KCTD17

protein-coding

potassium channel tetramerization domain containing 17, the group of KCTD family

Gene summary

This gene encodes a protein that belongs to a conserved family of potassium channel tetramerization domain (KCTD)-containing proteins. The encoded protein functions in ciliogenesis by acting as a substrate adaptor for the cullin3-based ubiquitin-conjugating enzyme E3 ligase, and targets trichoplein, a keratin-binding protein, for degradation via polyubiquitinylation. A mutation in this gene is associated with autosomal dominant myoclonic dystonia 26. [provided by RefSeq, Nov 2016]

MANE transcript

NM_001282684.2

Inheritance

ClinVar variants

P:4U:82B:47

Top phenotype

Dystonia 26, myoclonic

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr22:37,051,739-37,063,390

External References & Databases

Ensembl (ENSG00000100379)

Transcript & Mutation Effects

hg38 • Region Span ~11.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myoclonic dystonia 26STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014620

Submitter: Labcorp Genetics (formerly Invitae)

myoclonic dystonia 26STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014620

Submitter: PanelApp Australia

myoclonus-dystonia syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000903

Submitter: Orphanet

myoclonic dystonia 26LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014620

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Dystonia 26, myoclonicAD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Surgery with pallidal deep brain stimulation has been described as beneficial, though the impact of early diagnosis is unclear

Refs: 25983243

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCTD17 variants in ClinVar

5 Conditions Cataloged

Myoclonic dystonia 26Total: 131

Inborn genetic diseasesTotal: 38

not providedTotal: 31

not specifiedTotal: 12

KCTD17-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001282684.2. 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			1 clinvar	37 clinvar	2 clinvar	40
missense	1 clinvar	1 clinvar	74 clinvar	8 clinvar		84
nonsense			2 clinvar			2
start loss			2 clinvar			2
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	2	2	82	45	2	133

Loading ClinVar variants...

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_001282684.2	RefSeq	NP_001269613.2	9	MANE Select
ENST00000403888.8	Ensembl	ENSP00000385096.4	9	MANE Select
NM_001282685.2	RefSeq	NP_001269614.2	6	Standard
NM_001282686.2	RefSeq	NP_001269615.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell projection organization
endoplasmic reticulum calcium ion homeostasis
proteasome-mediated ubiquitin-dependent protein catabolic process
positive regulation of cilium assembly
protein homooligomerization

Molecular Function

protein binding
identical protein binding
cullin family protein binding

Cellular Component

cytoplasm
endoplasmic reticulum
Cul3-RING ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000402077
Coding exons: 8
Length: 11652
Individuals with no LoFs: 125538
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125545
p: 0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.58	99	154	0.642	0.00000948	1899
Missense (PolyPhen)		16	44.618	0.3586		459
Synonymous	-0.133	62	60.7	1.02	0.00000384	555
Loss of Function	2.04	5	12.9	0.387	5.50e-7	176

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Is a positive regulator of ciliogenesis, playing a crucial role in the initial steps of axoneme extension. It acts as a substrate-adapter for CUL3-RING ubiquitin ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of TCHP, a protein involved in ciliogenesis down-regulation (PubMed:25270598). May be involved in endoplasmic reticulum calcium ion homeostasis (PubMed:25983243). {ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:25983243}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.460
RVIS EVS: 0.08
RVIS percentile EVS: 60.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.800

Gene Damage Prediction

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