DYNC1H1: Cytoplasmic Dynein Heavy Chain 1
A key motor protein in retrograde axonal transport, associated with neurodevelopmental and neurodegenerative disorders.
Gene Information Card
| Symbol | DYNC1H1 |
|---|---|
| Full Name | dynein cytoplasmic 1 heavy chain 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q32.31 |
| NCBI Gene ID | 1778 ncbi.nlm.nih.gov/gene/1778 |
| Ensembl ID | ENSG00000197102 |
| UniProt ID | Q14204 |
| OMIM ID | 600112 |
| HGNC ID | 2961 |
| Aliases | DHC1, DHC1a, DNCH1, DNCL, DYHC, Dnchc1, p22 |
Description
The DYNC1H1 gene encodes the heavy chain subunit of cytoplasmic dynein 1, a large multi-subunit motor complex that drives retrograde transport along microtubules toward the minus end. This protein is essential for axonal transport, cell division, and intracellular trafficking. Mutations in DYNC1H1 are associated with a spectrum of neurological disorders, including Charcot-Marie-Tooth disease type 2O (CMT2O), spinal muscular atrophy with lower extremity predominance (SMA-LED), and malformations of cortical development (MCD).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2O (CMT2O) | Dominant-negative or loss-of-function mutations impair retrograde axonal transport in peripheral neurons, leading to axonal degeneration. | ClinVar, OMIM #614228 |
| Spinal muscular atrophy with lower extremity predominance (SMA-LED) | Missense mutations in the motor domain disrupt dynein function, causing selective motor neuron vulnerability. | ClinVar, OMIM #158600 |
| Malformations of cortical development (MCD) | De novo mutations impair neuronal migration during corticogenesis, resulting in pachygyria or polymicrogyria. | ClinVar, OMIM #600112 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.9 | Medium |
| Lung | 6.2 | Medium |
| Heart | 5.8 | Medium |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.3 | High expression; used in neuronal transport studies |
| HeLa (cervical carcinoma) | 9.7 | Moderate expression; mitotic dynein function |
| HEK293 (embryonic kidney) | 8.1 | Moderate expression; common overexpression model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1792G>A (p.Glu598Lys) | Missense | Rare | Dominant-negative; impairs ATPase activity; associated with SMA-LED |
| c.1073T>C (p.Ile358Thr) | Missense | Rare | Gain-of-function?; linked to CMT2O |
| c.601C>T (p.Arg201Cys) | Missense | De novo | Loss-of-function; causes MCD |
Mutation functional classification
Loss of Function (LOF)
Truncating or missense mutations in the tail domain reduce dynein complex assembly and cargo binding, leading to impaired retrograde transport.
Gain of Function (GOF)
Some missense mutations in the motor domain (e.g., p.Ile358Thr) may increase ATPase activity or alter microtubule binding, though evidence is limited.
Dominant Negative (DN)
Mutations in the AAA+ ATPase domain (e.g., p.Glu598Lys) produce defective motor subunits that poison the dynein complex, causing dominant inheritance.
View complete mutation data：
Gene Ontology (GO)
| • microtubule motor activity | • ATP binding |
| • retrograde axonal transport | • cell division |
| • centrosome localization |
Pathways
• Axonal transport (KEGG: hsa04728)
• Dynein-mediated cargo transport (Reactome: R-HSA-983189)
Protein Summary
DYNC1H1 is a ~532 kDa protein that forms the core of the cytoplasmic dynein 1 complex. It contains an N-terminal tail domain for cargo binding and dimerization, and a C-terminal motor domain with six AAA+ ATPase modules that generate force along microtubules. The protein is ubiquitously expressed but enriched in neurons, where it is critical for retrograde transport of vesicles, organelles, and signaling molecules.
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