KCNAB2

Summary

KCNAB2 (potassium voltage-gated channel subfamily A regulatory beta subunit 2, HGNC:6229) is a protein-coding gene on chromosome 1p36.31, encoding Voltage-gated potassium channel subunit beta-2 (Q13303). Regulatory subunit of the voltage-gated potassium (Kv) Shaker channels composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits.

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member is one of the beta subunits, which are auxiliary proteins associating with functional Kv-alpha subunits. This member alters functional properties of the KCNA4 gene product. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 8514 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 110 total
• Phenotypes (HPO): 99
• Druggable target: yes
• MANE Select transcript: NM_001199862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6229
Approved symbol	KCNAB2
Name	potassium voltage-gated channel subfamily A regulatory beta subunit 2
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Aliases	AKR6A5, KCNA2B, HKvbeta2.1, HKvbeta2.2
Ensembl gene	ENSG00000069424
Ensembl biotype	protein_coding
OMIM	601142
Entrez	8514

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 29 protein_coding, 9 retained_intron, 6 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000164247, ENST00000341524, ENST00000352527, ENST00000378083, ENST00000378092, ENST00000378097, ENST00000378111, ENST00000389632, ENST00000428161, ENST00000435937, ENST00000445501, ENST00000458166, ENST00000459822, ENST00000462676, ENST00000472700, ENST00000478098, ENST00000481789, ENST00000493807, ENST00000602612, ENST00000652845, ENST00000652911, ENST00000653262, ENST00000653635, ENST00000654144, ENST00000655548, ENST00000655703, ENST00000655748, ENST00000656198, ENST00000656607, ENST00000656746, ENST00000657222, ENST00000658691, ENST00000658883, ENST00000661248, ENST00000662147, ENST00000662363, ENST00000662815, ENST00000663169, ENST00000663419, ENST00000663671, ENST00000665338, ENST00000666163, ENST00000666299, ENST00000668559, ENST00000668706, ENST00000669250, ENST00000671076, ENST00000671676

RefSeq mRNA: 6 — MANE Select: NM_001199862 NM_001199860, NM_001199861, NM_001199862, NM_001199863, NM_003636, NM_172130

CCDS: CCDS55, CCDS55570, CCDS55571, CCDS56

Canonical transcript exons

ENST00000378083 — 16 exons

Exon	Start	End
ENSE00000734868	6096636	6096756
ENSE00000734870	6095530	6095624
ENSE00000734876	6094400	6094485
ENSE00000734879	6090389	6090475
ENSE00000734882	6089008	6089051
ENSE00000734884	6087467	6087511
ENSE00001476195	6091263	6091307
ENSE00001476199	6051511	6051754
ENSE00001615557	6095323	6095443
ENSE00002290012	6045888	6046183
ENSE00002941030	6085204	6085248
ENSE00003484943	6097269	6097357
ENSE00003493562	6073733	6073770
ENSE00003680188	6072755	6072798
ENSE00003759247	6082195	6082274
ENSE00003875419	6098485	6101180

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 98.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.1030 / max 1074.2946, expressed in 1757 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
352	16.2480	635
347	12.5176	1708
353	7.8301	529
351	1.2626	361
350	1.0457	370
346	0.0626	25
354	0.0468	25
356	0.0402	14
355	0.0265	15
357	0.0229	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	98.40	gold quality
right frontal lobe	UBERON:0002810	98.35	gold quality
pons	UBERON:0000988	98.11	gold quality
cingulate cortex	UBERON:0003027	97.95	gold quality
anterior cingulate cortex	UBERON:0009835	97.93	gold quality
granulocyte	CL:0000094	97.91	gold quality
prefrontal cortex	UBERON:0000451	97.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.48	gold quality
frontal cortex	UBERON:0001870	97.14	gold quality
frontal lobe	UBERON:0016525	97.14	gold quality
nucleus accumbens	UBERON:0001882	97.04	gold quality
amygdala	UBERON:0001876	97.00	gold quality
dorsal root ganglion	UBERON:0000044	96.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.62	gold quality
neocortex	UBERON:0001950	96.49	gold quality
frontal pole	UBERON:0002795	96.46	gold quality
parietal lobe	UBERON:0001872	96.32	gold quality
putamen	UBERON:0001874	96.18	gold quality
postcentral gyrus	UBERON:0002581	95.96	gold quality
monocyte	CL:0000576	95.82	gold quality
temporal lobe	UBERON:0001871	95.77	gold quality
Ammon’s horn	UBERON:0001954	95.75	gold quality
cerebral cortex	UBERON:0000956	95.74	gold quality
telencephalon	UBERON:0001893	95.65	gold quality
leukocyte	CL:0000738	95.61	gold quality
mononuclear cell	CL:0000842	95.48	gold quality
caudate nucleus	UBERON:0001873	95.38	gold quality
superior frontal gyrus	UBERON:0002661	95.29	gold quality
CA1 field of hippocampus	UBERON:0003881	94.73	gold quality
forebrain	UBERON:0001890	94.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	13.01
E-ANND-3	yes	9.67
E-MTAB-5061	no	3.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, NEUROD1

miRNA regulators (miRDB)

137 targeting KCNAB2, 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-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4306	99.72	70.50	3630

Literature-anchored findings (GeneRIF, showing 5)

• Results identified gain and loss of function mutations which lead to increased and decreased potassium currents enhancing AF. (PMID:23264583)
• Incretin regulation of beta-cell function involves the acetylation of Kv beta2. (PMID:23390957)
• The results show that KvBeta 2 dysregulation of Kv4.3 is involved in the pathogenesis of Brugada Syndrome. This new finding also expands the list of genes associated with susceptibility to BrS and may contribute to improve molecular diagnosis of this cardiac arrhythmia disorder. (PMID:27287695)
• Role of KCNAB2 expression in modulating hormone secretion in somatotroph pituitary adenoma. (PMID:32109873)
• The Ion Channel Gene KCNAB2 Is Associated with Poor Prognosis and Loss of Immune Infiltration in Lung Adenocarcinoma. (PMID:36359834)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnab2b	ENSDARG00000062134
danio_rerio	kcnab2a	ENSDARG00000087247
mus_musculus	Kcnab2	ENSMUSG00000028931
rattus_norvegicus	Kcnab2	ENSRNOG00000011550
drosophila_melanogaster	CG18547	FBGN0037973
drosophila_melanogaster	CG3397	FBGN0037975
caenorhabditis_elegans		WBGENE00003176
caenorhabditis_elegans		WBGENE00009980
caenorhabditis_elegans		WBGENE00009981
caenorhabditis_elegans		WBGENE00012722
caenorhabditis_elegans		WBGENE00012723
caenorhabditis_elegans		WBGENE00015307

Paralogs (16): AKR7A2 (ENSG00000053371), AKR1B1 (ENSG00000085662), AKR1A1 (ENSG00000117448), AKR1D1 (ENSG00000122787), AKR1C2 (ENSG00000151632), AKR7A3 (ENSG00000162482), AKR1E2 (ENSG00000165568), KCNAB1 (ENSG00000169282), KCNAB3 (ENSG00000170049), AKR1C1 (ENSG00000187134), AKR1C3 (ENSG00000196139), AKR1B10 (ENSG00000198074), AKR1C4 (ENSG00000198610), AKR7L (ENSG00000211454), AKR1B15 (ENSG00000227471), AKR1C8 (ENSG00000264006)

Protein

Protein identifiers

Voltage-gated potassium channel subunit beta-2 — Q13303 (reviewed: Q13303)

Alternative names: K(+) channel subunit beta-2, Kv-beta-2

All UniProt accessions (22): Q13303, A0A590UJ15, A0A590UJ35, A0A590UJ72, A0A590UJ79, A0A590UJB6, A0A590UJB8, A0A590UJI8, A0A590UJJ4, A0A590UJK5, A0A590UJU1, A0A590UJU4, A0A590UJV4, A0A590UJX9, A0A590UJY1, A0A590UK89, A0A5F9UN28, K7EIR5, K7EKU4, Q5TG78, Q5TG81, Q5TG84

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the voltage-gated potassium (Kv) Shaker channels composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits. The beta-2/KCNAB2 cytoplasmic subunit promotes potassium channel closure via a mechanism that does not involve physical obstruction of the channel pore. Promotes the inactivation of Kv1.4/KCNA4 and Kv1.5/KCNA5 alpha subunit-containing channels. Displays nicotinamide adenine dinucleotide phosphate (NADPH)-dependent aldoketoreductase activity by catalyzing the NADPH-dependent reduction of a wide range of aldehyde and ketone substrates. Substrate specificity includes methylglyoxal, 9,10-phenanthrenequinone, prostaglandin J2, 4-nitrobenzaldehyde, 4-nitroacetophenone and 4-oxo-trans-2-nonenal (in vitro, no physiological substrate identified yet). The binding of oxidized and reduced nucleotide alters Kv channel gating and may contribute to dynamic fine tuning of cell excitability. Contributes to the regulation of nerve signaling, and prevents neuronal hyperexcitability.

Subunit / interactions. Homotetramer. Interaction with tetrameric potassium channel alpha subunits gives rise to a heterooctamer. Identified in potassium channel complexes containing KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNAB1, KCNAB2 and KCND3. Interacts (in unphosphorylated form) with MAPRE1. Forms a ternary complex with SQSTM1 and PRKCZ.

Subcellular location. Cytoplasm. Membrane. Cell membrane. Cell projection. Axon. Synapse. Synaptosome. Cytoskeleton.

Tissue specificity. Detected in myelinated nerve fibers in the spinal cord, in the juxtaparanodal region of the nodes of Ranvier, but also in the paranodal region. Detected in hippocampus (at protein level). Detected in hippocampus.

Post-translational modifications. Phosphorylated by PRKCZ; may be regulated by incorporation in a complex composed of PRKCZ and SQSTM1.

Domain organisation. In contrast to KCNAB1, the shorter N-terminal domain of KCNAB2 cannot mediate closure of delayed rectifier potassium channels by physically obstructing the pore.

Similarity. Belongs to the shaker potassium channel beta subunit family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q13303-1	1, KvB2.1	yes
Q13303-2	2, KvB2.2
Q13303-3	3
Q13303-4	4
Q13303-5	5

RefSeq proteins (6): NP_001186789, NP_001186790, NP_001186791, NP_001186792, NP_003627, NP_742128 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005399	K_chnl_volt-dep_bsu_KCNAB-rel	Family
IPR005401	K_chnl_volt-dep_bsu_KCNAB2	Family
IPR005983	K_chnl_volt-dep_bsu_KCNAB	Family
IPR023210	NADP_OxRdtase_dom	Domain
IPR036812	NAD(P)_OxRdtase_dom_sf	Homologous_superfamily

Pfam: PF00248

Catalyzed reactions (Rhea), 2 shown:

• hydroxyacetone + NADP(+) = methylglyoxal + NADPH + H(+) (RHEA:27986)
• (E)-4-oxonon-2-en-1-ol + NADP(+) = (E)-4-oxonon-2-enal + NADPH + H(+) (RHEA:58432)

UniProt features (74 total): binding site 22, helix 20, strand 15, modified residue 8, splice variant 5, chain 1, active site 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1ZSX	X-RAY DIFFRACTION	1.9
7EJ1	ELECTRON MICROSCOPY	3.2
7EJ2	ELECTRON MICROSCOPY	3.3
7WF3	ELECTRON MICROSCOPY	3.4
7WF4	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13303-F1	91.25	0.87

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): 90 (proton donor/acceptor)

Ligand- & substrate-binding residues (22): 243; 244; 245; 246; 247; 248; 254; 262; 264; 323; 56; 325 …

Post-translational modifications (8): 9, 14, 20, 28, 28, 31, 112, 124

Mutagenesis-validated functional residues (1):

Position	Phenotype
90	no effect on its activity in promoting kcna4 channel closure.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-6798695	Neutrophil degranulation
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 487 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, GOCC_SECRETORY_GRANULE, REACTOME_POTASSIUM_CHANNELS, MODULE_45, WHITE_NEUROBLASTOMA_WITH_1P36.3_DELETION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, RAMALHO_STEMNESS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, RYTTCCTG_ETS2_B, GOBP_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, P300_01, NRF2_01

GO Biological Process (6): regulation of potassium ion transmembrane transport (GO:1901379), regulation of protein localization to cell surface (GO:2000008), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), transmembrane transport (GO:0055085), potassium ion transmembrane transport (GO:0071805)

GO Molecular Function (7): voltage-gated potassium channel activity (GO:0005249), alcohol dehydrogenase (NADP+) activity (GO:0008106), potassium channel regulator activity (GO:0015459), transmembrane transporter binding (GO:0044325), methylglyoxal reductase (NADPH) (acetol producing) activity (GO:1990002), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (16): cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), cytoplasmic side of plasma membrane (GO:0009898), membrane (GO:0016020), specific granule membrane (GO:0035579), juxtaparanode region of axon (GO:0044224), synapse (GO:0045202), tertiary granule membrane (GO:0070821), pinceau fiber (GO:1990031), cytoplasm (GO:0005737), microtubule (GO:0005874), axon (GO:0030424), cell projection (GO:0042995), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Potassium Channels	1
Innate Immune System	1
Neuronal System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
transport	2
potassium channel activity	2
secretory granule membrane	2
regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of monoatomic cation transmembrane transport	1
regulation of protein localization	1
protein localization to cell surface	1
metal ion transport	1
cellular process	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
voltage-gated monoatomic cation channel activity	1
alcohol dehydrogenase [NAD(P)+] activity	1
ion channel regulator activity	1
protein binding	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
plasma membrane	1
cytoplasmic side of membrane	1
specific granule	1
main axon	1
cell junction	1
tertiary granule	1
axon	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
neuron projection	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2061 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNAB2	KCNA2	P16389	994
KCNAB2	KCNA1	Q09470	985
KCNAB2	KCNA4	P22459	962
KCNAB2	KCNA5	P22460	857
KCNAB2	KCNA6	P17658	785
KCNAB2	CNTNAP2	Q9UHC6	783
KCNAB2	DLG1	Q12959	780
KCNAB2	PRKCZ	Q05513	769
KCNAB2	KCND2	Q9NZV8	744
KCNAB2	KCNC1	P48547	742
KCNAB2	SLC39A1	Q9NY26	712
KCNAB2	KIF3A	Q9Y496	681
KCNAB2	CNTNAP1	P78357	665
KCNAB2	SQSTM1	Q13501	665
KCNAB2	KCNC4	Q03721	641

IntAct

46 interactions, top by confidence:

A	B	Type	Score
ANKRD44	PPP6C	psi-mi:“MI:0914”(association)	0.790
KCNA2	KCNAB2	psi-mi:“MI:0915”(physical association)	0.670
APP	KCNAB2	psi-mi:“MI:0915”(physical association)	0.560
HTT	KCNAB2	psi-mi:“MI:0915”(physical association)	0.560
KCNAB1	KCNAB2	psi-mi:“MI:0915”(physical association)	0.560
CCAR2	HSPA8	psi-mi:“MI:0914”(association)	0.550
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
KCNA10	GAPDHS	psi-mi:“MI:0914”(association)	0.530
KCNA6	KCNA3	psi-mi:“MI:0914”(association)	0.530
KCNA2	KCNA3	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530
KCNAB3	KCNAB2	psi-mi:“MI:0914”(association)	0.500
KCNAB3	KCNAB2	psi-mi:“MI:0915”(physical association)	0.500
	KCNAB2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNAB2	TNNC2	psi-mi:“MI:0915”(physical association)	0.400
HAO1	KCNAB2	psi-mi:“MI:0915”(physical association)	0.400
KCNAB2	KCNAB2	psi-mi:“MI:0915”(physical association)	0.370
SPG11	KCNAB2	psi-mi:“MI:0915”(physical association)	0.370
MAPT	SEPTIN8	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
KCNA4	POLRMT	psi-mi:“MI:0914”(association)	0.350
	EIF3F	psi-mi:“MI:0914”(association)	0.350
	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
	DDX3X	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350

BioGRID (74): KCNAB2 (Two-hybrid), KCNAB2 (Affinity Capture-MS), KCNAB1 (Affinity Capture-MS), GAPVD1 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS), ATIC (Co-fractionation), KCNAB2 (Co-fractionation), KCNAB2 (Co-fractionation), NUTF2 (Co-fractionation), KCNAB2 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EV45, C9WPN6, F1QGW6, F6RQL9, O73723, O77676, P00516, P0C605, P20461, P23258, P23330, P31321, P32392, P35250, P41091, P53033, P61157, P61158, P62482, P62483, P81795, P83887, P83888, Q05B83, Q0VCD2, Q13126, Q13303, Q13976, Q27955, Q2KHU8, Q2KJ81, Q2VIR3, Q32KM1, Q4V7C7, Q5R797, Q5R8R1, Q5ZHS1, Q5ZMS3, Q641P0, Q641W4

Diamond homologs: B9WYE6, C6TBN2, C7ZBE5, E9FCP6, F4HPY8, G2TRN6, M2YJQ2, M2YMU7, O05408, O22707, O23016, O59826, P40691, P49249, P62482, P62483, P77735, Q02895, Q13303, Q27955, Q3L181, Q40648, Q63494, Q75ZG2, Q75ZG3, Q84M96, Q93ZN2, Q9ASZ9, Q9P7U2, Q9PTM4, Q9PTM5, Q9PWR1, A0A0U5GHU6, C8VQ93, O43448, P40690, P43547, P54569, P63143, P63144

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Voltage gated Potassium channels	8	54.0×	3e-10
Potassium Channels	9	33.6×	4e-10
Neuronal System	10	12.3×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
action potential	6	47.8×	4e-07
potassium ion transport	9	38.3×	7e-10
potassium ion transmembrane transport	8	24.2×	3e-07
protein homooligomerization	7	19.0×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	34
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

4692 predictions. Top by Δscore:

Variant	Effect	Δscore
1:6073767:TGAGG:T	donor_loss	1.0000
1:6073769:AGGTA:A	donor_loss	1.0000
1:6073770:GGTA:G	donor_loss	1.0000
1:6073772:T:A	donor_loss	1.0000
1:6082271:GCAA:G	donor_gain	1.0000
1:6082275:G:GG	donor_gain	1.0000
1:6087509:A:T	donor_gain	1.0000
1:6087512:G:GG	donor_gain	1.0000
1:6090385:CCA:C	acceptor_loss	1.0000
1:6090386:CA:C	acceptor_loss	1.0000
1:6090387:A:AG	acceptor_gain	1.0000
1:6090387:A:T	acceptor_loss	1.0000
1:6090388:G:A	acceptor_loss	1.0000
1:6090388:G:GG	acceptor_gain	1.0000
1:6090471:GGAAG:G	donor_gain	1.0000
1:6090472:GAAGG:G	donor_gain	1.0000
1:6090474:AGG:A	donor_loss	1.0000
1:6090476:G:GG	donor_gain	1.0000
1:6090477:T:G	donor_loss	1.0000
1:6095321:A:AG	acceptor_gain	1.0000
1:6095322:G:GA	acceptor_gain	1.0000
1:6095322:GGA:G	acceptor_gain	1.0000
1:6095410:G:GT	donor_gain	1.0000
1:6095439:GA:G	donor_gain	1.0000
1:6095440:ATAG:A	donor_loss	1.0000
1:6095524:CTTCA:C	acceptor_loss	1.0000
1:6095525:TTCAG:T	acceptor_loss	1.0000
1:6095526:TCA:T	acceptor_loss	1.0000
1:6095527:CAGGA:C	acceptor_loss	1.0000
1:6095528:A:AG	acceptor_gain	1.0000

AlphaMissense

2708 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6073738:T:A	W57R	0.999
1:6073738:T:C	W57R	0.999
1:6082220:C:A	A76D	0.999
1:6082241:T:C	L83P	0.999
1:6094406:T:A	V170D	0.999
1:6094450:T:A	W185R	0.999
1:6094450:T:C	W185R	0.999
1:6094465:T:A	W190R	0.999
1:6094465:T:C	W190R	0.999
1:6095339:C:A	A202D	0.999
1:6095547:T:A	W243R	0.999
1:6095547:T:C	W243R	0.999
1:6097271:T:A	W310R	0.999
1:6097271:T:C	W310R	0.999
1:6072781:T:A	V49D	0.998
1:6072792:G:A	G53R	0.998
1:6072792:G:C	G53R	0.998
1:6072793:G:A	G53E	0.998
1:6072798:G:A	G55R	0.998
1:6072798:G:C	G55R	0.998
1:6073733:G:A	G55E	0.998
1:6082244:T:C	F84S	0.998
1:6082246:G:C	D85H	0.998
1:6082246:G:T	D85Y	0.998
1:6082247:A:C	D85A	0.998
1:6082247:A:T	D85V	0.998
1:6085244:T:A	W108R	0.998
1:6085244:T:C	W108R	0.998
1:6087481:T:A	V114D	0.998
1:6087494:G:C	K118N	0.998

dbSNP variants (sampled 300 via entrez): RS1000023758 (1:6021465 T>C), RS1000027265 (1:6057876 C>G), RS1000034168 (1:6099821 G>A), RS1000053281 (1:6021757 A>G), RS1000096926 (1:6095825 A>C,G), RS1000106190 (1:6089338 G>A), RS1000120515 (1:6062774 A>G), RS1000185681 (1:6027653 G>A), RS1000190971 (1:6061540 C>T), RS1000201250 (1:6016950 C>T), RS1000209261 (1:6065566 C>G), RS1000216064 (1:6062600 A>G), RS1000217057 (1:6096028 C>G), RS1000256410 (1:5992264 G>A,C), RS1000303911 (1:6062545 A>C)

Disease associations

OMIM: gene MIM:601142 | disease phenotypes: MIM:256100

GenCC curated gene-disease

Mondo (1): nephronophthisis (MONDO:0019005)

Orphanet (1): Nephronophthisis (Orphanet:655)

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000055	Abnormal female external genitalia morphology
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000160	Narrow mouth
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000464	Abnormality of the neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000717	Autism

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1991	Metabolite levels	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005058	tyrosine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066520 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, increases expression, affects cotreatment	4
sodium arsenite	decreases methylation, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
tamibarotene	affects expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	affects response to substance	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Carmustine	affects response to substance	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Etoposide	affects response to substance	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Mitoxantrone	affects response to substance	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5638875	Binding	Inhibition of recombinant human KCNK2 transfected in HEK293 cells assessed as reduction in thallium influx at 30 uM incubated for 15 mins in dark by FLIPR assay relative to control	Discovery of CVN293, a Brain Permeable KCNK13 (THIK-1) Inhibitor Suitable for Clinical Assessment. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YA59	IDG-HEK293T-KCNAB2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01022957	Not specified	COMPLETED	Nephronophthisis : Clinical and Genetic Study
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05286632	Not specified	COMPLETED	KidneYou - Innovative Digital Therapy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies