NKAIN2

Summary

NKAIN2 (sodium/potassium transporting ATPase interacting 2, HGNC:16443) is a protein-coding gene on chromosome 6q22.31, encoding Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 (Q5VXU1).

This gene encodes a transmembrane protein that interacts with the beta subunit of a sodium/potassium-transporting ATPase. A chromosomal translocation involving this gene is a cause of lymphoma. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 154215 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 40 total — 1 pathogenic
• MANE Select transcript: NM_001040214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16443
Approved symbol	NKAIN2
Name	sodium/potassium transporting ATPase interacting 2
Location	6q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FAM77B
Ensembl gene	ENSG00000188580
Ensembl biotype	protein_coding
OMIM	609758
Entrez	154215

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000368416, ENST00000368417, ENST00000476571, ENST00000640160

RefSeq mRNA: 5 — MANE Select: NM_001040214 NM_001040214, NM_001300737, NM_001300738, NM_001300740, NM_153355

CCDS: CCDS34526

Canonical transcript exons

ENST00000368417 — 7 exons

Exon	Start	End
ENSE00001368038	124658186	124658386
ENSE00001414970	124791339	124791399
ENSE00001447079	124823220	124825640
ENSE00001447080	124818387	124818468
ENSE00003502488	124283005	124283142
ENSE00003522129	124355267	124355347
ENSE00003891303	123803865	123804254

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 96.83.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9043 / max 868.3864, expressed in 329 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69590	1.6484	171
69583	0.7150	155
69589	0.6696	119
69586	0.4726	115
69585	0.4445	111
69610	0.2723	62
69588	0.2669	96
69587	0.1330	67
69584	0.1012	64
69611	0.0998	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	96.83	gold quality
spinal cord	UBERON:0002240	96.79	gold quality
corpus callosum	UBERON:0002336	96.46	gold quality
cortical plate	UBERON:0005343	95.98	gold quality
inferior vagus X ganglion	UBERON:0005363	95.81	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.06	gold quality
medulla oblongata	UBERON:0001896	94.25	gold quality
subthalamic nucleus	UBERON:0001906	93.79	gold quality
pons	UBERON:0000988	92.85	gold quality
superior vestibular nucleus	UBERON:0007227	92.22	gold quality
Ammon’s horn	UBERON:0001954	91.84	gold quality
substantia nigra	UBERON:0002038	91.80	gold quality
prefrontal cortex	UBERON:0000451	91.77	gold quality
midbrain	UBERON:0001891	91.77	gold quality
trigeminal ganglion	UBERON:0001675	91.62	gold quality
endothelial cell	CL:0000115	91.14	gold quality
medial globus pallidus	UBERON:0002477	91.10	gold quality
globus pallidus	UBERON:0001875	90.61	gold quality
dorsal root ganglion	UBERON:0000044	90.29	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.29	gold quality
amygdala	UBERON:0001876	90.28	gold quality
entorhinal cortex	UBERON:0002728	90.22	gold quality
temporal lobe	UBERON:0001871	89.98	gold quality
substantia nigra pars reticulata	UBERON:0001966	89.84	gold quality
ventral tegmental area	UBERON:0002691	89.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.15	gold quality
cerebral cortex	UBERON:0000956	89.06	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.96	gold quality
frontal cortex	UBERON:0001870	88.48	gold quality
neocortex	UBERON:0001950	88.24	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	239.02
E-HCAD-35	yes	85.18
E-HCAD-25	yes	52.66
E-ANND-3	yes	5.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

181 targeting NKAIN2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
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-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3910	99.95	71.13	2227

Literature-anchored findings (GeneRIF, showing 5)

• T-cell lymphoma breakpoint associated target 1 is a possible target gene for T-cell lineage-specific chromosome aberrations at 6q21. (PMID:11979551)
• It is concluded that germline alterations of the TCBA1 gene are associated with developmental delay and typical physical features. (PMID:15908570)
• High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines. (PMID:24205241)
• NKAIN2 is a novel tumor suppressor gene whose activity is commonly reduced in prostate cancer (PMID:27588475)
• Inhibiting miR-181d may suppress pancreatic cancer development, possibly through the inverse regulation on NKAIN2. (PMID:28381166)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkain2	ENSDARG00000069427
mus_musculus	Nkain2	ENSMUSG00000069670
rattus_norvegicus	Nkain2	ENSRNOG00000029608
drosophila_melanogaster	NKAIN	FBGN0085442
caenorhabditis_elegans		WBGENE00011760

Paralogs (3): NKAIN1 (ENSG00000084628), NKAIN4 (ENSG00000101198), NKAIN3 (ENSG00000185942)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2 — Q5VXU1 (reviewed: Q5VXU1)

Alternative names: Protein FAM77B, T-cell lymphoma breakpoint-associated target protein 1

All UniProt accessions (2): A0A1W2PRU3, Q5VXU1

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with ATP1B1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in fetal brain. Weakly expressed in adult brain and thymus. Not expressed in any other normal tissue examined.

Disease relevance. A chromosomal aberration involving NKAIN2 is a cause of lymphoma. Deletion del(6)(q13q21) within NKAIN2 and involving SUSP1 generates the SUSP1-NKAIN2 product.

Similarity. Belongs to the NKAIN family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VXU1-1	1	yes
Q5VXU1-2	2
Q5VXU1-3	3

RefSeq proteins (5): NP_001035304, NP_001287666, NP_001287667, NP_001287669, NP_699186 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008516	Na/K-Atpase_Interacting	Family

Pfam: PF05640

UniProt features (8 total): transmembrane region 4, splice variant 2, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VXU1-F1	76.15	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.

Catalytic / active sites (1): 91–92 (breakpoint for interstitial deletion to form susp1-nkain2)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 118 (showing top): BENPORATH_ES_WITH_H3K27ME3, GCANCTGNY_MYOD_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, MYOD_Q6, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, TAATGTG_MIR323, E12_Q6, GGTGAAG_MIR412, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, TGCCTTA_MIR124A, GOBP_SODIUM_ION_TRANSPORT, E2A_Q2

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

GO Molecular Function (0):

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
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKAIN2	SENP6	Q9GZR1	911
NKAIN2	ATP1B1	P05026	754
NKAIN2	SLC25A4	P12235	720
NKAIN2	PRTN3	P15637	550
NKAIN2	SENP7	Q9BQF6	549
NKAIN2	ENTPD2	Q9Y5L3	430
NKAIN2	NEUROD6	Q96NK8	419
NKAIN2	SORCS3	Q9UPU3	401
NKAIN2	AIG1	Q9NVV5	395
NKAIN2	GYG1	P46976	376
NKAIN2	OR5M10	Q6IEU7	374
NKAIN2	OR1A2	Q9Y585	373
NKAIN2	DSCAML1	Q8TD84	370
NKAIN2	DAB2	P98082	369
NKAIN2	PTPRD	P23468	365

IntAct

0 interactions, top by confidence:

BioGRID (1): NKAIN2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I3S9V6, A2BIE7, A2VE61, A6NH52, A6QNL6, Q0VCK9, Q0VFK3, Q0X0A5, Q13507, Q17R16, Q29S14, Q3KNM2, Q3KRC4, Q3ZC24, Q401C0, Q4VBD2, Q5EAY8, Q5R7B1, Q5R9I4, Q5U4E0, Q5VXU1, Q5ZJ41, Q5ZLG8, Q5ZMP3, Q68EY2, Q6DD32, Q6GM44, Q6NXT6, Q6P360, Q7TSY2, Q7Z7J7, Q8BXA5, Q8C1E7, Q8K3J9, Q8MK44, Q8R1Z9, Q91ZQ0, Q940S0, Q96GC9, Q96KA5

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58444	GRCh38/hg38 6q22.31(chr6:124116341-124499647)x1	Pathogenic

SpliceAI

4097 predictions. Top by Δscore:

Variant	Effect	Δscore
6:123835623:A:AG	donor_gain	1.0000
6:123835623:A:G	donor_gain	1.0000
6:123998409:T:TA	acceptor_gain	1.0000
6:124283004:GGTTT:G	acceptor_gain	1.0000
6:124283138:CAGGA:C	donor_gain	1.0000
6:124283139:AGGA:A	donor_gain	1.0000
6:124283140:GGA:G	donor_gain	1.0000
6:124283140:GGAG:G	donor_gain	1.0000
6:124283141:GA:G	donor_gain	1.0000
6:124283141:GAG:G	donor_gain	1.0000
6:124283143:G:GG	donor_gain	1.0000
6:123804255:G:GG	donor_gain	0.9900
6:123868978:G:GT	donor_gain	0.9900
6:123926359:T:G	donor_gain	0.9900
6:123926359:T:TG	donor_gain	0.9900
6:123945814:G:GG	donor_gain	0.9900
6:123998410:G:A	acceptor_gain	0.9900
6:123998628:G:GT	donor_gain	0.9900
6:124282999:TTCTA:T	acceptor_loss	0.9900
6:124283000:TCTAG:T	acceptor_loss	0.9900
6:124283001:CTAG:C	acceptor_loss	0.9900
6:124283002:TAGGT:T	acceptor_loss	0.9900
6:124283003:A:T	acceptor_loss	0.9900
6:124283004:G:A	acceptor_loss	0.9900
6:124283142:AGT:A	donor_loss	0.9900
6:124283143:G:A	donor_loss	0.9900
6:124283144:TAAGT:T	donor_loss	0.9900
6:124283145:AAGTA:A	donor_loss	0.9900
6:124283146:A:AC	donor_loss	0.9900
6:124283147:G:A	donor_loss	0.9900

AlphaMissense

1356 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:124283050:T:A	W34R	1.000
6:124283050:T:C	W34R	1.000
6:124658234:T:A	W108R	1.000
6:124658234:T:C	W108R	1.000
6:124658255:T:A	C115S	1.000
6:124658256:G:C	C115S	1.000
6:124283033:A:T	D28V	0.999
6:124283041:G:A	G31R	0.999
6:124283041:G:C	G31R	0.999
6:124283042:G:A	G31E	0.999
6:124283052:G:C	W34C	0.999
6:124283052:G:T	W34C	0.999
6:124283098:G:C	G50R	0.999
6:124283099:G:A	G50D	0.999
6:124283107:G:A	G53R	0.999
6:124283107:G:C	G53R	0.999
6:124283108:G:A	G53E	0.999
6:124355276:T:A	W68R	0.999
6:124355276:T:C	W68R	0.999
6:124355288:T:A	W72R	0.999
6:124355288:T:C	W72R	0.999
6:124355297:T:A	W75R	0.999
6:124355297:T:C	W75R	0.999
6:124355302:T:A	N76K	0.999
6:124355302:T:G	N76K	0.999
6:124658229:C:T	S106F	0.999
6:124658231:T:A	W107R	0.999
6:124658231:T:C	W107R	0.999
6:124658233:G:C	W107C	0.999
6:124658233:G:T	W107C	0.999

dbSNP variants (sampled 300 via entrez): RS1000008638 (6:124068382 G>C), RS1000009277 (6:124204082 G>A), RS1000010214 (6:124279277 G>A), RS1000010260 (6:124632101 A>G), RS1000010713 (6:123989013 T>C), RS1000020792 (6:124756933 A>G), RS1000021082 (6:124677179 G>A), RS1000021921 (6:124538851 G>A,C), RS1000022736 (6:124373384 A>G), RS1000031323 (6:123949479 A>G), RS1000031489 (6:124112954 C>G,T), RS1000036665 (6:123939845 G>A), RS1000038727 (6:123989346 T>A), RS1000039213 (6:124028567 A>T), RS1000040147 (6:123997689 C>T)

Disease associations

OMIM: gene MIM:609758 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001521_20	Subcutaneous adipose tissue	1.000000e-06
GCST001851_3	Schizophrenia	4.000000e-06
GCST001915_15	Alzheimer’s disease (cognitive decline)	6.000000e-07
GCST001920_2	QRS duration	3.000000e-06
GCST002127_19	Periodontitis (Mean PAL)	2.000000e-06
GCST002127_31	Periodontitis (Mean PAL)	8.000000e-07
GCST002520_3	Celiac disease	5.000000e-07
GCST002989_12	LDL peak particle diameter (total fat intake interaction)	5.000000e-06
GCST003074_12	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	8.000000e-07
GCST003542_149	Night sleep phenotypes	4.000000e-06
GCST003654_10	Bone mineral density (Ward’s triangle area)	1.000000e-06
GCST004569_1	Neuroticism	3.000000e-07
GCST007470_11	Rapid automatized naming of letters	3.000000e-06
GCST008180_15	Spontaneous preterm birth with premature rupture of membranes	3.000000e-06
GCST009214_3	Third ventricle volume	6.000000e-06
GCST009557_10	Rate of ventricular enlargement	4.000000e-06
GCST010725_71	Malaria	2.000000e-06
GCST010725_88	Malaria	5.000000e-07
GCST010988_376	Adult body size	6.000000e-12
GCST012299_19	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	3.000000e-08
GCST012307_2	Bipolar disorder x sex interaction	1.000000e-06
GCST90000014_4	Parkinson’s disease motor subtype (tremor dominant vs postural instability/gait difficulty)	3.000000e-06
GCST90000047_127	Age at first sexual intercourse	5.000000e-10
GCST90006991_1	Gut microbiota relative abundance (Streptococcus)	9.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007677	LDL peak particle diameter measurement
EFO:0007678	total fat intake measurement
EFO:0007707	cerebral amyloid deposition measurement
EFO:0007785	femoral neck bone mineral density
EFO:0005301	reading and spelling ability
EFO:0006917	spontaneous preterm birth
EFO:0010570	ventricular enlargement measurement
EFO:0008343	sex interaction measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases methylation	4
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	4
Aflatoxin B1	decreases methylation, increases methylation	2
methyleugenol	decreases expression	1
bisphenol A	affects methylation	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Methapyrilene	decreases methylation	1
Tretinoin	increases expression	1
Triclosan	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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