KCTD2

Summary

KCTD2 (potassium channel tetramerization domain containing 2, HGNC:21294) is a protein-coding gene on chromosome 17q25.1, encoding BTB/POZ domain-containing protein KCTD2 (Q14681).

Predicted to enable cullin family protein binding activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be part of Cul3-RING ubiquitin ligase complex. Predicted to be active in cytoplasm.

Source: NCBI Gene 23510 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 38 total
• MANE Select transcript: NM_015353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21294
Approved symbol	KCTD2
Name	potassium channel tetramerization domain containing 2
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0176
Ensembl gene	ENSG00000180901
Ensembl biotype	protein_coding
OMIM	613422
Entrez	23510

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding_CDS_not_defined, 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000322444, ENST00000375286, ENST00000577516, ENST00000579230, ENST00000579242, ENST00000581589, ENST00000582840, ENST00000584570, ENST00000584767

RefSeq mRNA: 1 — MANE Select: NM_015353 NM_015353

CCDS: CCDS32728

Canonical transcript exons

ENST00000322444 — 6 exons

Exon	Start	End
ENSE00001291534	75047225	75047589
ENSE00001307943	75063018	75065886
ENSE00003520716	75049220	75049328
ENSE00003569482	75059510	75059605
ENSE00003587456	75062120	75062245
ENSE00003694707	75053014	75053105

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4625 / max 201.0157, expressed in 1794 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162690	9.7257	1783
162689	1.3616	988
162688	0.1986	80
162687	0.1766	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	98.20	gold quality
cerebellar cortex	UBERON:0002129	98.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.00	gold quality
cerebellum	UBERON:0002037	97.82	gold quality
paraflocculus	UBERON:0005351	96.83	gold quality
cerebellar vermis	UBERON:0004720	94.94	gold quality
right frontal lobe	UBERON:0002810	94.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.06	gold quality
prefrontal cortex	UBERON:0000451	93.42	gold quality
cingulate cortex	UBERON:0003027	93.37	gold quality
anterior cingulate cortex	UBERON:0009835	93.32	gold quality
spinal cord	UBERON:0002240	93.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.14	gold quality
oocyte	CL:0000023	93.08	gold quality
frontal cortex	UBERON:0001870	92.45	gold quality
neocortex	UBERON:0001950	92.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.37	gold quality
amygdala	UBERON:0001876	92.23	gold quality
gastrocnemius	UBERON:0001388	92.13	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.02	gold quality
right testis	UBERON:0004534	91.92	gold quality
muscle of leg	UBERON:0001383	91.64	gold quality
left testis	UBERON:0004533	91.60	gold quality
nucleus accumbens	UBERON:0001882	91.51	gold quality
middle temporal gyrus	UBERON:0002771	91.42	gold quality
central nervous system	UBERON:0001017	91.40	gold quality
brain	UBERON:0000955	91.35	gold quality
cerebral cortex	UBERON:0000956	91.18	gold quality
putamen	UBERON:0001874	91.01	gold quality
telencephalon	UBERON:0001893	90.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.46
E-GEOD-100618	no	222.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting KCTD2, 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-4283	100.00	66.42	2097
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111

Literature-anchored findings (GeneRIF, showing 2)

• By merging results of a meta-GWAS, results in the CHARGE consortium data sets and an in vivo genotyping comprising 4501 individuals, detected a novel locus ATP5H/KCTD2 associated with Alzheimer’s disease risk (PMID:23857120)
• KCTD Proteins Have Redundant Functions in Controlling Cellular Growth. (PMID:38732215)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kctd2	ENSDARG00000025875
mus_musculus	Kctd2	ENSMUSG00000016940
rattus_norvegicus	Kctd2	ENSRNOG00000023764
drosophila_melanogaster	inc	FBGN0025394
caenorhabditis_elegans		WBGENE00016871

Paralogs (3): KCTD17 (ENSG00000100379), KCTD9 (ENSG00000104756), KCTD5 (ENSG00000167977)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD2 — Q14681 (reviewed: Q14681)

Alternative names: Potassium channel tetramerization domain-containing protein 2

All UniProt accessions (3): Q14681, H0Y3B9, J3QSC8

UniProt curated annotations — full annotation on UniProt →

RefSeq proteins (1): NP_056168* (*=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 (10 total): compositionally biased region 3, modified residue 2, initiator methionine 1, chain 1, domain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14681-F1	75.36	0.44

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 (2): 2, 33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, LIAO_METASTASIS, GOBP_PROTEIN_HOMOOLIGOMERIZATION, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_PROTEIN_CATABOLIC_PROCESS, PARENT_MTOR_SIGNALING_UP, NUYTTEN_EZH2_TARGETS_DN, GOCC_TRANSFERASE_COMPLEX, GRYDER_PAX3FOXO1_TOP_ENHANCERS, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOBP_PROTEOLYSIS, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX

GO Biological Process (2): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein homooligomerization (GO:0051260)

GO Molecular Function (3): protein-containing complex binding (GO:0044877), cullin family protein binding (GO:0097602), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), Cul3-RING ubiquitin ligase complex (GO:0031463)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein complex oligomerization	1
protein binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

3081 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD2	CUL3	Q13618	754
KCTD2	ATP5PD	O75947	701
KCTD2	KCTD11	Q693B1	581
KCTD2	KLHL18	O94889	532
KCTD2	ARMC7	Q9H6L4	527
KCTD2	KCTD20	Q7Z5Y7	466
KCTD2	BTBD10	Q9BSF8	466
KCTD2	KCTD19	Q17RG1	458
KCTD2	ANKFY1	Q9P2R3	457
KCTD2	BTBD7	Q9P203	454
KCTD2	NT5C	Q8TCD5	437
KCTD2	SUMO2	P55855	420
KCTD2	KCTD18	Q6PI47	419
KCTD2	SLC16A5	O15375	410
KCTD2	KCTD17	Q8N5Z5	404

IntAct

58 interactions, top by confidence:

A	B	Type	Score
KLHL12	KLHL2	psi-mi:“MI:0914”(association)	0.850
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
TNFSF14	TMEM11	psi-mi:“MI:0914”(association)	0.670
TFAP4	ANGPTL7	psi-mi:“MI:0914”(association)	0.640
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
GNG8	GNB5	psi-mi:“MI:0914”(association)	0.640
GLRA3	KCTD2	psi-mi:“MI:0915”(physical association)	0.560
GLRA3	KCTD2	psi-mi:“MI:0914”(association)	0.560
MIS12	SPC24	psi-mi:“MI:0914”(association)	0.530
SMC1A	PDS5B	psi-mi:“MI:0914”(association)	0.530
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
TMEM255A	WWP2	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
KCND2	BAG3	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
GNG2	GNB5	psi-mi:“MI:0914”(association)	0.530
Kctd5	CKAP5	psi-mi:“MI:0915”(physical association)	0.400
KCTD2	POLK	psi-mi:“MI:0915”(physical association)	0.400
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
Kctd5		psi-mi:“MI:0914”(association)	0.350
DLG3	WDR91	psi-mi:“MI:0914”(association)	0.350
HUWE1	NCOA4	psi-mi:“MI:0914”(association)	0.350
ORF21	USP9Y	psi-mi:“MI:0914”(association)	0.350

BioGRID (95): KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS), KCTD2 (Two-hybrid), CUL3 (Affinity Capture-Western), MYC (Affinity Capture-Western), KCTD2 (Affinity Capture-Western), KCTD2 (Affinity Capture-MS), KCTD2 (Affinity Capture-MS)

ESM2 similar proteins: A3KMV1, A4IFB4, A5PKG7, B1WC97, B5DEL1, D5SHR0, O35260, O43147, O70479, P0C5J9, P59438, Q0VD00, Q0VFV7, Q13829, Q14681, Q28DC9, Q29RJ0, Q2HJ48, Q2T9W0, Q2TUM3, Q3URF8, Q4G0X4, Q5F3E8, Q5M956, Q5RBH4, Q5XJ34, Q5ZJP7, Q6DC02, Q6DCX3, Q6DK85, Q6P3P4, Q6P7W2, Q6PI47, Q719H9, Q7TNY1, Q80TM9, Q80U12, Q811L6, Q863D4, Q8BGV7

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 69 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
Resolution of Sister Chromatid Cohesion	5	11.1×	3e-03
Separation of Sister Chromatids	5	7.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1813 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75039061:CAT:C	acceptor_gain	1.0000
17:75039064:C:CC	acceptor_gain	1.0000
17:75039064:C:T	acceptor_loss	1.0000
17:75039065:T:A	acceptor_loss	1.0000
17:75039671:C:CT	donor_gain	1.0000
17:75039672:T:TT	donor_gain	1.0000
17:75040090:A:AC	donor_gain	1.0000
17:75040091:C:CC	donor_gain	1.0000
17:75040091:CAT:C	donor_gain	1.0000
17:75040164:C:CC	acceptor_gain	1.0000
17:75042178:CA:C	donor_loss	1.0000
17:75042179:A:AC	donor_gain	1.0000
17:75042179:A:C	donor_loss	1.0000
17:75042180:C:CC	donor_gain	1.0000
17:75042180:CCTT:C	donor_gain	1.0000
17:75042273:CCAAC:C	acceptor_gain	1.0000
17:75042274:CAAC:C	acceptor_gain	1.0000
17:75042274:CAACC:C	acceptor_gain	1.0000
17:75042275:AAC:A	acceptor_gain	1.0000
17:75042276:AC:A	acceptor_gain	1.0000
17:75042277:CC:C	acceptor_gain	1.0000
17:75042278:C:CC	acceptor_gain	1.0000
17:75042278:CTG:C	acceptor_loss	1.0000
17:75042279:T:G	acceptor_loss	1.0000
17:75042283:C:CT	acceptor_gain	1.0000
17:75042283:C:T	acceptor_gain	1.0000
17:75042285:C:CT	acceptor_gain	1.0000
17:75042286:A:T	acceptor_gain	1.0000
17:75049211:G:A	acceptor_gain	1.0000
17:75049218:A:AG	acceptor_gain	1.0000

AlphaMissense

1688 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75047467:T:A	W73R	1.000
17:75047467:T:C	W73R	1.000
17:75047469:G:C	W73C	1.000
17:75047469:G:T	W73C	1.000
17:75047477:T:A	L76Q	1.000
17:75047477:T:C	L76P	1.000
17:75047481:C:A	N77K	1.000
17:75047481:C:G	N77K	1.000
17:75047482:G:A	V78M	1.000
17:75047483:T:A	V78E	1.000
17:75047485:G:A	G79R	1.000
17:75047485:G:C	G79R	1.000
17:75047486:G:A	G79E	1.000
17:75047486:G:T	G79V	1.000
17:75047488:G:C	G80R	1.000
17:75047488:G:T	G80C	1.000
17:75047489:G:A	G80D	1.000
17:75047489:G:T	G80V	1.000
17:75047497:T:C	F83L	1.000
17:75047498:T:C	F83S	1.000
17:75047498:T:G	F83C	1.000
17:75047499:C:A	F83L	1.000
17:75047499:C:G	F83L	1.000
17:75047504:C:T	T85I	1.000
17:75047507:C:T	T86I	1.000
17:75047519:T:C	L90S	1.000
17:75047536:T:C	S96P	1.000
17:75047539:T:C	F97L	1.000
17:75047540:T:C	F97S	1.000
17:75047540:T:G	F97C	1.000

dbSNP variants (sampled 300 via entrez): RS1000112682 (17:75051978 A>G), RS1000115515 (17:75033624 C>G), RS1000204754 (17:75043094 C>T), RS1000353180 (17:75062564 G>A,C), RS1000438449 (17:75057370 T>C), RS1000486566 (17:75042836 G>C), RS1000516486 (17:75035603 G>A), RS1000523350 (17:75060159 A>G), RS1000529733 (17:75033781 C>G), RS1000534448 (17:75035237 G>A,C), RS1000537240 (17:75044945 G>T), RS1000588131 (17:75035401 C>G,T), RS1000646216 (17:75038300 G>A,T), RS1000719366 (17:75050647 G>C), RS1000785777 (17:75052046 T>C)

Disease associations

OMIM: gene MIM:613422 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000905_9	Information processing speed	8.000000e-06
GCST003264_818	Post bronchodilator FEV1/FVC ratio	8.000000e-07
GCST003423_1	Alzheimer’s disease or small vessel stroke	2.000000e-08
GCST008103_113	Bipolar disorder	4.000000e-06
GCST90002388_507	Lymphocyte count	3.000000e-16
GCST90002389_242	Lymphocyte percentage of white cells	4.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004363	information processing speed
EFO:0004713	FEV/FVC ratio
EFO:1001504	small vessel stroke
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
propylparaben	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
beta-methylcholine	affects expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Leflunomide	decreases expression	1
Carbamazepine	affects expression	1
Lead	affects expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Vitamin E	increases expression	1
Cadmium Chloride	decreases expression	1
Genistein	decreases expression	1

Clinical trials (associated diseases)

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