KCNRG

Summary

KCNRG (potassium channel regulator, HGNC:18893) is a protein-coding gene on chromosome 13q14.2, encoding Potassium channel regulatory protein (Q8N5I3). Inhibits potassium fluxes in cells.

This gene encodes a protein which regulates the activity of voltage-gated potassium channels. This gene is on chromosome 13 and overlaps the gene for tripartite motif containing 13 on the same strand. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 283518 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_173605

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18893
Approved symbol	KCNRG
Name	potassium channel regulator
Location	13q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198553
Ensembl biotype	protein_coding
OMIM	607947
Entrez	283518

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000312942, ENST00000360473

RefSeq mRNA: 2 — MANE Select: NM_173605 NM_173605, NM_199464

CCDS: CCDS41889, CCDS9424

Canonical transcript exons

ENST00000312942 — 2 exons

Exon	Start	End
ENSE00001642676	50020214	50020922
ENSE00003844571	50015444	50016071

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 96.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0390 / max 15.1266, expressed in 12 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135137	0.0303	10
135136	0.0086	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.67	gold quality
fallopian tube	UBERON:0003889	80.07	gold quality
colonic epithelium	UBERON:0000397	69.79	gold quality
endometrium	UBERON:0001295	67.96	gold quality
stromal cell of endometrium	CL:0002255	67.35	gold quality
sural nerve	UBERON:0015488	67.04	gold quality
right lung	UBERON:0002167	66.81	gold quality
adrenal tissue	UBERON:0018303	65.45	gold quality
corpus callosum	UBERON:0002336	65.36	gold quality
ventricular zone	UBERON:0003053	65.05	gold quality
calcaneal tendon	UBERON:0003701	64.88	gold quality
skeletal muscle tissue	UBERON:0001134	64.82	gold quality
lung	UBERON:0002048	64.32	gold quality
bone element	UBERON:0001474	63.83	gold quality
bone marrow	UBERON:0002371	63.83	gold quality
muscle tissue	UBERON:0002385	62.86	gold quality
left uterine tube	UBERON:0001303	62.65	gold quality
monocyte	CL:0000576	62.26	gold quality
leukocyte	CL:0000738	62.13	gold quality
blood	UBERON:0000178	61.44	gold quality
bone marrow cell	CL:0002092	61.32	silver quality
embryo	UBERON:0000922	61.25	gold quality
ganglionic eminence	UBERON:0004023	61.25	gold quality
upper lobe of left lung	UBERON:0008952	61.13	gold quality
tonsil	UBERON:0002372	60.03	gold quality
endocervix	UBERON:0000458	59.62	gold quality
esophagus mucosa	UBERON:0002469	59.59	gold quality
skin of leg	UBERON:0001511	59.38	gold quality
esophagus	UBERON:0001043	59.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting KCNRG, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-7843-3P	98.31	67.94	803
HSA-MIR-6831-5P	98.26	67.20	990

Literature-anchored findings (GeneRIF, showing 6)

• KCNRG suppresses K+ channel activity in human prostate cell line LNCaP. (PMID:12650944)
• the primary characterization of a new gene KCNRG mapped at chromosome band 13q14.3; is a candidate for a B-cell chronic lymphocytic leukemia and prostate cancer tumor suppressor gene (PMID:12650944)
• Results suggest that genetic alterations and the expression of KCNRG might play an important role in the development and/or progression of a subset of hepatocellular carcinoma. (PMID:16819283)
• Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms in autoimmune polyendocrine syndrome type 1 (PMID:19251657)
• KCNRG is an ER-associated protein, which is proposed to regulate Kv1 family channel proteins by retaining a fraction of channels in endomembranes. (PMID:19968958)
• The haploinsufficiency of KCNRG might be relevant to the progression of chronic lymphocytic leukemia (CLL)and multiple myeloma(MM) at least in a subset of patients. (PMID:20237900)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kcnrg	ENSMUSG00000046168
drosophila_melanogaster	twz	FBGN0034636
caenorhabditis_elegans	F32B4.5	WBGENE00009315

Paralogs (13): KCTD1 (ENSG00000134504), KCTD14 (ENSG00000151364), KCTD15 (ENSG00000153885), KCTD18 (ENSG00000155729), KCTD6 (ENSG00000168301), KCTD19 (ENSG00000168676), KCTD12 (ENSG00000178695), KCTD4 (ENSG00000180332), KCTD16 (ENSG00000183775), KCTD8 (ENSG00000183783), KCTD21 (ENSG00000188997), KCTD11 (ENSG00000213859), KCTD7 (ENSG00000243335)

Protein

Protein identifiers

Potassium channel regulatory protein — Q8N5I3 (reviewed: Q8N5I3)

Alternative names: Protein CLLD4

All UniProt accessions (1): Q8N5I3

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits potassium fluxes in cells. May regulate Kv1 family channel proteins by retaining a fraction of channels in endomembranes.

Subunit / interactions. Can form homooligomers. Interacts with KCNA1 (via cytoplasmic N-terminal domain) and KCNA4.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Ubiquitous in normal tissues and expressed in some tumor tissues.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N5I3-1	1, B	yes
Q8N5I3-2	2, A

RefSeq proteins (2): NP_775876, NP_955751 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily

Pfam: PF02214

UniProt features (4 total): splice variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5I3-F1	81.46	0.54

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, EFC_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_POTASSIUM_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_REGULATION_OF_DELAYED_RECTIFIER_POTASSIUM_CHANNEL_ACTIVITY, GOBP_PROTEIN_HOMOOLIGOMERIZATION, ACTTTAT_MIR1425P, GOBP_REGULATION_OF_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_POTASSIUM_ION_TRANSMEMBRANE_TRANSPORT

GO Biological Process (2): protein homooligomerization (GO:0051260), negative regulation of delayed rectifier potassium channel activity (GO:1902260)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein complex oligomerization	1
delayed rectifier potassium channel activity	1
regulation of delayed rectifier potassium channel activity	1
negative regulation of voltage-gated potassium channel activity	1
protein binding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1252 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNRG	TRIM13	O60858	932
KCNRG	SPRYD7	Q5W111	675
KCNRG	BPIFB1	Q8TDL5	670
KCNRG	BTBD10	Q9BSF8	579
KCNRG	TRIM17	Q9Y577	573
KCNRG	TRAT1	Q6PIZ9	547
KCNRG	TNFAIP1	Q13829	541
KCNRG	TGM4	P49221	514
KCNRG	TRIM27	P14373	493
KCNRG	DLEU7	Q6UYE1	485
KCNRG	AIRE	O43918	482
KCNRG	KCTD20	Q7Z5Y7	468
KCNRG	BBOX1	O75936	466
KCNRG	KCTD19	Q17RG1	466
KCNRG	PDILT	Q8N807	451
KCNRG	NLRP5	P59047	451

IntAct

21 interactions, top by confidence:

A	B	Type	Score
KCNRG	KCNRG	psi-mi:“MI:0915”(physical association)	0.820
RFPL4A	KCNRG	psi-mi:“MI:0915”(physical association)	0.560
KCNRG	FOSL1	psi-mi:“MI:0915”(physical association)	0.400
PB2	KCNRG	psi-mi:“MI:0915”(physical association)	0.370
KCNRG	ARHGDIA	psi-mi:“MI:0915”(physical association)	0.370
KCNRG	ROBO2	psi-mi:“MI:0915”(physical association)	0.370
CCNK	KCNRG	psi-mi:“MI:0915”(physical association)	0.370
DGCR6L	KCNRG	psi-mi:“MI:0915”(physical association)	0.370
FXR2	KCNRG	psi-mi:“MI:0915”(physical association)	0.370
KCNRG	KCNRG	psi-mi:“MI:0915”(physical association)	0.000
	KCNRG	psi-mi:“MI:0915”(physical association)	0.000
KCNRG	metE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): KCNRG (Two-hybrid), KCNRG (Two-hybrid), KCNRG (Two-hybrid), KCNRG (Two-hybrid), KCNRG (Two-hybrid), KCNRG (Two-hybrid), KCNRG (Affinity Capture-Western), KCNRG (Two-hybrid), RFPL4A (Two-hybrid), FOSL1 (Affinity Capture-MS), KCNRG (Protein-RNA), KCNRG (Affinity Capture-Western), KCTD5 (FRET), KCNRG (Affinity Capture-Western), KCNRG (Affinity Capture-Western)

ESM2 similar proteins: A0A0K3AV08, A5PF44, A8WW61, B6VQ60, D5SHR0, G5EDM7, G5EFQ5, O13839, O44757, O94532, O94662, O96838, P21293, P32742, P33802, Q03607, Q09291, Q09354, Q09663, Q18262, Q1LVQ2, Q21209, Q21341, Q23238, Q2KHT3, Q2QUS0, Q2TUM3, Q3LRZ3, Q3URF8, Q4G0X4, Q4UKJ5, Q5U243, Q66HD5, Q6DK85, Q6GPD0, Q863D4, Q86ME2, Q8AXQ3, Q8BFX3, Q8CI96

Diamond homologs: A3KMV1, A4IFB4, A5PKG7, A6H6X4, B1WC97, B5DEL1, D5SHR0, G5EFC3, O65555, P0C5J9, P15388, P17971, P17972, P25122, P48547, P59994, P59995, Q01956, Q03607, Q03719, Q0VD00, Q0VFV7, Q14003, Q14681, Q29RJ0, Q2HJ48, Q2TUM3, Q3URF8, Q4G0X4, Q50H33, Q52PG9, Q54KH0, Q5DTY9, Q5M956, Q5XJ34, Q5ZJP7, Q62897, Q63881, Q63959, Q68DU8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

440 predictions. Top by Δscore:

Variant	Effect	Δscore
13:50020208:TCCTA:T	acceptor_loss	1.0000
13:50020209:CCTAG:C	acceptor_loss	1.0000
13:50020210:CTAGG:C	acceptor_loss	1.0000
13:50020211:TA:T	acceptor_loss	1.0000
13:50020212:A:G	acceptor_loss	1.0000
13:50020213:G:A	acceptor_loss	1.0000
13:50020213:GGTAT:G	acceptor_gain	1.0000
13:50015361:GAATC:G	donor_gain	0.9900
13:50020213:GGT:G	acceptor_gain	0.9900
13:50015365:C:CG	donor_gain	0.9800
13:50020212:A:AG	acceptor_gain	0.9800
13:50020213:G:GG	acceptor_gain	0.9800
13:50020213:GGTA:G	acceptor_gain	0.9800
13:50015350:T:TA	donor_gain	0.9700
13:50015351:A:AA	donor_gain	0.9700
13:50015365:C:G	donor_gain	0.9700
13:50018359:A:G	acceptor_gain	0.9600
13:50018795:G:GC	acceptor_gain	0.9600
13:50018821:AGGCT:A	acceptor_gain	0.9600
13:50018822:GGCTG:G	acceptor_gain	0.9600
13:50015349:G:GG	donor_gain	0.9500
13:50015348:A:AG	donor_gain	0.9400
13:50020206:T:TA	acceptor_gain	0.9100
13:50020207:GTCCT:G	acceptor_loss	0.9100
13:50018358:A:AG	acceptor_gain	0.9000
13:50018368:A:AG	acceptor_gain	0.8900
13:50018369:G:GG	acceptor_gain	0.8900
13:50016068:TCAG:T	donor_loss	0.8800
13:50016069:CAGG:C	donor_loss	0.8800
13:50016070:AG:A	donor_loss	0.8800

AlphaMissense

1791 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:50020302:T:C	F223L	0.984
13:50020304:T:A	F223L	0.984
13:50020304:T:G	F223L	0.984
13:50016026:T:C	F178S	0.981
13:50015665:T:C	F58L	0.979
13:50015667:T:A	F58L	0.979
13:50015667:T:G	F58L	0.979
13:50020219:T:A	V195D	0.977
13:50016020:T:C	L176P	0.976
13:50020225:T:A	I197K	0.973
13:50015585:T:C	L31S	0.972
13:50015519:T:C	L9S	0.970
13:50020303:T:C	F223S	0.970
13:50015691:A:C	R66S	0.969
13:50015691:A:T	R66S	0.969
13:50015719:T:C	F76L	0.968
13:50015721:T:A	F76L	0.968
13:50015721:T:G	F76L	0.968
13:50015755:T:C	F88L	0.968
13:50015757:C:A	F88L	0.968
13:50015757:C:G	F88L	0.968
13:50015683:T:C	F64L	0.967
13:50015685:T:A	F64L	0.967
13:50015685:T:G	F64L	0.967
13:50015539:T:C	F16L	0.964
13:50015541:C:A	F16L	0.964
13:50015541:C:G	F16L	0.964
13:50015641:T:C	F50L	0.964
13:50015643:T:A	F50L	0.964
13:50015643:T:G	F50L	0.964

dbSNP variants (sampled 300 via entrez): RS1000359371 (13:50016196 C>T), RS1000719955 (13:50016963 G>A), RS1000981201 (13:50018081 TCTC>T), RS1001200126 (13:50017892 T>C), RS1001626720 (13:50018129 G>A,T), RS1001652242 (13:50014725 A>C), RS1001767483 (13:50014538 TTAGTG>T), RS1002211397 (13:50016587 G>A,C), RS1002384214 (13:50016547 C>T), RS1003625226 (13:50014644 A>G), RS1004335239 (13:50013785 G>A), RS1004522000 (13:50017449 T>C), RS1004785262 (13:50017840 G>A,T), RS1005494733 (13:50019315 C>G), RS1005673583 (13:50018600 C>T)

Disease associations

OMIM: gene MIM:607947 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002647_101	Height	9.000000e-27
GCST004651_6	Aortic root size	2.000000e-15
GCST007847_106	Type 2 diabetes	5.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluorobutanesulfonic acid	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Coal	increases abundance, decreases expression	1
Dihydrotestosterone	increases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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