Dyneinopathy

Summary

Dyneinopathy (MONDO:1040031) is a disease caused by DYNC1H1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DYNC1H1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyneinopathy
Mondo ID	MONDO:1040031
GARD	0027115
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › syndromic intellectual disability › dyneinopathy

Related subtypes (16): Smith-Magenis syndrome, intellectual disability, Buenos-Aires type, intellectual disability, Wolff type, CK syndrome, AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome, 7p22.1 microduplication syndrome, 9p13 microdeletion syndrome, 3q27.3 microdeletion syndrome, 9q31.1q31.3 microdeletion syndrome, Rubinstein-Taybi syndrome, X-linked syndromic intellectual disability, 9q33.3q34.11 microdeletion syndrome, autosomal recessive syndromic intellectual disability, autosomal dominant syndromic intellectual disability, aplasia cutis-enamel dysplasia syndrome, 2p25.3 microduplication syndrome

Subtypes (2): Charcot-Marie-Tooth disease axonal type 2O, intellectual disability, autosomal dominant 13

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
374099	NM_001376.5(DYNC1H1):c.751C>T (p.Arg251Cys)	DYNC1H1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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
DYNC1H1	Strong	Autosomal dominant	dyneinopathy	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DYNC1H1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
DYNC1H1	Orphanet:209341	DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
DYNC1H1	Orphanet:284232	Autosomal dominant Charcot-Marie-Tooth disease type 2O

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
DYNC1H1	HGNC:2961	ENSG00000197102	Q14204	Cytoplasmic dynein 1 heavy chain 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYNC1H1	Cytoplasmic dynein 1 heavy chain 1	Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYNC1H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail

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
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYNC1H1	290	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DYNC1H1	4,215

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYNC1H1	Q14204	97

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. 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
Aggrephagy	1	248.3×	0.015	DYNC1H1
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.015	DYNC1H1
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	193.6×	0.015	DYNC1H1
Loss of Nlp from mitotic centrosomes	1	158.6×	0.015	DYNC1H1
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.015	DYNC1H1
AURKA Activation by TPX2	1	152.3×	0.015	DYNC1H1
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.015	DYNC1H1
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.015	DYNC1H1
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.015	DYNC1H1
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.015	DYNC1H1
Anchoring of the basal body to the plasma membrane	1	113.1×	0.015	DYNC1H1
COPI-mediated anterograde transport	1	109.8×	0.015	DYNC1H1
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.015	DYNC1H1
MHC class II antigen presentation	1	89.2×	0.015	DYNC1H1
Resolution of Sister Chromatid Cohesion	1	86.5×	0.015	DYNC1H1
HCMV Early Events	1	81.0×	0.015	DYNC1H1
RHO GTPases Activate Formins	1	77.7×	0.015	DYNC1H1
Mitotic Prometaphase	1	69.2×	0.016	DYNC1H1
Separation of Sister Chromatids	1	60.7×	0.017	DYNC1H1
Neutrophil degranulation	1	23.1×	0.043	DYNC1H1

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
regulation of metaphase plate congression	1	3370.4×	0.002	DYNC1H1
establishment of spindle localization	1	2808.7×	0.002	DYNC1H1
positive regulation of spindle assembly	1	2106.5×	0.002	DYNC1H1
positive regulation of intracellular transport	1	1685.2×	0.002	DYNC1H1
retrograde axonal transport	1	1532.0×	0.002	DYNC1H1
P-body assembly	1	1053.2×	0.002	DYNC1H1
regulation of mitotic spindle organization	1	842.6×	0.002	DYNC1H1
nuclear migration	1	732.7×	0.002	DYNC1H1
stress granule assembly	1	601.9×	0.002	DYNC1H1
cytoplasmic microtubule organization	1	343.9×	0.004	DYNC1H1
mitotic spindle organization	1	271.8×	0.004	DYNC1H1
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	DYNC1H1
cell division	1	46.2×	0.022	DYNC1H1

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
DYNC1H1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	DYNC1H1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DYNC1H1	7	Binding:7

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)
MOLIBRESIB	2	DYNC1H1

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	DYNC1H1
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.