KCTD4

Summary

KCTD4 (potassium channel tetramerization domain containing 4, HGNC:23227) is a protein-coding gene on chromosome 13q14.12-q14.13, encoding BTB/POZ domain-containing protein KCTD4 (Q8WVF5).

Predicted to enable identical protein binding activity. Predicted to be involved in protein homooligomerization.

Source: NCBI Gene 386618 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_198404

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23227
Approved symbol	KCTD4
Name	potassium channel tetramerization domain containing 4
Location	13q14.12-q14.13
Locus type	gene with protein product
Status	Approved
Aliases	bA321C24.3
Ensembl gene	ENSG00000180332
Ensembl biotype	protein_coding
OMIM	620638
Entrez	386618

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000379108

RefSeq mRNA: 1 — MANE Select: NM_198404 NM_198404

CCDS: CCDS9396

Canonical transcript exons

ENST00000379108 — 2 exons

Exon	Start	End
ENSE00001479791	45192853	45194754
ENSE00003920564	45200824	45201045

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 93.13.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8759 / max 271.3708, expressed in 351 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137076	0.9352	170
137081	0.3283	148
137077	0.2336	91
137080	0.2038	97
137078	0.1003	46
207023	0.0439	9
137079	0.0308	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.13	gold quality
nucleus accumbens	UBERON:0001882	92.16	gold quality
amygdala	UBERON:0001876	87.84	gold quality
caudate nucleus	UBERON:0001873	86.51	gold quality
temporal lobe	UBERON:0001871	84.42	gold quality
cartilage tissue	UBERON:0002418	84.04	gold quality
middle temporal gyrus	UBERON:0002771	82.80	gold quality
Ammon’s horn	UBERON:0001954	82.60	gold quality
putamen	UBERON:0001874	82.27	gold quality
entorhinal cortex	UBERON:0002728	80.80	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.92	gold quality
endothelial cell	CL:0000115	79.37	gold quality
prefrontal cortex	UBERON:0000451	79.13	gold quality
corpus callosum	UBERON:0002336	78.70	gold quality
amniotic fluid	UBERON:0000173	78.62	gold quality
tibia	UBERON:0000979	78.55	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.24	gold quality
forebrain	UBERON:0001890	77.26	gold quality
hypothalamus	UBERON:0001898	76.84	gold quality
epithelial cell of pancreas	CL:0000083	76.77	gold quality
anterior cingulate cortex	UBERON:0009835	76.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.06	gold quality
cerebral cortex	UBERON:0000956	76.04	gold quality
frontal cortex	UBERON:0001870	75.77	gold quality
neocortex	UBERON:0001950	74.71	gold quality
trigeminal ganglion	UBERON:0001675	74.70	gold quality
right frontal lobe	UBERON:0002810	74.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.85	gold quality
pigmented layer of retina	UBERON:0001782	73.36	gold quality
tibial nerve	UBERON:0001323	73.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting KCTD4, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-579-3P	99.86	71.66	3628

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kctd4	ENSDARG00000068691
mus_musculus	Kctd4	ENSMUSG00000046523
rattus_norvegicus	Kctd4	ENSRNOG00000050996
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), KCTD16 (ENSG00000183775), KCTD8 (ENSG00000183783), KCTD21 (ENSG00000188997), KCNRG (ENSG00000198553), KCTD11 (ENSG00000213859), KCTD7 (ENSG00000243335)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD4 — Q8WVF5 (reviewed: Q8WVF5)

All UniProt accessions (1): Q8WVF5

RefSeq proteins (1): NP_940686* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR045740	KCTD4_C	Domain

Pfam: PF02214, PF19323

UniProt features (4 total): 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-Q8WVF5-F1	81.52	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): FREAC3_01, RIGGI_EWING_SARCOMA_PROGENITOR_DN, NKX25_01, AACTTT_UNKNOWN, IK2_01, GOBP_PROTEIN_HOMOOLIGOMERIZATION, LEF1_Q6, WHN_B, AML1_01, FOX_Q2, chr13q14, YATGNWAAT_OCT_C, PR_01, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_DN, MARTENS_TRETINOIN_RESPONSE_UP

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

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein complex oligomerization	1
protein binding	1
binding	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD4	CBY2	Q8NA61	605
KCTD4	GTF2F2	P13984	551
KCTD4	LDB2	O43679	482
KCTD4	KCTD20	Q7Z5Y7	466
KCTD4	GIGYF2	Q6Y7W6	426
KCTD4	WDFY2	Q96P53	412
KCTD4	TULP2	O00295	402
KCTD4	PROSER2	Q86WR7	401
KCTD4	KIAA1191	Q96A73	394
KCTD4	BTBD19	C9JJ37	389
KCTD4	FAM43B	Q6ZT52	359
KCTD4	BTBD10	Q9BSF8	347
KCTD4	KLHL34	Q8N239	340
KCTD4	HTR2A	P28223	339
KCTD4	GGA1	Q9UJY5	339

IntAct

28 interactions, top by confidence:

A	B	Type	Score
EFHC1	KCTD4	psi-mi:“MI:0915”(physical association)	0.720
TAE1	KCTD4	psi-mi:“MI:0915”(physical association)	0.560
SRP1	KCTD4	psi-mi:“MI:0915”(physical association)	0.560
KCTD4	TAE1	psi-mi:“MI:0915”(physical association)	0.560
KCTD4	SRP1	psi-mi:“MI:0915”(physical association)	0.560
KCTD4	DAXX	psi-mi:“MI:0915”(physical association)	0.560
KCTD4	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
KCTD4	KCTD4	psi-mi:“MI:0915”(physical association)	0.550
KCTD4	FER	psi-mi:“MI:0915”(physical association)	0.490
KCTD4	TNS4	psi-mi:“MI:0915”(physical association)	0.370
FXR2	KCTD4	psi-mi:“MI:0915”(physical association)	0.370
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
DAXX	KCTD4	psi-mi:“MI:0915”(physical association)	0.000
EFHC1	KCTD4	psi-mi:“MI:0915”(physical association)	0.000
NTAQ1	KCTD4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), KCTD4 (Affinity Capture-Western), KCTD4 (Proximity Label-MS), KCTD4 (Two-hybrid), KCTD4 (Two-hybrid), DAXX (Two-hybrid), KCTD4 (Affinity Capture-MS), KCTD4 (Affinity Capture-MS)

ESM2 similar proteins: A1A5R8, A6H6X4, A9ULR9, B1WC97, B8JKF4, O15091, O70479, P93002, Q0VFV7, Q12259, Q13829, Q28DC9, Q2HJ48, Q2T9W0, Q3TUL7, Q3URF8, Q4G0X4, Q5EAX2, Q5F3E8, Q5H9S7, Q5M956, Q5R4M2, Q5RBH4, Q5RD58, Q5XJ34, Q5ZJP7, Q68FF0, Q6DC02, Q6DCX3, Q6DFW0, Q6DG99, Q6NSI8, Q6P3P4, Q719H9, Q7TNY1, Q7TPL3, Q8BJK1, Q8BNL5, Q8NC69, Q8R4G8

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

211 predictions. Top by Δscore:

Variant	Effect	Δscore
13:45199942:G:GT	donor_gain	0.9700
13:45194395:A:T	donor_gain	0.8500
13:45195339:A:AC	acceptor_gain	0.8200
13:45193040:G:GA	donor_gain	0.8000
13:45195336:CTTA:C	acceptor_gain	0.7900
13:45195340:A:G	acceptor_gain	0.7900
13:45193062:ACCT:A	donor_gain	0.7400
13:45194719:G:GG	donor_gain	0.7400
13:45199964:GA:G	donor_gain	0.7400
13:45194718:A:AG	donor_gain	0.7100
13:45198780:T:G	acceptor_gain	0.7000
13:45199953:G:GA	donor_gain	0.6800
13:45194560:C:CA	acceptor_gain	0.6700
13:45194760:G:GG	donor_gain	0.6600
13:45197974:C:T	donor_gain	0.6500
13:45194759:A:AG	donor_gain	0.6400
13:45193038:GTG:G	donor_gain	0.6300
13:45193037:AGT:A	donor_gain	0.6200
13:45200408:A:AG	donor_gain	0.6100
13:45194799:G:T	donor_gain	0.6000
13:45194415:C:A	donor_gain	0.5900
13:45193044:CT:C	donor_gain	0.5800
13:45195430:ACTGT:A	donor_gain	0.5600
13:45195469:GGAGA:G	donor_gain	0.5600
13:45193933:T:TA	donor_gain	0.5500
13:45195338:TA:T	acceptor_gain	0.5500
13:45195342:A:G	acceptor_gain	0.5500
13:45193036:AAGT:A	donor_gain	0.5400
13:45195466:ATAGG:A	donor_gain	0.5400
13:45193375:A:C	acceptor_gain	0.5300

AlphaMissense

1711 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:45194091:A:C	C159W	0.999
13:45194287:C:G	R94P	0.999
13:45194299:A:G	L90P	0.999
13:45193900:A:G	L223P	0.998
13:45193916:A:G	C218R	0.998
13:45193945:A:G	L208P	0.998
13:45194056:C:G	R171P	0.998
13:45194092:C:T	C159Y	0.998
13:45194093:A:G	C159R	0.998
13:45194228:C:G	A114P	0.998
13:45194290:A:G	L93P	0.998
13:45194311:A:G	F86S	0.998
13:45194320:C:T	G83D	0.998
13:45194323:T:A	D82V	0.998
13:45194326:C:A	R81M	0.998
13:45194438:A:C	Y44D	0.998
13:45194449:C:A	G40V	0.998
13:45193798:A:G	F257S	0.997
13:45193804:A:G	L255P	0.997
13:45193876:G:T	A231D	0.997
13:45193889:C:G	A227P	0.997
13:45193914:A:C	C218W	0.997
13:45193920:A:C	F216L	0.997
13:45193920:A:T	F216L	0.997
13:45193922:A:G	F216L	0.997
13:45193939:A:G	L210P	0.997
13:45193981:A:G	F196S	0.997
13:45194239:A:G	L110P	0.997
13:45194324:C:G	D82H	0.997
13:45194452:A:T	V39D	0.997

dbSNP variants (sampled 300 via entrez): RS1000462647 (13:45199469 T>C), RS1001075032 (13:45192399 G>C), RS1001378215 (13:45199502 A>C), RS1001403268 (13:45200379 T>C), RS1001434546 (13:45200176 G>A), RS1002047937 (13:45198927 A>G), RS1002503118 (13:45202663 G>A), RS1002601325 (13:45202923 A>G), RS1002637628 (13:45193686 G>A,C), RS1003092459 (13:45196034 A>G,T), RS1003677370 (13:45195166 A>G), RS1003748215 (13:45201769 G>A), RS1003780867 (13:45201553 A>G), RS1004022988 (13:45198406 C>A), RS1004121315 (13:45198845 G>T)

Disease associations

OMIM: gene MIM:620638 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
Nickel	decreases expression	2
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation	1
Silicon Dioxide	affects expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	increases expression	1
Asbestos, Crocidolite	affects methylation	1
Lactic Acid	decreases expression	1
Magnetite Nanoparticles	increases expression	1

Clinical trials (associated diseases)

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