KCTD18

Summary

KCTD18 (potassium channel tetramerization domain containing 18, HGNC:26446) is a protein-coding gene on chromosome 2q33.1, encoding BTB/POZ domain-containing protein KCTD18 (Q6PI47).

Predicted to enable identical protein binding activity. Predicted to be involved in monoatomic ion transmembrane transport and protein homooligomerization.

Source: NCBI Gene 130535 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_152387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26446
Approved symbol	KCTD18
Name	potassium channel tetramerization domain containing 18
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31322, 6530404F10Rik, FLJ37818
Ensembl gene	ENSG00000155729
Ensembl biotype	protein_coding
Entrez	130535

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000359878, ENST00000409157, ENST00000447556, ENST00000468413, ENST00000478816, ENST00000894433, ENST00000894434, ENST00000968695

RefSeq mRNA: 4 — MANE Select: NM_152387 NM_001321547, NM_001321548, NM_001321550, NM_152387

CCDS: CCDS2330

Canonical transcript exons

ENST00000359878 — 7 exons

Exon	Start	End
ENSE00001401725	200493172	200493274
ENSE00001585835	200488958	200490616
ENSE00001819250	200509628	200510068
ENSE00003617411	200498891	200499084
ENSE00003624055	200504748	200504959
ENSE00003631786	200497753	200497847
ENSE00003653892	200506857	200507091

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 89.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7046 / max 34.9194, expressed in 1653 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33166	3.6470	1564
33167	1.0576	601

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	89.21	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.25	gold quality
tibia	UBERON:0000979	88.16	gold quality
palpebral conjunctiva	UBERON:0001812	88.09	gold quality
buccal mucosa cell	CL:0002336	87.52	silver quality
bronchial epithelial cell	CL:0002328	87.51	gold quality
monocyte	CL:0000576	86.82	gold quality
leukocyte	CL:0000738	86.54	gold quality
skin of hip	UBERON:0001554	86.43	gold quality
bronchus	UBERON:0002185	86.39	gold quality
islet of Langerhans	UBERON:0000006	85.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.37	gold quality
esophagus squamous epithelium	UBERON:0006920	84.51	gold quality
popliteal artery	UBERON:0002250	84.42	gold quality
tibial artery	UBERON:0007610	84.42	gold quality
parotid gland	UBERON:0001831	84.17	gold quality
epithelium of nasopharynx	UBERON:0001951	84.15	gold quality
pancreas	UBERON:0001264	83.79	gold quality
stromal cell of endometrium	CL:0002255	83.75	gold quality
nasal cavity mucosa	UBERON:0001826	83.66	gold quality
upper leg skin	UBERON:0004262	83.63	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.41	gold quality
lower esophagus	UBERON:0013473	83.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.35	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.34	gold quality
aorta	UBERON:0000947	83.28	gold quality
descending thoracic aorta	UBERON:0002345	83.20	gold quality
gastrocnemius	UBERON:0001388	83.05	gold quality
muscle of leg	UBERON:0001383	83.04	gold quality
body of pancreas	UBERON:0001150	83.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting KCTD18, 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-4425	100.00	67.59	1049
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-33A-3P	99.70	70.27	3362

Literature-anchored findings (GeneRIF, showing 1)

• A haplotype of 23 SNPs spanning 131.6 Kb shared by all affected members of 3 linked families with restless legs syndrome was identified. The shared candidate region covers 46.9 Kb over the potassium channel-related gene KCTD18 and exons 10-13 of SPATS2L. (PMID:23054586)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kctd18	ENSMUSG00000054770
rattus_norvegicus	Kctd18	ENSRNOG00000027091
drosophila_melanogaster	twz	FBGN0034636
caenorhabditis_elegans	F32B4.5	WBGENE00009315

Paralogs (13): KCTD1 (ENSG00000134504), KCTD14 (ENSG00000151364), KCTD15 (ENSG00000153885), KCTD6 (ENSG00000168301), KCTD19 (ENSG00000168676), KCTD12 (ENSG00000178695), KCTD4 (ENSG00000180332), KCTD16 (ENSG00000183775), KCTD8 (ENSG00000183783), KCTD21 (ENSG00000188997), KCNRG (ENSG00000198553), KCTD11 (ENSG00000213859), KCTD7 (ENSG00000243335)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD18 — Q6PI47 (reviewed: Q6PI47)

All UniProt accessions (1): Q6PI47

Isoforms (3)

UniProt ID	Names	Canonical?
Q6PI47-1	1	yes
Q6PI47-2	2
Q6PI47-3	3

RefSeq proteins (4): NP_001308476, NP_001308477, NP_001308479, NP_689600* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR045704	KCTD18_C	Domain

Pfam: PF02214, PF19321

UniProt features (15 total): sequence variant 4, splice variant 4, sequence conflict 2, region of interest 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PI47-F1	60.83	0.11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_PROTEIN_HOMOOLIGOMERIZATION, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, LEE_RECENT_THYMIC_EMIGRANT, GSE13522_WT_VS_IFNG_KO_SKIN_DN, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_DN, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, GOBP_PROTEIN_COMPLEX_OLIGOMERIZATION, HAND1_TARGET_GENES, HMG20B_TARGET_GENES, SKIL_TARGET_GENES, ZNF282_TARGET_GENES, ZNF711_TARGET_GENES, ZSCAN30_TARGET_GENES, MIR302C_5P

GO Biological Process (1): protein homooligomerization (GO:0051260)

GO Molecular Function (1): identical protein binding (GO:0042802)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein complex oligomerization	1
protein binding	1

Protein interactions and networks

STRING

580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD18	KCTD19	Q17RG1	603
KCTD18	KCTD20	Q7Z5Y7	591
KCTD18	SPATS2L	Q9NUQ6	554
KCTD18	C2orf69	Q8N8R5	505
KCTD18	TYW5	A2RUC4	503
KCTD18	KCTD14	Q9BQ13	479
KCTD18	KCTD11	Q693B1	478
KCTD18	L3HYPDH	Q96EM0	477
KCTD18	MINDY4	Q4G0A6	455
KCTD18	FAM228B	P0C875	443
KCTD18	FAM234A	Q9H0X4	438
KCTD18	TTC22	Q5TAA0	427
KCTD18	KCNMB1	P78475	426
KCTD18	KCNK17	Q96T54	425
KCTD18	KCTD2	Q14681	419

IntAct

18 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
CUL3	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
MAD2L1BP	KIF20A	psi-mi:“MI:0914”(association)	0.530
COPS6	KLHL18	psi-mi:“MI:0914”(association)	0.530
KCTD18	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
DDX39B	RBM33	psi-mi:“MI:0914”(association)	0.350
SLC39A7	AIP	psi-mi:“MI:0914”(association)	0.350
RBX1	OBSL1	psi-mi:“MI:0914”(association)	0.350
NTF3	HSPA5	psi-mi:“MI:0914”(association)	0.350
CEP89	MLLT3	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): KCTD18 (Reconstituted Complex), KCTD18 (Affinity Capture-MS), KCTD18 (Reconstituted Complex), KCTD18 (Affinity Capture-Western), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS), KCTD18 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2L7I0, A2VDP0, A2YX04, A5D979, B4FM28, B6SLJ0, D3ZVU1, F4I8S3, F4KFC7, F6UH96, G3X912, O01835, Q0J9J6, Q22557, Q24595, Q2HJG4, Q32LR5, Q38796, Q4KM91, Q53WJ1, Q5U3H2, Q65Z40, Q680Q4, Q6E3D5, Q6PI47, Q6Z8M8, Q700C2, Q7KW09, Q7XC57, Q7Y1C4, Q7Y1C5, Q7Z5K2, Q7ZXG4, Q801E2, Q8L840, Q8RY95, Q91W18, Q91ZX6, Q941B6, Q9BVC5

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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
Neddylation	5	12.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	11
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

1324 predictions. Top by Δscore:

Variant	Effect	Δscore
2:200493161:G:C	donor_gain	1.0000
2:200493173:T:TA	donor_gain	1.0000
2:200504844:AG:A	donor_gain	1.0000
2:200504851:T:TA	donor_gain	1.0000
2:200506852:TTTA:T	donor_loss	1.0000
2:200506853:TTACC:T	donor_loss	1.0000
2:200506854:TA:T	donor_loss	1.0000
2:200506856:C:T	donor_loss	1.0000
2:200506856:CCTGA:C	donor_gain	1.0000
2:200507087:TCCCT:T	acceptor_gain	1.0000
2:200507088:CCCT:C	acceptor_gain	1.0000
2:200507088:CCCTC:C	acceptor_gain	1.0000
2:200507089:CCTC:C	acceptor_gain	1.0000
2:200507090:CT:C	acceptor_gain	1.0000
2:200507092:C:CC	acceptor_gain	1.0000
2:200493170:A:C	donor_gain	0.9900
2:200493272:CAC:C	acceptor_gain	0.9900
2:200493275:C:CA	acceptor_loss	0.9900
2:200493276:T:C	acceptor_loss	0.9900
2:200498884:GACAT:G	donor_loss	0.9900
2:200498885:ACAT:A	donor_loss	0.9900
2:200498886:CATA:C	donor_loss	0.9900
2:200498887:ATAC:A	donor_loss	0.9900
2:200498888:TACCT:T	donor_loss	0.9900
2:200498889:A:T	donor_loss	0.9900
2:200499083:GC:G	acceptor_gain	0.9900
2:200499084:CC:C	acceptor_gain	0.9900
2:200499085:C:CC	acceptor_gain	0.9900
2:200504878:T:C	donor_gain	0.9900
2:200504957:CCC:C	acceptor_gain	0.9900

AlphaMissense

2748 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:200504846:C:G	A92P	0.998
2:200506904:A:G	L38S	0.997
2:200499030:A:G	W143R	0.996
2:200499030:A:T	W143R	0.996
2:200504845:G:T	A92D	0.996
2:200504857:A:G	L88P	0.996
2:200504905:A:G	L72P	0.996
2:200506879:A:C	F46L	0.996
2:200506879:A:T	F46L	0.996
2:200506881:A:G	F46L	0.996
2:200506891:G:C	F42L	0.996
2:200506891:G:T	F42L	0.996
2:200506893:A:G	F42L	0.996
2:200504835:A:C	F95L	0.995
2:200504835:A:T	F95L	0.995
2:200504837:A:G	F95L	0.995
2:200504926:A:G	F65S	0.995
2:200506892:A:G	F42S	0.995
2:200506928:A:G	L30S	0.995
2:200506970:A:G	L16P	0.995
2:200497772:A:C	F214L	0.994
2:200497772:A:T	F214L	0.994
2:200497774:A:G	F214L	0.994
2:200499023:A:G	L145P	0.994
2:200504800:A:G	L107S	0.994
2:200504925:A:C	F65L	0.994
2:200504925:A:T	F65L	0.994
2:200504927:A:G	F65L	0.994
2:200506880:A:G	F46S	0.994
2:200506943:G:T	A25D	0.994

dbSNP variants (sampled 300 via entrez): RS1000010238 (2:200496621 A>G), RS1000061023 (2:200496974 T>C), RS1000191005 (2:200491894 T>C), RS1000241605 (2:200505359 T>G), RS1000249403 (2:200496279 G>A), RS1000589129 (2:200503934 A>C), RS1000708551 (2:200509929 G>A), RS1000760916 (2:200510076 T>C), RS1001230096 (2:200509951 C>A,T), RS1001468371 (2:200495937 T>A,G), RS1001497259 (2:200510637 A>G), RS1001759357 (2:200504365 A>T), RS1001935269 (2:200509864 G>A,C), RS1002001448 (2:200511040 A>G), RS1002204689 (2:200510667 T>C)

Disease associations

OMIM: gene `` | 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
GCST003226_12	Pelvic organ prolapse	3.000000e-06
GCST003254_6	Urinary albumin-to-creatinine ratio in non-diabetics	9.000000e-06
GCST009391_1713	Metabolite levels	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio
EFO:0010341	cholesteryl ester 16:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
sodium arsenite	affects expression, decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Oxyquinoline	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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