NKAIN3

Summary

NKAIN3 (sodium/potassium transporting ATPase interacting 3, HGNC:26829) is a protein-coding gene on chromosome 8q12.3, encoding Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 3 (Q8N8D7).

NKAIN3 is a member of a family of mammalian proteins (see NKAIN1; MIM 612871) with similarity to Drosophila Nkain (Gorokhova et al., 2007 [PubMed 17606467]).

Source: NCBI Gene 286183 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_001304533

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26829
Approved symbol	NKAIN3
Name	sodium/potassium transporting ATPase interacting 3
Location	8q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ39630
Ensembl gene	ENSG00000185942
Ensembl biotype	protein_coding
OMIM	612872
Entrez	286183

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000519049, ENST00000523211, ENST00000523367, ENST00000524201, ENST00000623646, ENST00000674732, ENST00000674746, ENST00000674864, ENST00000674873, ENST00000675180, ENST00000675749, ENST00000676150

RefSeq mRNA: 2 — MANE Select: NM_001304533 NM_001304533, NM_001410914

CCDS: CCDS94295, CCDS94296

Canonical transcript exons

ENST00000623646 — 7 exons

Exon	Start	End
ENSE00002111545	62953902	62953972
ENSE00002135420	62248854	62249127
ENSE00003538673	62746932	62747129
ENSE00003563497	62589714	62589794
ENSE00003565152	62579539	62579676
ENSE00003654158	62918453	62918513
ENSE00003758519	62965354	62984904

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 95.26.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6845 / max 132.8673, expressed in 362 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89094	0.6890	205
89096	0.4445	141
89092	0.3849	118
89093	0.2915	108
89089	0.2574	94
205205	0.2010	78
89095	0.1460	88
89091	0.1180	71
89097	0.0981	60
89090	0.0541	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.26	gold quality
ganglionic eminence	UBERON:0004023	93.89	gold quality
entorhinal cortex	UBERON:0002728	91.23	gold quality
lateral globus pallidus	UBERON:0002476	87.80	gold quality
sural nerve	UBERON:0015488	85.39	gold quality
postcentral gyrus	UBERON:0002581	85.38	gold quality
temporal lobe	UBERON:0001871	85.24	gold quality
endothelial cell	CL:0000115	83.56	gold quality
superior frontal gyrus	UBERON:0002661	83.51	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.67	gold quality
amygdala	UBERON:0001876	82.66	gold quality
parietal lobe	UBERON:0001872	82.49	gold quality
cortical plate	UBERON:0005343	82.14	gold quality
caudate nucleus	UBERON:0001873	81.78	gold quality
nucleus accumbens	UBERON:0001882	81.19	gold quality
Ammon’s horn	UBERON:0001954	81.06	gold quality
adrenal tissue	UBERON:0018303	81.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.40	gold quality
putamen	UBERON:0001874	80.32	gold quality
dorsal root ganglion	UBERON:0000044	79.99	gold quality
corpus callosum	UBERON:0002336	79.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.07	gold quality
cerebral cortex	UBERON:0000956	77.91	gold quality
substantia nigra pars compacta	UBERON:0001965	76.95	gold quality
anterior cingulate cortex	UBERON:0009835	76.86	gold quality
neocortex	UBERON:0001950	76.37	gold quality
frontal cortex	UBERON:0001870	75.78	gold quality
forebrain	UBERON:0001890	75.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.36	gold quality
middle temporal gyrus	UBERON:0002771	75.00	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-CURD-6	yes	3991.59
E-MTAB-6678	yes	1686.06
E-GEOD-75688	yes	1396.65
E-CURD-97	yes	739.74
E-GEOD-130473	yes	707.40
E-GEOD-114530	yes	624.06
E-MTAB-9154	yes	364.97
E-HCAD-10	yes	281.12
E-GEOD-81547	yes	280.79
E-MTAB-7037	yes	239.89
E-HCAD-35	yes	94.14
E-HCAD-5	yes	37.31
E-HCAD-25	yes	25.94
E-MTAB-5061	yes	16.16
E-CURD-89	no	311.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting NKAIN3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nkain3	ENSMUSG00000055761
rattus_norvegicus	Nkain3	ENSRNOG00000013085
drosophila_melanogaster	NKAIN	FBGN0085442
caenorhabditis_elegans		WBGENE00011760

Paralogs (3): NKAIN1 (ENSG00000084628), NKAIN4 (ENSG00000101198), NKAIN2 (ENSG00000188580)

Protein

Protein identifiers

Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 3 — Q8N8D7 (reviewed: Q8N8D7)

Alternative names: Protein FAM77D

All UniProt accessions (8): A0A6Q8PFE2, A0A6Q8PFI1, A0A6Q8PFP9, A0A6Q8PG07, A0A6Q8PGC9, A0A6Q8PH17, E5RIL3, Q8N8D7

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with ATP1B1.

Subcellular location. Cell membrane.

Similarity. Belongs to the NKAIN family.

RefSeq proteins (2): NP_001291462, NP_001397843 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008516	Na/K-Atpase_Interacting	Family

Pfam: PF05640

UniProt features (6 total): transmembrane region 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8D7-F1	77.17	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): TGACCTY_ERR1_Q2, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_SODIUM_ION_TRANSPORT, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, AACTTT_UNKNOWN, LXR_Q3, HAND1E47_01, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, TGGAAA_NFAT_Q4_01, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, chr8q12, TAL1BETAITF2_01, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN

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

476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKAIN3	TENM4	Q6N022	526
NKAIN3	C3orf22	Q8N5N4	507
NKAIN3	RNASE12	Q5GAN4	476
NKAIN3	FSTL5	Q8N475	454
NKAIN3	SMIM17	P0DL12	447
NKAIN3	C12orf56	Q8IXR9	447
NKAIN3	SH2D7	A6NKC9	431
NKAIN3	C22orf42	Q6IC83	419
NKAIN3	CC2D2B	Q6DHV5	419
NKAIN3	C1orf167	Q5SNV9	419
NKAIN3	ANKRD62	A6NC57	418
NKAIN3	CLPSL1	A2RUU4	414
NKAIN3	MTHFD1	P11586	410
NKAIN3	RAD18	Q9NS91	404
NKAIN3	HS1BP3	Q53T59	402
NKAIN3	EPCIP	Q9NYP8	402

IntAct

0 interactions, top by confidence:

BioGRID (9): NKAIN3 (Positive Genetic), POF1B (Affinity Capture-MS), TRIM29 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), GFAP (Affinity Capture-MS), EVPL (Affinity Capture-MS), PPL (Affinity Capture-MS), EPPK1 (Affinity Capture-MS), NKAIN3 (Affinity Capture-RNA)

ESM2 similar proteins: A2VE13, A4K2N5, A4K2W1, B8BPI2, E1BY51, O09117, O09198, O35682, O62646, O88662, O89104, P21145, Q04941, Q10EJ2, Q16563, Q1RMQ3, Q28296, Q3URJ8, Q3ZBY0, Q5R6H1, Q5RAI2, Q5VXT5, Q64349, Q6DHB5, Q6GPN9, Q6P0C6, Q6P742, Q6VBQ5, Q6Y1E2, Q78S06, Q86TG1, Q86UW1, Q8BI08, Q8CJ61, Q8IZ96, Q8IZR5, Q8N2H4, Q8N8D7, Q91WN2, Q95MN6

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4823 predictions. Top by Δscore:

Variant	Effect	Δscore
8:62249123:AGTTG:A	donor_loss	1.0000
8:62249124:GTTG:G	donor_gain	1.0000
8:62249125:TTGG:T	donor_loss	1.0000
8:62249128:GTG:G	donor_loss	1.0000
8:62277438:A:AG	acceptor_gain	1.0000
8:62277446:T:TA	acceptor_gain	1.0000
8:62332013:G:GT	donor_gain	1.0000
8:62579534:TGTA:T	acceptor_loss	1.0000
8:62579536:TAGGT:T	acceptor_loss	1.0000
8:62579537:A:AT	acceptor_loss	1.0000
8:62747125:TCTCT:T	donor_gain	1.0000
8:62747126:CTCT:C	donor_gain	1.0000
8:62747127:TCT:T	donor_gain	1.0000
8:62747130:G:GG	donor_gain	1.0000
8:62918451:A:AG	acceptor_gain	1.0000
8:62918451:AGTT:A	acceptor_gain	1.0000
8:62918452:G:GG	acceptor_gain	1.0000
8:62918452:GTTG:G	acceptor_gain	1.0000
8:62918514:G:GG	donor_gain	1.0000
8:62249128:G:GG	donor_gain	0.9900
8:62249129:TGAG:T	donor_loss	0.9900
8:62249130:GAGT:G	donor_loss	0.9900
8:62253974:A:AG	acceptor_gain	0.9900
8:62579537:A:AG	acceptor_gain	0.9900
8:62579538:G:GC	acceptor_gain	0.9900
8:62579672:TGGTG:T	donor_gain	0.9900
8:62579673:GGTGG:G	donor_gain	0.9900
8:62579674:GTG:G	donor_gain	0.9900
8:62579674:GTGGT:G	donor_loss	0.9900
8:62579675:TGGTA:T	donor_loss	0.9900

AlphaMissense

1425 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:62579584:T:A	W34R	0.998
8:62579584:T:C	W34R	0.998
8:62589744:T:A	W75R	0.998
8:62589744:T:C	W75R	0.998
8:62589749:T:A	N76K	0.998
8:62589749:T:G	N76K	0.998
8:62746979:G:C	W107C	0.998
8:62746979:G:T	W107C	0.998
8:62579556:G:C	R24S	0.997
8:62579556:G:T	R24S	0.997
8:62579586:G:C	W34C	0.997
8:62579586:G:T	W34C	0.997
8:62579604:T:A	N40K	0.997
8:62579604:T:G	N40K	0.997
8:62579642:G:A	G53E	0.997
8:62589723:T:A	W68R	0.997
8:62589723:T:C	W68R	0.997
8:62746976:G:C	W106C	0.997
8:62746976:G:T	W106C	0.997
8:62746977:T:A	W107R	0.997
8:62746977:T:C	W107R	0.997
8:62747106:A:C	S150R	0.997
8:62747108:T:A	S150R	0.997
8:62747108:T:G	S150R	0.997
8:62579567:A:T	D28V	0.996
8:62589735:T:A	W72R	0.996
8:62589735:T:C	W72R	0.996
8:62746998:T:A	C114S	0.996
8:62746999:G:C	C114S	0.996
8:62579555:G:C	R24T	0.995

dbSNP variants (sampled 300 via entrez): RS1000000038 (8:62587167 C>T), RS1000006434 (8:62898629 A>G), RS1000009755 (8:62637685 A>G), RS1000016979 (8:62460861 C>G,T), RS1000017862 (8:62521014 A>T), RS1000019643 (8:62668866 G>A,C,T), RS1000021137 (8:62426877 G>A), RS1000025923 (8:62699102 G>A,T), RS1000027440 (8:62783855 G>A), RS1000028435 (8:62366341 C>T), RS1000031100 (8:62452473 C>T), RS1000031843 (8:62845031 A>G), RS1000033613 (8:62539254 A>G), RS1000042693 (8:62801682 A>G), RS1000046122 (8:62894219 G>A)

Disease associations

OMIM: gene MIM:612872 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001450_1	Response to Vitamin E supplementation	6.000000e-07
GCST001958_20	Bulimia nervosa	9.000000e-07
GCST002136_6	Periodontitis (PAL4Q3)	7.000000e-06
GCST002337_44	Amyotrophic lateral sclerosis (sporadic)	2.000000e-06
GCST002550_9	Allergic rhinitis	3.000000e-07
GCST002829_15	Urate levels in overweight individuals	4.000000e-06
GCST005240_2	Caudate volume in trauma-exposed individuals	8.000000e-07
GCST007470_12	Rapid automatized naming of letters	2.000000e-08
GCST008163_289	Height	2.000000e-06
GCST009698_49	Metabolite levels	2.000000e-08
GCST010396_248	Gut microbiota (bacterial taxa, hurdle binary method)	5.000000e-06
GCST011823_1	Parkinson’s disease progression (cognitive)	6.000000e-08
GCST012490_33	Femur bone mineral density x serum urate levels interaction	3.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004830	caudate nucleus volume
EFO:0008483	response to trauma exposure
EFO:0005301	reading and spelling ability
EFO:0009771	methionine measurement
EFO:0007874	gut microbiome measurement
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10504361	NKAIN3		0.00	0

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	8
methylmercuric chloride	decreases expression, affects cotreatment	4
trichostatin A	affects cotreatment, decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
theaflavin-3,3’-digallate	affects expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Drugs, Chinese Herbal	decreases expression	1
Chlordecone	affects response to substance	1
Nickel	decreases expression	1
Pesticides	increases methylation	1
Triclosan	increases expression	1
Okadaic Acid	decreases expression	1
Permethrin	increases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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