KCTD6

protein-coding

potassium channel tetramerization domain containing 6, the group of KCTD family

Gene summary

Enables ankyrin binding activity; cullin family protein binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001128214.2

Inheritance

—

ClinVar variants

U:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr3:58,492,096-58,502,360

External References & Databases

Ensembl (ENSG00000168301)

Transcript & Mutation Effects

hg38 • Region Span ~10.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCTD6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001128214.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			12 clinvar			12
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	12	0	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001128214.2	RefSeq	NP_001121686.1	2	MANE Select
ENST00000404589.8	Ensembl	ENSP00000384948.3	2	MANE Select
NM_153331.3	RefSeq	NP_699162.3	2	Standard
ENST00000355076.6	Ensembl	ENSP00000347188.6	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transcriptional regulation by RUNX1
Signal Transduction
Gene expression (Transcription)
Generic Transcription Pathway
Post-translational protein modification

Biological Process

ubiquitin-dependent protein catabolic process
protein ubiquitination
regulation of intracellular estrogen receptor signaling pathway
regulation of growth
post-translational protein modification

Molecular Function

protein binding
ankyrin binding
identical protein binding
cullin family protein binding

Cellular Component

cytosol
M band

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355076
Coding exons: 2
Length: 10247
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125743
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.13	61	129	0.473	0.00000722	1563
Missense (PolyPhen)		9	34.043	0.26437		389
Synonymous	0.757	41	47.6	0.861	0.00000256	463
Loss of Function	1.45	4	8.57	0.467	5.79e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable substrate-specific adapter of a BCR (BTB-CUL3- RBX1) E3 ubiquitin-protein ligase complex mediating the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes the ubiquitination of HDAC1; the function seems to depend on KCTD11:KCTD6 oligomerization. Can function as antagonist of the Hedgehog pathway by affecting the nuclear transfer of transcription factor GLI1; the function probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. Inhibits cell growth and tumorigenicity of medulloblastoma (MDB) (PubMed:21472142). Involved in regulating protein levels of ANK1 isoform Mu17 probably implicating CUL3- dependent proteasomal degradation (PubMed:22573887). {ECO:0000269|PubMed:21472142, ECO:0000269|PubMed:22573887}.;

Recessive Scores

pRec: 0.0993

Intolerance Scores

LoFtool: 0.300
RVIS EVS: -0.05
RVIS percentile EVS: 49.39

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low