KCTD9

Summary

KCTD9 (potassium channel tetramerization domain containing 9, HGNC:22401) is a protein-coding gene on chromosome 8p21.2, encoding BTB/POZ domain-containing protein KCTD9 (Q7L273). Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of target proteins, leading to their degradation by the proteasome.

Enables cullin family protein binding activity and identical protein binding activity. Predicted to be involved in intracellular signal transduction; protein homooligomerization; and protein ubiquitination. Predicted to act upstream of or within several processes, including NK T cell lineage commitment; natural killer cell activation; and response to virus.

Source: NCBI Gene 54793 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_017634

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22401
Approved symbol	KCTD9
Name	potassium channel tetramerization domain containing 9
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20038, BTBD27
Ensembl gene	ENSG00000104756
Ensembl biotype	protein_coding
OMIM	617265
Entrez	54793

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding_CDS_not_defined, 3 retained_intron, 2 protein_coding, 2 nonsense_mediated_decay

ENST00000221200, ENST00000517914, ENST00000518067, ENST00000518997, ENST00000519665, ENST00000520405, ENST00000521458, ENST00000522493, ENST00000523140, ENST00000523294, ENST00000524217, ENST00000710397

RefSeq mRNA: 1 — MANE Select: NM_017634 NM_017634

CCDS: CCDS6048

Canonical transcript exons

ENST00000221200 — 12 exons

Exon	Start	End
ENSE00000818559	25427847	25429973
ENSE00001745055	25458199	25458433
ENSE00003469667	25436235	25436330
ENSE00003478710	25436418	25436485
ENSE00003481384	25439606	25439664
ENSE00003490005	25435363	25435512
ENSE00003523415	25439279	25439407
ENSE00003536909	25432504	25432637
ENSE00003551616	25433330	25433435
ENSE00003655532	25446129	25446250
ENSE00003669990	25440577	25440673
ENSE00003689266	25444292	25444335

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 95.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0078 / max 108.7232, expressed in 1658 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92405	6.0078	1658

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	95.45	gold quality
jejunal mucosa	UBERON:0000399	94.55	gold quality
descending thoracic aorta	UBERON:0002345	94.41	gold quality
tibial nerve	UBERON:0001323	94.32	gold quality
calcaneal tendon	UBERON:0003701	93.98	gold quality
sural nerve	UBERON:0015488	93.91	gold quality
tibial artery	UBERON:0007610	93.75	gold quality
popliteal artery	UBERON:0002250	93.74	gold quality
heart right ventricle	UBERON:0002080	93.72	gold quality
aorta	UBERON:0000947	93.70	gold quality
thoracic aorta	UBERON:0001515	93.67	gold quality
ascending aorta	UBERON:0001496	93.56	gold quality
artery	UBERON:0001637	93.43	gold quality
mucosa of stomach	UBERON:0001199	93.05	gold quality
oocyte	CL:0000023	93.04	gold quality
rectum	UBERON:0001052	92.86	gold quality
right coronary artery	UBERON:0001625	92.54	gold quality
left coronary artery	UBERON:0001626	92.37	gold quality
heart left ventricle	UBERON:0002084	92.12	gold quality
cardiac ventricle	UBERON:0002082	92.09	gold quality
coronary artery	UBERON:0001621	91.69	gold quality
heart	UBERON:0000948	91.49	gold quality
secondary oocyte	CL:0000655	91.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.05	gold quality
lower esophagus	UBERON:0013473	91.04	gold quality
penis	UBERON:0000989	91.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.89	gold quality
colonic epithelium	UBERON:0000397	90.76	gold quality
esophagus	UBERON:0001043	90.74	gold quality
right atrium auricular region	UBERON:0006631	90.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

204 targeting KCTD9, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 3)

• The increased expression of potassium channel gene KCTD9 correlates with disease severity in patients with viral hepatitis B. (PMID:19032868)
• These results suggest the involvement of KCTD9 in NK cell activation and provide additional insight into a potential therapeutic target for molecular manipulation for hepatitis B virus-induced acute-on-chronic liver failure patients (PMID:23376586)
• The authors find that the KCTD proteins 5, 6, 9 and 17 bind to Cul3 with high affinity, while the KCTD proteins 1 and 16 do not have detectable binding. (PMID:26334369)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kctd9b	ENSDARG00000010603
danio_rerio	kctd9a	ENSDARG00000021209
mus_musculus	Kctd9	ENSMUSG00000034327
rattus_norvegicus	Kctd9	ENSRNOG00000012951
drosophila_melanogaster	CG14647	FBGN0037244

Paralogs (3): KCTD17 (ENSG00000100379), KCTD5 (ENSG00000167977), KCTD2 (ENSG00000180901)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD9 — Q7L273 (reviewed: Q7L273)

All UniProt accessions (4): A0AA34QVI4, Q7L273, K7ENB5, K7EQN1

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of target proteins, leading to their degradation by the proteasome.

Subunit / interactions. Forms pentamers. Component of a complex composed of 5 subunits of KCTD9 and 5 CUL3.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_060104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR001646	5peptide_repeat	Repeat
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR021789	KHA_dom	Domain
IPR036572	Doublecortin_dom_sf	Homologous_superfamily
IPR051082	Pentapeptide-BTB/POZ_domain	Family

Pfam: PF00805, PF02214, PF11834

UniProt features (18 total): domain 5, helix 5, strand 3, chain 1, turn 1, modified residue 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5BXH	X-RAY DIFFRACTION	2.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L273-F1	89.67	0.73

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 11

Mutagenesis-validated functional residues (1):

Position	Phenotype
125	impaired interaction with cul3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, ATGCAGT_MIR217, GGGTGGRR_PAX4_03, CATTTCA_MIR203, chr8p21, FISCHER_G2_M_CELL_CYCLE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, AACTTT_UNKNOWN, GOBP_PROTEIN_HOMOOLIGOMERIZATION, FISCHER_DREAM_TARGETS, LEIN_MIDBRAIN_MARKERS, MARSON_BOUND_BY_E2F4_UNSTIMULATED, AAGCACA_MIR218, GOMF_CULLIN_FAMILY_PROTEIN_BINDING, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A

GO Biological Process (3): protein ubiquitination (GO:0016567), intracellular signal transduction (GO:0035556), protein homooligomerization (GO:0051260)

GO Molecular Function (3): identical protein binding (GO:0042802), cullin family protein binding (GO:0097602), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
protein modification by small protein conjugation	1
intracellular anatomical structure	1
signal transduction	1
protein complex oligomerization	1
binding	1

Protein interactions and networks

STRING

1182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD9	KCTD1	Q719H9	697
KCTD9	KCTD11	Q693B1	646
KCTD9	CUL3	Q13618	596
KCTD9	LDAF1	Q96B96	518
KCTD9	KCTD19	Q17RG1	514
KCTD9	TMEM144	Q7Z5S9	485
KCTD9	ANKRD9	Q96BM1	482
KCTD9	PPP1R16B	Q96T49	480
KCTD9	CLRN3	Q8NCR9	474
KCTD9	UBOX5	O94941	472
KCTD9	RNF24	Q9Y225	463
KCTD9	ARL13A	Q5H913	462
KCTD9	LZIC	Q8WZA0	462
KCTD9	IWS1	Q96ST2	461
KCTD9	KCTD20	Q7Z5Y7	437

IntAct

364 interactions, top by confidence:

A	B	Type	Score
CUL3	KCTD9	psi-mi:“MI:0915”(physical association)	0.870
KCTD9	NUP35	psi-mi:“MI:0915”(physical association)	0.870
NUP35	KCTD9	psi-mi:“MI:0915”(physical association)	0.870
NUP35	KCTD9	psi-mi:“MI:0914”(association)	0.870
NRP1	CSNK2A2	psi-mi:“MI:0914”(association)	0.790
GORASP2	KCTD9	psi-mi:“MI:0915”(physical association)	0.780
KCTD9	GORASP2	psi-mi:“MI:0915”(physical association)	0.780
KCTD9	TRIM42	psi-mi:“MI:0915”(physical association)	0.720
SDCBP	KCTD9	psi-mi:“MI:0915”(physical association)	0.720
PSMA1	KCTD9	psi-mi:“MI:0915”(physical association)	0.720
KCTD9	GEM	psi-mi:“MI:0915”(physical association)	0.720
KCTD9	LONRF1	psi-mi:“MI:0915”(physical association)	0.720
KCTD9	SYT6	psi-mi:“MI:0915”(physical association)	0.720
TRIM27	KCTD9	psi-mi:“MI:0915”(physical association)	0.720
TRIM32	KCTD9	psi-mi:“MI:0915”(physical association)	0.720
KCTD9	CBX8	psi-mi:“MI:0915”(physical association)	0.720
TRIM42	KCTD9	psi-mi:“MI:0915”(physical association)	0.720
GEM	KCTD9	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (265): KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid), KCTD9 (Two-hybrid)

ESM2 similar proteins: A0A3L7I2I8, A7MB89, D3Z7A5, O60733, P27612, P97443, P97570, P97819, Q28FE4, Q2T9K6, Q32KM6, Q32KU3, Q32LL6, Q3MHE2, Q4QQN5, Q4R3N2, Q4R842, Q4VBJ9, Q502X0, Q5IH13, Q5IH14, Q5NVD0, Q5PPV3, Q5RF15, Q5VZ52, Q66H07, Q6B858, Q6DHG0, Q6PF18, Q6UL01, Q6VTH5, Q7L273, Q80UN1, Q8C5T4, Q8CEF1, Q8NB12, Q8TAM2, Q8TC84, Q90WG6, Q91ZN7

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 95 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
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	21.6×	9e-04
KEAP1-NFE2L2 pathway	6	13.6×	9e-04
Antigen processing: Ubiquitination & Proteasome degradation	8	5.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1904 predictions. Top by Δscore:

Variant	Effect	Δscore
8:25429969:CAATT:C	acceptor_gain	1.0000
8:25429972:TT:T	acceptor_gain	1.0000
8:25429974:C:CC	acceptor_gain	1.0000
8:25431692:AGG:A	donor_gain	1.0000
8:25431692:AGGC:A	donor_gain	1.0000
8:25433325:CTCA:C	donor_loss	1.0000
8:25433326:TCA:T	donor_loss	1.0000
8:25433329:CCTT:C	donor_gain	1.0000
8:25433431:GCACA:G	acceptor_gain	1.0000
8:25433432:CACA:C	acceptor_gain	1.0000
8:25433432:CACAC:C	acceptor_gain	1.0000
8:25433433:ACA:A	acceptor_gain	1.0000
8:25433434:CA:C	acceptor_gain	1.0000
8:25433434:CAC:C	acceptor_gain	1.0000
8:25433436:C:CC	acceptor_gain	1.0000
8:25435357:A:AC	donor_gain	1.0000
8:25435358:C:CC	donor_gain	1.0000
8:25435358:CTTA:C	donor_gain	1.0000
8:25435359:TTA:T	donor_loss	1.0000
8:25435360:TA:T	donor_loss	1.0000
8:25435361:A:AC	donor_gain	1.0000
8:25435361:ACGT:A	donor_gain	1.0000
8:25435362:C:CA	donor_gain	1.0000
8:25435362:CG:C	donor_gain	1.0000
8:25435362:CGT:C	donor_gain	1.0000
8:25435362:CGTC:C	donor_gain	1.0000
8:25435362:CGTCA:C	donor_gain	1.0000
8:25435508:AAACC:A	acceptor_gain	1.0000
8:25435509:AACC:A	acceptor_gain	1.0000
8:25435510:ACC:A	acceptor_gain	1.0000

AlphaMissense

2541 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:25429875:C:A	M384I	1.000
8:25429875:C:G	M384I	1.000
8:25429875:C:T	M384I	1.000
8:25429876:A:G	M384T	1.000
8:25429924:G:A	S368F	1.000
8:25429924:G:T	S368Y	1.000
8:25429927:C:A	G367V	1.000
8:25429927:C:T	G367E	1.000
8:25429928:C:A	G367W	1.000
8:25429928:C:G	G367R	1.000
8:25429928:C:T	G367R	1.000
8:25429929:T:A	R366S	1.000
8:25429929:T:G	R366S	1.000
8:25429930:C:A	R366I	1.000
8:25429930:C:G	R366T	1.000
8:25429933:A:C	L365R	1.000
8:25429933:A:G	L365P	1.000
8:25429933:A:T	L365Q	1.000
8:25429935:G:C	N364K	1.000
8:25429935:G:T	N364K	1.000
8:25429939:G:T	A363D	1.000
8:25429940:C:G	A363P	1.000
8:25429948:A:C	L360R	1.000
8:25429948:A:G	L360P	1.000
8:25429948:A:T	L360H	1.000
8:25429951:T:C	D359G	1.000
8:25429953:A:C	C358W	1.000
8:25429954:C:T	C358Y	1.000
8:25429955:A:G	C358R	1.000
8:25429957:C:T	G357E	1.000

dbSNP variants (sampled 300 via entrez): RS1000194807 (8:25446958 T>C), RS1000220720 (8:25449328 C>G), RS1000367179 (8:25440213 T>C), RS1000528376 (8:25445103 G>A), RS1000684346 (8:25432094 T>C), RS1000770351 (8:25431267 A>C,G), RS1000967824 (8:25439092 T>G), RS1000969149 (8:25451339 G>T), RS1001230489 (8:25430928 C>A,T), RS1001344688 (8:25457355 T>C), RS1001385802 (8:25457942 G>A,T), RS1001458845 (8:25457782 T>C), RS1001482889 (8:25444858 G>A), RS1001490097 (8:25457660 GA>G), RS1001604041 (8:25433621 A>G)

Disease associations

OMIM: gene MIM:617265 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002388_239	Lymphocyte count	8.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression, affects binding, decreases reaction	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
deguelin	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Cisplatin	increases expression	1
Coumestrol	increases expression	1
Diethylstilbestrol	decreases expression	1
Endosulfan	decreases expression	1
Naled	affects expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Phenobarbital	affects expression	1
Dihydrotestosterone	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	increases expression	1

Clinical trials (associated diseases)

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