DYNC2H1: Dynein Cytoplasmic 2 Heavy Chain 1
Key component of intraflagellar transport (IFT) and ciliary motility; mutations cause skeletal ciliopathies
Gene Information Card
| Symbol | DYNC2H1 |
|---|---|
| Full Name | Dynein cytoplasmic 2 heavy chain 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 79659 ncbi.nlm.nih.gov/gene/79659 |
| Ensembl ID | ENSG00000187240 |
| UniProt ID | Q8NCM8 |
| OMIM ID | 603297 |
| HGNC ID | 29662 |
| Aliases | DNCH2, DHC1b, DHC2, DYNC2H1, cDHC2, bA342M3.1 |
Description
DYNC2H1 encodes the heavy chain subunit of cytoplasmic dynein 2, a microtubule-associated motor protein complex that powers retrograde intraflagellar transport (IFT) within cilia. This transport is critical for ciliary assembly, maintenance, and signaling. Mutations in DYNC2H1 disrupt ciliary function and lead to a spectrum of skeletal ciliopathies, most notably short-rib thoracic dysplasia (SRTD) with or without polydactyly, including Jeune syndrome. The gene is ubiquitously expressed, with highest levels in tissues rich in ciliated cells such as lung, kidney, and testis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) | Loss-of-function mutations impair retrograde IFT, causing defective ciliary assembly and skeletal patterning | OMIM #613091; multiple reports in ClinVar and literature |
| Jeune syndrome (asphyxiating thoracic dystrophy) | Biallelic DYNC2H1 mutations disrupt ciliary function in chondrocytes, leading to narrow thorax and short limbs | OMIM #208500; confirmed by sequencing studies |
| Ellis-van Creveld syndrome-like phenotype | Rare DYNC2H1 variants may mimic EVC due to shared ciliary pathway disruption | Case reports in ClinVar |
| Nephronophthisis (NPHP) | Ciliary dysfunction in renal tubular cells leads to cystic kidney disease | Rare association; evidence from functional studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Kidney | 10.8 | Medium |
| Testis | 15.2 | Medium |
| Brain | 6.3 | Low |
| Liver | 4.1 | Low |
| Heart | 5.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | Embryonic kidney; high ciliary activity |
| A549 | 14.2 | Lung carcinoma; ciliated epithelial origin |
| HeLa | 9.8 | Cervical carcinoma; moderate expression |
| HepG2 | 5.1 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.11041C>T (p.Arg3681*) | Nonsense | <0.01% | Premature stop; loss of motor domain function |
| c.10778G>A (p.Arg3593Gln) | Missense | <0.01% | Impaired ATPase activity; reduced retrograde IFT |
| c.10378_10379del (p.Leu3460Valfs*2) | Frameshift | <0.01% | Loss of function; associated with SRTD3 |
| c.11440C>T (p.Arg3814Cys) | Missense | <0.01% | Dominant negative effect in some ciliary assays |
Mutation functional classification
Loss of Function (LOF)
Most DYNC2H1 disease-associated mutations are loss-of-function (nonsense, frameshift, splice-site) leading to truncated or absent protein, impairing retrograde IFT.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in DYNC2H1.
Dominant Negative (DN)
Rare missense variants (e.g., p.Arg3814Cys) may exert dominant-negative effects by disrupting dynein complex assembly.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Intraflagellar transport (IFT) – retrograde
• Ciliary assembly and disassembly
• Hedgehog signaling pathway (ciliary-dependent)
Protein Summary
DYNC2H1 is a large (approximately 530 kDa) protein that forms the heavy chain of the cytoplasmic dynein 2 complex. It contains an N-terminal tail domain for cargo binding and a C-terminal motor domain with AAA+ ATPase activity that generates force along microtubules toward the minus end (retrograde transport). The protein is essential for moving IFT particles and associated cargo from the ciliary tip back to the cell body. Loss of DYNC2H1 function leads to accumulation of IFT particles at the ciliary tip, defective ciliary resorption, and impaired Hedgehog signaling, which underlies the skeletal and renal phenotypes observed in ciliopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DYNC2H1 Knockout HEK293 Cell Line | EDJ-KQ13234 | Human | 79659 | Details Get a Quote |
| DYNC2H1 Knockout HCT 116 Cell Line | EDJ-KQ41389 | Human | 79659 | Details Get a Quote |
| DYNC2H1 Knockout A-549 Cell Line | EDJ-KQ42615 | Human | 79659 | Details Get a Quote |
| DYNC2H1 Knockout HeLa Cell Line | EDJ-KQ42617 | Human | 79659 | Details Get a Quote |
| DYNC2H1 Knockout U-87MG ATCC Cell Line | EDJ-KZ201 | Human | 79659 | Details Get a Quote |
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