Dyskinesia with orofacial involvement, autosomal recessive

Summary

Dyskinesia with orofacial involvement, autosomal recessive (MONDO:0030625) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyskinesia with orofacial involvement, autosomal recessive
Mondo ID	MONDO:0030625
OMIM	619647
UMLS	C5562036
MedGen	1794246
Is cancer (heuristic)	no

Also known as: DSKOR · dyskinesia with orofacial involvement, autosomal recessive

Data availability: 35 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › dyskinesia with orofacial involvement › dyskinesia with orofacial involvement, autosomal recessive

Related subtypes (1): dyskinesia with orofacial involvement, autosomal dominant

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

35 retrieved; paginated sample, class counts are floors:

16 benign/likely benign, 11 benign, 3 conflicting classifications of pathogenicity, 2 uncertain significance, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
521035	NM_183357.3(ADCY5):c.3037C>T (p.Arg1013Cys)	ADCY5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521036	NM_183357.3(ADCY5):c.409_428del (p.Gly137fs)	ADCY5	Pathogenic	criteria provided, single submitter
1327482	NM_183357.3(ADCY5):c.1762G>A (p.Asp588Asn)	ADCY5	Likely pathogenic	criteria provided, single submitter
1031781	NM_183357.3(ADCY5):c.400G>A (p.Gly134Ser)	ADCY5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1165864	NM_183357.3(ADCY5):c.242C>T (p.Pro81Leu)	ADCY5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1624738	NM_183357.3(ADCY5):c.1127_1129del (p.Leu376_Lys377delinsGln)	ADCY5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2576815	NM_183357.3(ADCY5):c.19G>T (p.Val7Leu)	ADCY5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3588353	NM_183357.3(ADCY5):c.1031C>T (p.Pro344Leu)	ADCY5	Uncertain significance	criteria provided, single submitter
1164245	NM_183357.3(ADCY5):c.1805+13T>C	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1165394	NM_183357.3(ADCY5):c.3064-18G>A	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1167871	NM_183357.3(ADCY5):c.2111+12G>A	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1167872	NM_183357.3(ADCY5):c.753C>T (p.Leu251=)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1169341	NM_183357.3(ADCY5):c.2900+4T>C	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1170029	NM_183357.3(ADCY5):c.29C>T (p.Pro10Leu)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1188957	NM_183357.3(ADCY5):c.3063+54G>A	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1211556	NM_183357.3(ADCY5):c.351G>A (p.Arg117=)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1224969	NM_183357.3(ADCY5):c.2111+100T>C	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1235758	NM_183357.3(ADCY5):c.2257-79T>C	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1236068	NM_183357.3(ADCY5):c.3063+27G>A	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1247103	NM_183357.3(ADCY5):c.1646+58G>A	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1266083	NM_183357.3(ADCY5):c.3064-53C>T	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1274311	NM_183357.3(ADCY5):c.1839C>T (p.Tyr613=)	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1287850	NM_183357.3(ADCY5):c.1646+29C>A	ADCY5	Benign	criteria provided, multiple submitters, no conflicts
1304235	NM_183357.3(ADCY5):c.3532+20G>T	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
697428	NM_183357.3(ADCY5):c.2481C>A (p.Ile827=)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
697629	NM_183357.3(ADCY5):c.1285-6C>T	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
701916	NM_183357.3(ADCY5):c.3015C>A (p.Ala1005=)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
702084	NM_183357.3(ADCY5):c.130C>T (p.His44Tyr)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
702629	NM_183357.3(ADCY5):c.963G>A (p.Gln321=)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
702999	NM_183357.3(ADCY5):c.3696G>A (p.Thr1232=)	ADCY5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADCY5	Orphanet:1429	Benign hereditary chorea
ADCY5	Orphanet:324588	Familial dyskinesia and facial myokymia

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
ADCY5	HGNC:236	ENSG00000173175	O95622	Adenylate cyclase type 5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADCY5	Adenylate cyclase type 5	Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADCY5	Enzyme (other)	yes	4.6.1.1	A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS

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
apex of heart	1
lower esophagus	1
lower esophagus muscularis layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADCY5	193	broad	marker	apex of heart, lower esophagus muscularis layer, lower esophagus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADCY5	1,992

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADCY5	O95622	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. 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
Adenylate cyclase activating pathway	1	1142.0×	0.007	ADCY5
Adenylate cyclase inhibitory pathway	1	761.3×	0.007	ADCY5
PKA activation in glucagon signalling	1	671.8×	0.007	ADCY5
PKA activation	1	634.4×	0.007	ADCY5
Activation of GABAB receptors	1	601.0×	0.007	ADCY5
PKA-mediated phosphorylation of CREB	1	571.0×	0.007	ADCY5
GABA B receptor activation	1	543.8×	0.007	ADCY5
Adrenaline,noradrenaline inhibits insulin secretion	1	393.8×	0.007	ADCY5
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.007	ADCY5
Leishmania parasite growth and survival	1	393.8×	0.007	ADCY5
Calmodulin induced events	1	380.7×	0.007	ADCY5
CaM pathway	1	380.7×	0.007	ADCY5
Ca-dependent events	1	368.4×	0.007	ADCY5
Aquaporin-mediated transport	1	368.4×	0.007	ADCY5
Glucagon signaling in metabolic regulation	1	346.1×	0.007	ADCY5
G-protein mediated events	1	326.3×	0.007	ADCY5
DAG and IP3 signaling	1	317.2×	0.007	ADCY5
GABA receptor activation	1	317.2×	0.007	ADCY5
Response of endothelial cells to shear stress	1	300.5×	0.007	ADCY5
FCGR3A-mediated IL10 synthesis	1	292.8×	0.007	ADCY5
Opioid Signalling	1	265.6×	0.007	ADCY5
PLC beta mediated events	1	265.6×	0.007	ADCY5
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.007	ADCY5
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.007	ADCY5
Cellular responses to mechanical stimuli	1	259.6×	0.007	ADCY5
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.007	ADCY5
GPER1 signaling	1	248.3×	0.007	ADCY5
G alpha (z) signalling events	1	233.1×	0.008	ADCY5
Regulation of insulin secretion	1	219.6×	0.008	ADCY5
Signaling by Hedgehog	1	184.2×	0.009	ADCY5

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
adenylate cyclase-inhibiting dopamine receptor signaling pathway	1	3370.4×	0.002	ADCY5
G protein-coupled adenosine receptor signaling pathway	1	2407.4×	0.002	ADCY5
adenylate cyclase-activating dopamine receptor signaling pathway	1	1532.0×	0.002	ADCY5
cAMP biosynthetic process	1	1404.3×	0.002	ADCY5
cellular response to forskolin	1	1123.5×	0.002	ADCY5
regulation of insulin secretion involved in cellular response to glucose stimulus	1	936.2×	0.002	ADCY5
cellular response to glucagon stimulus	1	842.6×	0.002	ADCY5
vascular endothelial cell response to laminar fluid shear stress	1	732.7×	0.002	ADCY5
renal water homeostasis	1	510.7×	0.003	ADCY5
neuromuscular process controlling balance	1	330.4×	0.004	ADCY5
locomotory behavior	1	179.3×	0.007	ADCY5
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.010	ADCY5
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.010	ADCY5
intracellular signal transduction	1	38.1×	0.026	ADCY5

Therapeutics

Drug target analysis

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

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
ADCY5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ADCY5	43	Binding:33, Functional:9, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADCY5	4.6.1.1	adenylate cyclase

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

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	1	ADCY5
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADCY5	43	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.