adrenal gland cortex	UBERON:0035825	78.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.79	gold quality
adrenal cortex	UBERON:0001235	77.67	gold quality
left adrenal gland	UBERON:0001234	77.46	gold quality
right frontal lobe	UBERON:0002810	77.23	gold quality
muscle organ	UBERON:0001630	77.08	gold quality
adrenal tissue	UBERON:0018303	75.92	gold quality
adrenal gland	UBERON:0002369	75.75	gold quality
right adrenal gland	UBERON:0001233	75.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.44	gold quality
pancreatic ductal cell	CL:0002079	75.30	silver quality
prefrontal cortex	UBERON:0000451	74.29	gold quality
cerebellar vermis	UBERON:0004720	72.90	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	72.86	gold quality
frontal cortex	UBERON:0001870	72.77	gold quality
neocortex	UBERON:0001950	72.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting NKAIN1, 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-574-5P	100.00	66.01	989
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611

Literature-anchored findings (GeneRIF, showing 2)

• NKAIN1-SERINC2 gene expression is associated with alcohol dependence in subjects of European descent. (PMID:23455491)
• NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis. (PMID:38651944)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkain1	ENSDARG00000006859
mus_musculus	Nkain1	ENSMUSG00000078532
rattus_norvegicus	Nkain1	ENSRNOG00000011445
drosophila_melanogaster	NKAIN	FBGN0085442
caenorhabditis_elegans		WBGENE00011760

Paralogs (3): NKAIN4 (ENSG00000101198), NKAIN3 (ENSG00000185942), NKAIN2 (ENSG00000188580)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 1 — Q4KMZ8 (reviewed: Q4KMZ8)

Alternative names: Protein FAM77C

All UniProt accessions (3): Q4KMZ8, H0YDA0, R4GNE2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with ATP1B1 C-terminus.

Subcellular location. Cell membrane.

Similarity. Belongs to the NKAIN family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q4KMZ8-1	1	yes
Q4KMZ8-3	2

RefSeq proteins (1): NP_078798* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008516	Na/K-Atpase_Interacting	Family

Pfam: PF05640

UniProt features (13 total): topological domain 4, transmembrane region 3, splice variant 2, signal peptide 1, chain 1, sequence conflict 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4KMZ8-F1	75.75	0.38

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 100

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): AAGCAAT_MIR137, ACTGCAG_MIR173P, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, SMID_BREAST_CANCER_LUMINAL_B_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, RYTTCCTG_ETS2_B, ELK1_01, GOBP_REGULATION_OF_TRANSPORT, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, XU_GH1_EXOGENOUS_TARGETS_UP, GOBP_SODIUM_ION_TRANSPORT, chr1p35, GOMF_ATPASE_BINDING

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

GO Molecular Function (1): ATPase binding (GO:0051117)

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
enzyme binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKAIN1	ATP1B1	P05026	911
NKAIN1	RBFOX3	A6NFN3	810
NKAIN1	PXK	Q7Z7A4	693
NKAIN1	SERINC2	Q96SA4	514
NKAIN1	SENP6	Q9GZR1	496
NKAIN1	GRIP2	Q9C0E4	489
NKAIN1	ZCCHC17	Q9NP64	467
NKAIN1	SNRNP40	Q96DI7	453
NKAIN1	SLC25A4	P12235	424
NKAIN1	TMEM169	Q96HH4	397
NKAIN1	DLK2	Q6UY11	393
NKAIN1	SDR16C5	Q8N3Y7	382
NKAIN1	IGFL1	Q6UW32	370
NKAIN1	MANEA	Q5SRI9	367
NKAIN1	Q3KRG4	Q3KRG4	359

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NKAIN1	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): C1orf43 (Affinity Capture-MS), EPHX1 (Affinity Capture-MS), MBTPS2 (Affinity Capture-MS), TUSC3 (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS), ADCY6 (Affinity Capture-MS), SLC4A2 (Affinity Capture-MS), BTN2A2 (Affinity Capture-MS), FZD6 (Affinity Capture-MS), LPAR3 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), PIGO (Affinity Capture-MS), LRRC8D (Affinity Capture-MS), GPR89A (Affinity Capture-MS), GJA1 (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2016 predictions. Top by Δscore:

Variant	Effect	Δscore
1:31181710:GACC:G	acceptor_loss	1.0000
1:31181858:A:AC	donor_gain	1.0000
1:31181859:C:CC	donor_gain	1.0000
1:31181864:A:AC	donor_gain	1.0000
1:31181865:C:CC	donor_gain	1.0000
1:31181876:G:C	donor_gain	1.0000
1:31181938:TCAA:T	acceptor_gain	1.0000
1:31181939:CAA:C	acceptor_gain	1.0000
1:31181939:CAAC:C	acceptor_gain	1.0000
1:31181940:AA:A	acceptor_gain	1.0000
1:31181941:AC:A	acceptor_loss	1.0000
1:31181942:C:CC	acceptor_gain	1.0000
1:31181942:C:T	acceptor_loss	1.0000
1:31181943:T:A	acceptor_loss	1.0000
1:31182524:A:AC	donor_gain	1.0000
1:31182525:C:CC	donor_gain	1.0000
1:31182525:CT:C	donor_gain	1.0000
1:31182525:CTCA:C	donor_gain	1.0000
1:31182526:TCACA:T	donor_loss	1.0000
1:31182527:CACA:C	donor_loss	1.0000
1:31182528:A:AC	donor_gain	1.0000
1:31182529:C:CC	donor_gain	1.0000
1:31182529:CAG:C	donor_gain	1.0000
1:31182588:CAG:C	acceptor_gain	1.0000
1:31182591:C:CC	acceptor_gain	1.0000
1:31183814:TA:T	donor_loss	1.0000
1:31183815:A:AC	donor_gain	1.0000
1:31183815:AC:A	donor_loss	1.0000
1:31183815:ACTG:A	donor_gain	1.0000
1:31183815:ACTGC:A	donor_gain	1.0000

AlphaMissense

1343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:31183875:C:G	C138S	0.999
1:31183876:A:T	C138S	0.999
1:31183943:G:C	C115W	0.999
1:31183944:C:G	C115S	0.999
1:31183945:A:G	C115R	0.999
1:31183945:A:T	C115S	0.999
1:31183964:C:A	W108C	0.999
1:31183964:C:G	W108C	0.999
1:31183966:A:G	W108R	0.999
1:31183966:A:T	W108R	0.999
1:31183967:C:A	W107C	0.999
1:31183967:C:G	W107C	0.999
1:31183969:A:G	W107R	0.999
1:31183969:A:T	W107R	0.999
1:31185292:A:C	N76K	0.999
1:31185292:A:T	N76K	0.999
1:31185297:A:G	W75R	0.999
1:31185297:A:T	W75R	0.999
1:31188140:C:A	W34C	0.999
1:31188140:C:G	W34C	0.999
1:31188142:A:G	W34R	0.999
1:31188142:A:T	W34R	0.999
1:31183838:G:C	S150R	0.998
1:31183838:G:T	S150R	0.998
1:31183840:T:G	S150R	0.998
1:31183874:G:C	C138W	0.998
1:31183876:A:G	C138R	0.998
1:31183944:C:A	C115F	0.998
1:31183944:C:T	C115Y	0.998
1:31183971:G:A	S106F	0.998

dbSNP variants (sampled 300 via entrez): RS1000064271 (1:31205045 A>G,T), RS1000112137 (1:31241200 C>T), RS1000140596 (1:31219900 G>A), RS1000262796 (1:31200089 G>A), RS1000303693 (1:31222623 C>T), RS1000338472 (1:31199478 C>T), RS1000349649 (1:31234600 A>G), RS1000461717 (1:31187687 G>A), RS1000560017 (1:31211886 G>A), RS1000612305 (1:31212090 A>T), RS1000715733 (1:31211310 T>G), RS1000742643 (1:31221480 G>A,T), RS1000749282 (1:31215837 T>C), RS1000794939 (1:31230150 C>T), RS1000851220 (1:31189198 C>G,T)

Disease associations

OMIM: gene MIM:612871 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001874_1	Alcohol dependence	3.000000e-08
GCST005769_2	Body mass index	9.000000e-06
GCST005951_36	Body mass index	9.000000e-10
GCST90020026_537	Hip index	1.000000e-12
GCST90020028_525	Hip circumference adjusted for BMI	5.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Valproic Acid	affects expression, decreases expression, increases methylation	3
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Aflatoxin B1	increases methylation	2
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Cyclophosphamide	affects cotreatment, affects response to substance	1
Doxorubicin	affects cotreatment, affects response to substance	1
Estradiol	increases expression	1
Fluorouracil	affects cotreatment, affects response to substance	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Smoke	increases expression	1
Paclitaxel	affects cotreatment, affects response to substance	1
Sodium Selenite	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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