DYNC1H1

Chr 14AD

dynein cytoplasmic 1 heavy chain 1

Also known as: CDCBM13, CMT2O, DHC1, DHC1a, DNCH1, DNCL, DNECL, DYHC

NCBI Gene: 1778ENSG00000197102UniProt: Q14204

Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains.This gene encodes a member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, axonal, type 2OMIM #614228
AD
Cortical dysplasia, complex, with other brain malformations 13MIM #614563
AD
Spinal muscular atrophy, lower extremity-predominant 1, ADMIM #158600
AD
5666
ClinVar variants
18
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— DYNC1H1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 223 VUS of 5666 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.08LOEUF
pLI 1.000
Z-score 13.32
OE 0.05 (0.03–0.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
10.97Z-score
OE missense 0.39 (0.37–0.41)
1022 obs / 2593.9 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.03–0.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.39 (0.37–0.41)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 11 / 228.0Missense obs/exp: 1022 / 2593.9Syn Z: -1.72

ClinVar Variant Classifications

5666 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic15
VUS223
Likely Benign194
Benign2
Conflicting4
3
Pathogenic
15
Likely Pathogenic
223
VUS
194
Likely Benign
2
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
2
12
1
0
15
VUS
9
194
18
2
223
Likely Benign
0
17
71
106
194
Benign
0
0
2
0
2
Conflicting
—4
Total1122395108441

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DYNC1H1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DYNC1H1-related severe intellectual disability with neuronal migration disorder

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

DYNC1H1-related spinal muscular atrophy, lower extremity-predominant

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, axonal, type 2O

MIM #614228

Molecular basis of disorder known

Autosomal dominant

Cortical dysplasia, complex, with other brain malformations 13

MIM #614563

Molecular basis of disorder known

Autosomal dominant

Spinal muscular atrophy, lower extremity-predominant 1, AD

MIM #158600

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The expanding clinical and genetic spectrum of DYNC1H1-related disorders.
Möller B et al.·Brain
2025
Clinical features and genotype-phenotype correlations in epilepsy patients with de novo DYNC1H1 variants.
Cuccurullo C et al.·Epilepsia
2024Cohort
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
DYNC1H1-related epilepsy: Genotype-phenotype correlation.
Liu W et al.·Dev Med Child Neurol
2023
A novel variant in DYNC1H1 could contribute to human amyotrophic lateral sclerosis-frontotemporal dementia spectrum.
Mentis AA et al.·Cold Spring Harb Mol Case Stud
2022Review
Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits.
Ramos RL et al.·Neurobiol Dis
2024
Anatomo-Electro-Clinical Phenotypes in Children With Epilepsy and DYNC1H1 Mutations.
Gutiérrez-Delicado E et al.·Pediatr Neurol
2025
The clinical-phenotype continuum in DYNC1H1-related disorders-genomic profiling and proposal for a novel classification.
Becker LL et al.·J Hum Genet
2020
Neurogenic arthrogryposis and the power of phenotyping.
Rossor AM et al.·Neuromuscul Disord
2021Review
DYNC1H1 in Spinal Muscular Atrophy: Diagnostic Findings From Two Families and a Comprehensive Review of Its Role in Neuromuscular and Neurodevelopmental Disorders.
Namdari M et al.·Mol Genet Genomic Med
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools