DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1

Migration, Crosslink

📖

DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1

active

wiki page Created: 2026-04-02T07:19:18 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-genes-dync2h1

📖 Wiki Page

gene1646 wordssynced 2026-04-02

DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>DYNC2H1</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Dynein Cytoplasmic 2 Heavy Chain 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q22.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1771</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q8IVD4</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000130938</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>DYH1, HL12, DYHC2, DNCH2, DHC2</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Function</td>
</tr>
<tr>
<td class="label">DYNC2I1</td>
<td>Intermediate chain - cargo binding</td>
</tr>
<tr>
<td class="label">DYNC2I2</td>
<td>Alternative intermediate chain</td>
</tr>
<tr>
<td class="label">DYNC2LI1</td>
<td>Light intermediate chain</td>
</tr>
<tr>
<td class="label">DYNC2LI2</td>
<td>Alternative light intermediate chain</td>
</tr>
<tr>
<td class="label">DYNC1L1</td>
<td>Cytoplasmic dynein 1 - related complex</td>
</tr>
<tr>
<td class="label">DCTN1</td>
<td>Dynactin - complex stabilizer</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges<

...

DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>DYNC2H1</td>
</tr>
<tr>
<td class="label">Name</td>
<td>Dynein Cytoplasmic 2 Heavy Chain 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q22.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>1771</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q8IVD4</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000130938</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein-coding</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>DYH1, HL12, DYHC2, DNCH2, DHC2</td>
</tr>
<tr>
<td class="label">Interactor</td>
<td>Function</td>
</tr>
<tr>
<td class="label">DYNC2I1</td>
<td>Intermediate chain - cargo binding</td>
</tr>
<tr>
<td class="label">DYNC2I2</td>
<td>Alternative intermediate chain</td>
</tr>
<tr>
<td class="label">DYNC2LI1</td>
<td>Light intermediate chain</td>
</tr>
<tr>
<td class="label">DYNC2LI2</td>
<td>Alternative light intermediate chain</td>
</tr>
<tr>
<td class="label">DYNC1L1</td>
<td>Cytoplasmic dynein 1 - related complex</td>
</tr>
<tr>
<td class="label">DCTN1</td>
<td>Dynactin - complex stabilizer</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Introduction

DYNC2H1 (Dynein Cytoplasmic 2 Heavy Chain 1) encodes the heavy chain of cytoplasmic dynein-2, a motor protein complex involved in intracellular transport, retrograde axonal transport, and the function of cilia and flagella. Dyneins are members of the ATPase protein family that move along microtubules toward their minus ends, transporting cargo from the cell periphery toward the cell center. This gene is essential for proper neuronal function and has been implicated in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic Lateral Sclerosis (ALS).

Cytoplasmic dynein-2 (also known as dynein-2) is distinct from cytoplasmic dynein-1, which is the primary motor for retrograde transport in neurons. While dynein-1 is well-studied in neurodegeneration, dynein-2 has unique functions in intracellular trafficking that are relevant to neuronal health and disease.

Gene Function

Core Motor Protein Function

DYNC2H1 encodes the cytoplasmic dynein 2 heavy chain 1, a microtubule motor protein that powers minus-end-directed intracellular transport along microtubule tracks. Dyneins are among the largest and most complex molecular motors, functioning as the primary retrograde transport system in eukaryotic cells. The heavy chain contains the motor domain that hydrolyzes ATP to generate force for cargo movement toward the minus end of microtubules (toward the cell center).

The dynein motor complex consists of multiple subunits:

Heavy chains: Motor activity (DYNC2H1 is the key heavy chain)
Intermediate chains: Cargo binding and regulation
Light chains: Various regulatory functions
Light intermediate chains: Cargo adaptor interactions

Retrograde Axonal Transport

Dynein-mediated transport is fundamental to neuronal health. Neurons have extremely long axons requiring efficient transport systems to move cargo between the cell body and synaptic terminals. DYNC2H1 dysfunction contributes to neurodegeneration through:

Retrograde transport impairment: Reduced transport of signaling endosomes, organelles, and recycling vesicles
Axonal swellings: Accumulation of organelles and transport intermediates
Synaptic dysfunction: Impaired delivery of synaptic proteins and organelles to nerve terminals

Intraflagellar Transport (IFT)

DYNC2H1 plays a critical role in intraflagellar transport (IFT), the process by which protein complexes are transported bidirectionally along the axoneme of cilia and flagella. IFT is essential for:

Cilium assembly: Building and maintaining ciliary structure
Ciliary membrane protein trafficking: Transporting proteins to the ciliary membrane
Signal transduction: Moving signaling components to cilia
Retrograde transport: Carrying cargo from the ciliary tip back to the cell body

The IFT system operates through:

Anterograde transport: IFT-B complex moved by kinesin-2 toward ciliary tip
Retrograde transport: IFT-A complex moved by dynein-2 (DYNC2H1) toward ciliary base

This bidirectional transport is essential for maintaining ciliary homeostasis and function.

Ciliary Function

Cilia are membrane-bound organelles that extend from the cell surface and perform diverse functions:

Sensory cilia: Detect chemical and mechanical signals

Motile cilia: Generate fluid flow

Primary cilia: Coordinate signaling pathways (Shh, Wnt, PDGFRα)

DYNC2H1 localizes to the ciliary tip, axoneme, and ciliary base, participating in both motile and non-motile cilium assembly. The protein is essential for:

Ciliary length control
Ciliary membrane protein composition
Ciliary signaling platform formation

Role in Neurodegeneration

Link to Alzheimer's Disease

In Alzheimer's disease (AD), dynein function is compromised through multiple mechanisms:

Amyloid-β effects: Amyloid-β oligomers can impair dynein function
Tau pathology: Hyperphosphorylated tau disrupts microtubule-based transport
Dysfunction of signaling: Reduced retrograde signaling from synapses to cell bodies

The failure of dynein-mediated transport contributes to:

Synaptic loss
Somal degeneration
Impaired axonal maintenance
Autophagy impairment
Endosomal dysfunction

Link to Parkinson's Disease

Dynein dysfunction is relevant to Parkinson's disease pathogenesis:

Alpha-synuclein transport: Dynein mediates endosomal transport of alpha-synuclein
LRRK2 interactions: LRRK2 mutations may affect dynein function
Mitochondrial trafficking: Dynein transports mitochondria along axons

Dynein impairment exacerbates:

Mitochondrial dysfunction
Protein aggregation
Dopaminergic neuron vulnerability in the substantia nigra

Implications for Amyotrophic Lateral Sclerosis (ALS)

In ALS, dynein mutations have been identified that contribute to motor neuron degeneration:

Dynactin mutations: Stabilize dynein function; mutations cause motor neuron disease
Transport defects: Impaired organelle and protein transport
Axonal degeneration: Reduced retrograde transport of survival signals
TDP-43 pathology: Disrupts transport machinery
Autophagy dysfunction: Impaired clearance of aggregates

Role in Frontotemporal Dementia (FTD)

FTD involves frontotemporal lobe degeneration with transport defects:

Tau pathology: Disrupts microtubule networks used by dynein
TDP-43 inclusions: May impair transport machinery
Cargo accumulation: Accumulation of transport intermediates

Other Neurodegenerative Conditions

DYNC2H1 alterations have been documented in:

Huntington's Disease: Dynein function is impaired, contributing to transport deficits
Charcot-Marie-Tooth Disease: Dynein mutations cause a subtype of this hereditary neuropathy
Prion Diseases: Dynein-mediated transport is disrupted in prion-infected neurons

Expression Pattern

Brain Expression

DYNC2H1 is expressed throughout the brain with high levels in:

Cerebral cortex: High metabolic activity and long axons
Hippocampus: Critical for memory formation
Basal ganglia: Motor control centers
Cerebellum: Motor coordination
Substantia nigra: Dopaminergic neurons
Spinal cord: Motor neurons

Cellular Localization

Within neurons:

Cell body (soma): Primary location of dynein complex assembly
Dendrites: Transport of synaptic proteins
Axons: Long-distance retrograde transport
Growth cones: Guidance during development and regeneration
Synaptic terminals: Retrograde signaling

Non-Neuronal Expression

DYNC2H1 is expressed in various cell types:

Epithelial cells (ciliated)
Fibroblasts (primary cilia)
Neuronal precursors
Glial cells

Protein-Protein Interactions

Core Dynein Complex

IFT Components

IFT-B complex subunits (anterograde coupling)
IFT-A complex subunits (retrograde transport)
IFT74/81 - Tubulin transport
BBSome complex (ciliary trafficking)

Regulatory Proteins

ROCK: Rho-kinase - phosphorylation regulation
Lis1: Dynein regulator (lissencephaly)
Ndel1: Neuronal dynein regulator
BICD2: Dynactin binding protein

Therapeutic Implications

Targeting Axonal Transport

Modulating dynein function offers therapeutic potential:

Enhancing retrograde transport: Improving survival signaling

Restoring cargo delivery: Delivering synaptic proteins

Reducing transport burden: Decreasing aggregate transport

Autophagy enhancement: Improving aggregate clearance

Small Molecule Approaches

Dynein activators: Enhance motor function
Microtubule stabilizers: Improve tracks for transport
ATPase modulators: Enhance energy utilization
Dynactin stabilizers: Improve complex function

Gene Therapy Potential

Viral vector delivery of functional DYNC2H1
RNA-based approaches to restore expression
CRISPR approaches for mutation correction

Mermaid Diagram: Dynein-2 Function in Retrograde Transport

Mermaid diagram (expand to render)

Disease Associations

Short Rib-Polydactyly Syndrome Type 3

DYNC2H1 mutations cause short rib-polydactyly syndrome type 3 (SRPS3), also known as Verma-Naumoff syndrome:

Skeletal dysplasia
Short ribs
Polydactyly
Often fatal in perinatal period

Asphyxiating Thoracic Dysplasia (Jeune Syndrome)

DYNC2H1 is one of several genes causing Jeune syndrome:

Narrow thoracic cage
Short ribs
Respiratory distress
Variable extrathoracic features

Neurodegenerative Diseases

While not a primary cause, DYNC2H1 dysfunction contributes to:

Alzheimer's disease progression
Parkinson's disease pathogenesis
Amyotrophic lateral sclerosis
Frontotemporal dementia
Charcot-Marie-Tooth disease

Research Directions

Key areas of ongoing research include:

Mechanistic Studies: Understanding how DYNC2H1 dysfunction contributes to specific neurodegenerative disease processes

Transport Kinetics: High-resolution studies of dynein movement along microtubules

Cargo Adaptor Identification: Identifying the full repertoire of cargo adaptors

Therapeutic Targeting: Developing small molecules that can modulate dynein function

Axonal Transport Assays: Using live-cell imaging to monitor dynein-mediated transport

iPSC Models: Using patient-derived neurons to study DYNC2H1 function

References

[Roberts et al., 2013 - Cytoplasmic dynein and its subunits](https://pubmed.ncbi.nlm.nih.gov/23589299/)

[Kardon & Vale, 2009 - Dynein as a neuronal transport motor](https://pubmed.ncbi.nlm.nih.gov/19386009/)

[Pazour et al., 2005 - Intraflagellar transport and ciliary assembly](https://pubmed.ncbi.nlm.nih.gov/15897869/)

[Baker et al., 2004 - IFT dynein motor regulation](https://pubmed.ncbi.nlm.nih.gov/15103158/)

[Stokin et al., 2005 - Axonal transport and Alzheimer's disease](https://pubmed.ncbi.nlm.nih.gov/15689447/)

[Cao et al., 2020 - Dynein dysfunction in Parkinson's disease models](https://pubmed.ncbi.nlm.nih.gov/32291087/)

[Dupuis et al., 2009 - Dynein mutations in motor neuron disease](https://pubmed.ncbi.nlm.nih.gov/19240061/)

[Chevalier-Larsen & Holzbaur, 2006 - Axonal transport in neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/16549510/)

[Dagoneau et al., 2009 - DYNC2H1 mutations in SRPS3](https://pubmed.ncbi.nlm.nih.gov/19686095/)

[Huber et al., 2015 - DYNC2H1 in Jeune syndrome](https://pubmed.ncbi.nlm.nih.gov/25944731/)

[Sweeney et al., 2018 - Dynein in neuronal health and disease](https://pubmed.ncbi.nlm.nih.gov/29626934/)

[Gupta et al., 2016 - Axonal transport defects in neurodegenerative disease](https://pubmed.ncbi.nlm.nih.gov/27256559/)

[Hirokawa et al., 2010 - Neuronal transport systems](https://pubmed.ncbi.nlm.nih.gov/20404190/)

[Maday et al., 2014 - Axonal autophagosomal transport](https://pubmed.ncbi.nlm.nih.gov/24436452/)

[Encalada & Goldstein, 2014 - Axonal transport dynamics](https://pubmed.ncbi.nlm.nih.gov/25484938/)

[Schuldt, 2021 - Molecular motors in neuronal disease](https://pubmed.ncbi.nlm.nih.gov/34001475/)

[Ene et al., 2022 - Dynein regulation in transport](https://pubmed.ncbi.nlm.nih.gov/35107892/)

[Olenick et al., 2019 - Dynein-2 and IFT in disease](https://pubmed.ncbi.nlm.nih.gov/30699668/)

[Hammesh et al., 2023 - Dynein mutations and neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/36789654/)

[Rashid et al., 2023 - Therapeutic targeting of axonal transport](https://pubmed.ncbi.nlm.nih.gov/37129876/)

📖 View canonical wiki page →

Related Entities

DYNC2H1

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-dync2h1
kg_node_id	DYNC2H1
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-79d24041f85f
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-dync2h1'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

15%

Debates

0

Incoming

3

Outgoing

10

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1

DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1

Overview

DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 1

Overview

Introduction

Gene Function

Core Motor Protein Function

Retrograde Axonal Transport

Intraflagellar Transport (IFT)

Ciliary Function

Role in Neurodegeneration

Link to Alzheimer's Disease

Link to Parkinson's Disease

Implications for Amyotrophic Lateral Sclerosis (ALS)

Role in Frontotemporal Dementia (FTD)

Other Neurodegenerative Conditions

Expression Pattern

Brain Expression

Cellular Localization

Non-Neuronal Expression

Protein-Protein Interactions

Core Dynein Complex

IFT Components

Regulatory Proteins

Therapeutic Implications

Targeting Axonal Transport

Small Molecule Approaches

Gene Therapy Potential

Mermaid Diagram: Dynein-2 Function in Retrograde Transport

Disease Associations

Short Rib-Polydactyly Syndrome Type 3

Asphyxiating Thoracic Dysplasia (Jeune Syndrome)

Neurodegenerative Diseases

Research Directions

See Also

References

💬 Discussion