Myoclonic dystonia 26

Summary

Myoclonic dystonia 26 (MONDO:0014620) is a disease caused by KCTD17 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: KCTD17 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 141

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myoclonic dystonia 26
Mondo ID	MONDO:0014620
OMIM	616398
DOID	DOID:0090036
UMLS	C4225341
MedGen	904244
GARD	0016103
Is cancer (heuristic)	no

Also known as: dystonia 26, myoclonic · DYT26 · KCTD17 myoclonus-dystonia syndrome · myoclonic dystonia type 26 · myoclonus-dystonia syndrome caused by mutation in KCTD17

Data availability: 141 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › inherited dystonia › combined dystonia › myoclonus-dystonia syndrome › myoclonic dystonia 26

Related subtypes (2): myoclonic dystonia 11, myoclonic dystonia 15

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

141 retrieved; paginated sample, class counts are floors:

66 likely benign, 55 uncertain significance, 8 benign, 5 conflicting classifications of pathogenicity, 3 pathogenic, 2 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
191372	NM_001282684.2(KCTD17):c.413G>A (p.Arg138His)	KCTD17	Pathogenic	criteria provided, multiple submitters, no conflicts
2765450	NM_001282684.2(KCTD17):c.547dup (p.Val183fs)	KCTD17	Pathogenic	criteria provided, single submitter
3237472	NM_001282684.2(KCTD17):c.487-1G>C	KCTD17	Pathogenic	criteria provided, single submitter
3909974	NM_001282684.2(KCTD17):c.487-1G>T	KCTD17	Likely pathogenic	criteria provided, single submitter
4813647	NM_001282684.2(KCTD17):c.461T>A (p.Met154Lys)	KCTD17	Likely pathogenic	no assertion criteria provided
2424101	NC_000022.10:g.(?37154355)(39148633_?)del	ANKRD54	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1924264	NM_001282684.2(KCTD17):c.580G>A (p.Gly194Arg)	KCTD17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2061604	NM_001282684.2(KCTD17):c.601C>T (p.Arg201Cys)	KCTD17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2279970	NM_001282684.2(KCTD17):c.331G>A (p.Gly111Ser)	KCTD17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
571150	NM_001282684.2(KCTD17):c.853C>T (p.Arg285Cys)	KCTD17	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027881	NM_001282684.2(KCTD17):c.5G>C (p.Arg2Thr)	KCTD17	Uncertain significance	criteria provided, single submitter
1364106	NM_001282684.2(KCTD17):c.20A>G (p.Glu7Gly)	KCTD17	Uncertain significance	criteria provided, single submitter
1365211	NM_001282684.2(KCTD17):c.668T>C (p.Val223Ala)	KCTD17	Uncertain significance	criteria provided, single submitter
1433864	NM_001282684.2(KCTD17):c.854G>A (p.Arg285His)	KCTD17	Uncertain significance	criteria provided, multiple submitters, no conflicts
1444805	NM_001282684.2(KCTD17):c.571A>G (p.Thr191Ala)	KCTD17	Uncertain significance	criteria provided, single submitter
1473076	NM_001282684.2(KCTD17):c.17G>A (p.Gly6Glu)	KCTD17	Uncertain significance	criteria provided, single submitter
1512543	NM_001282684.2(KCTD17):c.856C>G (p.Pro286Ala)	KCTD17	Uncertain significance	criteria provided, single submitter
1516101	NM_001282684.2(KCTD17):c.332G>A (p.Gly111Asp)	KCTD17	Uncertain significance	criteria provided, single submitter
1721924	NM_001282684.2(KCTD17):c.332G>T (p.Gly111Val)	KCTD17	Uncertain significance	criteria provided, single submitter
1974785	NM_001282684.2(KCTD17):c.436G>A (p.Glu146Lys)	KCTD17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2037840	NM_001282684.2(KCTD17):c.617C>T (p.Thr206Met)	KCTD17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2041567	NM_001282684.2(KCTD17):c.380C>T (p.Thr127Met)	KCTD17	Uncertain significance	criteria provided, single submitter
2051515	NM_001282684.2(KCTD17):c.656AGGTGGAGG[1] (p.219EVE[1])	KCTD17	Uncertain significance	criteria provided, single submitter
2060770	NM_001282684.2(KCTD17):c.790C>T (p.Arg264Cys)	KCTD17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2062678	NM_001282684.2(KCTD17):c.346A>C (p.Ile116Leu)	KCTD17	Uncertain significance	criteria provided, single submitter
2068942	NM_001282684.2(KCTD17):c.475C>T (p.Arg159Cys)	KCTD17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2071637	NM_001282684.2(KCTD17):c.283G>C (p.Asp95His)	KCTD17	Uncertain significance	criteria provided, single submitter
2107504	NM_001282684.2(KCTD17):c.770C>T (p.Pro257Leu)	KCTD17	Uncertain significance	criteria provided, single submitter
2151438	NM_001282684.2(KCTD17):c.892G>A (p.Ala298Thr)	KCTD17	Uncertain significance	criteria provided, multiple submitters, no conflicts
2164685	NM_001282684.2(KCTD17):c.202G>A (p.Ala68Thr)	KCTD17	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
KCTD17	Strong	Autosomal dominant	myoclonic dystonia 26	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCTD17	Orphanet:36899	Myoclonus-dystonia syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCTD17	HGNC:25705	ENSG00000100379	Q8N5Z5	BTB/POZ domain-containing protein KCTD17	gencc,clinvar
ANKRD54	HGNC:25185	ENSG00000100124	Q6NXT1	Ankyrin repeat domain-containing protein 54	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCTD17	BTB/POZ domain-containing protein KCTD17	Substrate-adapter for CUL3-RING ubiquitin ligase complexes which mediates the ubiquitination and subsequent proteasomal degradation of TCHP, a protein involved in ciliogenesis down-regulation.
ANKRD54	Ankyrin repeat domain-containing protein 54	Plays an important role in regulating intracellular signaling events associated with erythroid terminal differentiation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCTD17	Other/Unknown	no		BTB/POZ_dom, T1-type_BTB, SKP1/BTB/POZ_sf
ANKRD54	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caudate nucleus	1
nucleus accumbens	1
putamen	1
kidney epithelium	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCTD17	225	ubiquitous	yes	putamen, caudate nucleus, nucleus accumbens
ANKRD54	247	ubiquitous	marker	right uterine tube, kidney epithelium, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCTD17	1,130
ANKRD54	1,122

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCTD17	Q8N5Z5	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKRD54	Q6NXT1	68.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of intracellular signal transduction	1	443.5×	0.007	ANKRD54
endoplasmic reticulum calcium ion homeostasis	1	421.3×	0.007	KCTD17
positive regulation of cilium assembly	1	383.0×	0.007	KCTD17
positive regulation of erythrocyte differentiation	1	255.3×	0.007	ANKRD54
nucleocytoplasmic transport	1	195.9×	0.007	ANKRD54
cell projection organization	1	187.2×	0.007	KCTD17
protein homooligomerization	1	61.1×	0.019	KCTD17
proteasome-mediated ubiquitin-dependent protein catabolic process	1	26.1×	0.038	KCTD17

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCTD17	0	0
ANKRD54	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ANKRD54	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	KCTD17, ANKRD54

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
KCTD17	0	—
ANKRD54	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.