Dystonia 34, myoclonic

Summary

Dystonia 34, myoclonic (MONDO:0030538) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dystonia 34, myoclonic
Mondo ID	MONDO:0030538
OMIM	619724
DOID	DOID:0060957
UMLS	C5676907
MedGen	1805016
GARD	0025599
Is cancer (heuristic)	no

Also known as: DYT34

Data availability: 10 ClinVar variants.

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 › dystonia 34, myoclonic

Related subtypes (23): lymphatic malformation 5, Woodhouse-Sakati syndrome, severe motor and intellectual disabilities-sensorineural deafness-dystonia syndrome, torsion dystonia 7, developmental malformations-deafness-dystonia syndrome, dopa-responsive dystonia due to sepiapterin reductase deficiency, ataxia - oculomotor apraxia type 4, striatonigral degeneration, childhood-onset, dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, dystonia 28, childhood-onset, isolated dystonia, combined dystonia, dystonia 30, dystonia 31, dystonia 32, dystonia 33, dystonia 35, childhood-onset, familial idiopathic torsion dystonia, dystonia, focal, task-specific, dystonia 37, early-onset, with striatal lesions, dystonia 22, juvenile-onset, dystonia 22, adult-onset, autosomal dominant dopa-responsive dystonia

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

10 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3069186	NM_021614.4(KCNN2):c.1384dup (p.Thr462fs)	KCNN2	Pathogenic	criteria provided, single submitter
4814029	NM_021614.4(KCNN2):c.1780-2A>G	KCNN2	Likely pathogenic	no assertion criteria provided
2631563	NM_021614.4(KCNN2):c.2344A>G (p.Thr782Ala)	KCNN2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1338743	NM_021614.4(KCNN2):c.1748G>A (p.Gly583Glu)	KCNN2	Uncertain significance	criteria provided, single submitter
2506500	NM_021614.4(KCNN2):c.428_439dup (p.Gln146_Ser147insTyrAlaGlnGln)	KCNN2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3234849	NM_021614.4(KCNN2):c.428A>C (p.Tyr143Ser)	KCNN2	Uncertain significance	criteria provided, single submitter
3251996	NM_021614.4(KCNN2):c.800_801insTGC (p.Ala270_Val271insAla)	KCNN2	Uncertain significance	criteria provided, single submitter
3362336	NM_021614.4(KCNN2):c.547T>C (p.Ser183Pro)	KCNN2	Uncertain significance	criteria provided, single submitter
3591578	NM_021614.4(KCNN2):c.2294A>G (p.Tyr765Cys)	KCNN2	Uncertain significance	criteria provided, single submitter
4277812	NM_021614.4(KCNN2):c.809_811dup (p.Ala270_Val271insAla)	KCNN2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KCNN2	HGNC:6291	ENSG00000080709	Q9H2S1	Small conductance calcium-activated potassium channel protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNN2	Small conductance calcium-activated potassium channel protein 2	Small conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calci…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNN2	Ion channel	yes		CaM-bd_dom, K_chnl_dom, K_chnl_Ca-activ_SK

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
right adrenal gland	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNN2	213	broad	marker	secondary oocyte, oocyte, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNN2	1,048

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KCNN2	Q9H2S1	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Acetylcholine inhibits contraction of outer hair cells	1	2284.0×	0.003	KCNN2
Ca2+ activated K+ channels	1	1142.0×	0.003	KCNN2
Sensory processing of sound	1	308.6×	0.008	KCNN2
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.009	KCNN2
Potassium Channels	1	134.3×	0.010	KCNN2
Sensory Perception	1	95.2×	0.012	KCNN2
Neuronal System	1	44.3×	0.023	KCNN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
membrane repolarization during atrial cardiac muscle cell action potential	1	2808.7×	0.001	KCNN2
regulation of potassium ion transmembrane transport	1	624.1×	0.003	KCNN2
potassium ion transport	1	191.5×	0.007	KCNN2
potassium ion transmembrane transport	1	135.9×	0.007	KCNN2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KCNN2	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CEPHARANTHINE	2	KCNN2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
KCNN2	22	Binding:22

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
CEPHARANTHINE	2	KCNN2

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	1	KCNN2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.