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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DYNC2H1
dynein cytoplasmic 2 heavy chain 1
Chromosome 11 Β· 11q22.3
NCBI Gene: 79659Ensembl: ENSG00000187240.18HGNC: HGNC:2962UniProt: Q8NCM8
95PubMed Papers
21Diseases
0Drugs
569Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
minus-end-directed microtubule motor activityGolgi apparatusprotein bindingcytoplasmic dynein complexasphyxiating thoracic dystrophy 3Jeune syndromeShort rib-polydactyly syndrome, Verma-Naumoff typeshort rib-polydactyly syndrome, Majewski type
✦AI Summary

DYNC2H1 encodes dynein cytoplasmic 2 heavy chain 1, a minus-end-directed microtubule motor protein essential for intraflagellar retrograde transport and cilia biogenesis 1. The protein functions as a motor component of the cytoplasmic dynein complex, facilitating transport of proteins along ciliary axonemes and potentially regulating intracellular trafficking between the endoplasmic reticulum and Golgi apparatus. DYNC2H1 mutations cause a spectrum of skeletal ciliopathies characterized by profound skeletal abnormalities. Short-rib thoracic dysplasia (SRTD) with or without polydactyly, formerly known as asphyxiating thoracic dystrophy (Jeune syndrome), represents the primary disease association, with approximately half of SRPS cases linked to DYNC2H1 variants 2. Clinical presentations range from perinatal lethal forms to milder phenotypes, with variable severity correlating with antenatal presentation timing and femur shortening rather than genotype 3. Beyond skeletal ciliopathies, DYNC2H1 mutations have been identified in Ellis-van Creveld syndrome and lingual hamartoma, suggesting broader developmental roles 14. Compound heterozygous variants and digenic inheritance involving DYNC2H1 and NEK1 contribute to disease pathogenesis 5. Early prenatal diagnosis through exome sequencing enables prognostic assessment and family genetic counseling for affected pregnancies.

Sources cited
1
DYNC2H1 variants cause skeletal ciliopathies with expanded clinical spectrum including short rib-polydactyly, ATD, and Ellis-van Creveld syndrome
PMID: 36599940
2
Approximately half of SRPS cases are associated with DYNC2H1 variants; digenic variants with NEK1 also contribute
PMID: 40339774
3
DYNC2H1-related SRTD shows significant phenotypic variability with severity correlating to antenatal presentation and femur shortening, not genotype
PMID: 40250984
4
DYNC2H1 mutations affect cilium assembly and Hedgehog signaling in lingual hamartoma development
PMID: 36087272
5
NEK1 and DYNC2H1 mutations identified in short rib polydactyly Majewski type; digenic inheritance possible
PMID: 22499340
6
DYNC2H1 is one of at least 17 genes associated with asphyxiating thoracic dystrophy; prenatal diagnosis possible via rapid WES
PMID: 35893076
Disease Associationsβ“˜21
asphyxiating thoracic dystrophy 3Open Targets
0.86Strong
Jeune syndromeOpen Targets
0.71Strong
Short rib-polydactyly syndrome, Verma-Naumoff typeOpen Targets
0.71Strong
short rib-polydactyly syndrome, Majewski typeOpen Targets
0.67Moderate
autosomal recessive retinitis pigmentosaOpen Targets
0.46Moderate
Retinal dystrophyOpen Targets
0.44Moderate
Narrow chestOpen Targets
0.44Moderate
Abnormality of the skeletal systemOpen Targets
0.43Moderate
Bowing of the long bonesOpen Targets
0.43Moderate
fetal growth restrictionOpen Targets
0.43Moderate
IMAGe syndromeOpen Targets
0.43Moderate
short-rib thoracic dysplasia 6 with or without polydactylyOpen Targets
0.42Moderate
short rib dysplasiaOpen Targets
0.37Weak
type 2 diabetes mellitusOpen Targets
0.37Weak
retinitis pigmentosaOpen Targets
0.37Weak
short rib-polydactyly syndromeOpen Targets
0.34Weak
genetic disorderOpen Targets
0.34Weak
arrhythmogenic right ventricular dysplasia 10Open Targets
0.34Weak
autosomal dominant Robinow syndromeOpen Targets
0.34Weak
Robinow syndromeOpen Targets
0.34Weak
Short-rib thoracic dysplasia 3 with or without polydactylyUniProt
Pathogenic Variants569
NM_001377.3(DYNC2H1):c.10112C>G (p.Ser3371Ter)Pathogenic
Asphyxiating thoracic dystrophy 3|Jeune thoracic dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 3371
NM_001377.3(DYNC2H1):c.3859C>T (p.Arg1287Ter)Pathogenic
Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3
β˜…β˜…β˜†β˜†2026β†’ Residue 1287
NM_001377.3(DYNC2H1):c.10648T>C (p.Ser3550Pro)Pathogenic
Inborn genetic diseases|Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3|not provided|DYNC2H1-related disorder|Retinal dystrophy|Retinitis pigmentosa;Asphyxiating thoracic dystrophy 4
β˜…β˜…β˜†β˜†2026β†’ Residue 3550
NM_001377.3(DYNC2H1):c.10573C>T (p.Arg3525Ter)Pathogenic
Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 3525
NM_001377.3(DYNC2H1):c.4458del (p.Phe1486fs)Pathogenic
Asphyxiating thoracic dystrophy 3|Jeune thoracic dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 1486
NM_001377.3(DYNC2H1):c.5984C>T (p.Ala1995Val)Pathogenic
Jeune thoracic dystrophy|not provided|Asphyxiating thoracic dystrophy 3
β˜…β˜…β˜†β˜†2026β†’ Residue 1995
NM_001377.3(DYNC2H1):c.9044A>G (p.Asp3015Gly)Pathogenic
Asphyxiating thoracic dystrophy 3|not provided|Jeune thoracic dystrophy|Fetal growth restriction;Bowing of the long bones;Narrow chest|DYNC2H1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 3015
NM_001377.3(DYNC2H1):c.5983G>A (p.Ala1995Thr)Pathogenic
not provided|Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3|DYNC2H1-related disorder|Autosomal dominant Robinow syndrome 2
β˜…β˜…β˜†β˜†2026β†’ Residue 1995
NM_001377.3(DYNC2H1):c.12480dup (p.Gln4161fs)Pathogenic
Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3
β˜…β˜…β˜†β˜†2026β†’ Residue 4161
NM_001377.3(DYNC2H1):c.4698del (p.Gln1566fs)Pathogenic
not provided|Asphyxiating thoracic dystrophy 3|Jeune thoracic dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 1566
NM_001377.3(DYNC2H1):c.11650-1G>APathogenic
not provided|Jeune thoracic dystrophy
β˜…β˜…β˜†β˜†2026
NM_001377.3(DYNC2H1):c.4219C>T (p.Gln1407Ter)Pathogenic
Asphyxiating thoracic dystrophy 3|Jeune thoracic dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 1407
NM_001377.3(DYNC2H1):c.2692C>T (p.Arg898Ter)Pathogenic
DYNC2H1-related disorder|Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3
β˜…β˜…β˜†β˜†2026β†’ Residue 898
NM_001377.3(DYNC2H1):c.10322T>C (p.Leu3441Pro)Pathogenic
Asphyxiating thoracic dystrophy 3|Jeune thoracic dystrophy|Short-rib thoracic dysplasia 6 with or without polydactyly|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 3441
NM_001377.3(DYNC2H1):c.9565C>T (p.Gln3189Ter)Pathogenic
Asphyxiating thoracic dystrophy 3|Jeune thoracic dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 3189
NM_001377.3(DYNC2H1):c.4699C>G (p.Leu1567Val)Pathogenic
not provided|Asphyxiating thoracic dystrophy 3|Jeune thoracic dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 1567
NM_001377.3(DYNC2H1):c.10142C>T (p.Pro3381Leu)Pathogenic
not specified|Jeune thoracic dystrophy|not provided|Asphyxiating thoracic dystrophy 3
β˜…β˜…β˜†β˜†2026β†’ Residue 3381
NM_001377.3(DYNC2H1):c.1151C>T (p.Ala384Val)Pathogenic
Jeune thoracic dystrophy|not provided|Asphyxiating thoracic dystrophy 3
β˜…β˜…β˜†β˜†2026β†’ Residue 384
NM_001377.3(DYNC2H1):c.10024C>T (p.Arg3342Ter)Pathogenic
not provided|Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3
β˜…β˜…β˜†β˜†2025β†’ Residue 3342
NM_001377.3(DYNC2H1):c.6910G>A (p.Ala2304Thr)Pathogenic
not provided|Jeune thoracic dystrophy|Asphyxiating thoracic dystrophy 3|DYNC2H1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 2304
View on ClinVar β†—
Related Genes
TTC21BProtein interaction100%TUBBProtein interaction99%TUBB4BProtein interaction99%TUBA1BProtein interaction98%DYNLL2Protein interaction97%TUBB6Protein interaction97%
Tissue Expression6 tissues
Ovary
100%
Heart
38%
Brain
37%
Lung
32%
Bone Marrow
20%
Liver
8%
Gene Interaction Network
Click a node to explore
DYNC2H1TTC21BTUBBTUBB4BTUBA1BDYNLL2TUBB6
PROTEIN STRUCTURE
Preparing viewer…
PDB4RH7 Β· 3.41 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.86LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.78 [0.71–0.86]
RankingsWhere DYNC2H1 stands among ~20K protein-coding genes
  • #5,028of 20,598
    Most Researched95 Β· top quartile
  • #88of 5,498
    Most Pathogenic Variants569 Β· top 5%
  • #7,515of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedDYNC2H1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies.
PMID: 29068549
Hum Mutat Β· 2018
1.00
2
Clinical variability in DYNC2H1-related skeletal ciliopathies includes Ellis-van Creveld syndrome.
PMID: 36599940
Eur J Hum Genet Β· 2023
0.90
3
Pathogenic variant of DYNC2H1 associated with lingual hamartoma in a Chinese pedigree.
PMID: 36087272
J Oral Pathol Med Β· 2022
0.80
4
Expanding the genetic spectrum of short rib polydactyly syndrome: Novel DYNC2H1 variants and functional insights.
PMID: 40339774
Bone Β· 2025
0.70
5
Sequential prenatal diagnosis of fetal skeletal dysplasia: A cohort study.
PMID: 40035361
Acta Obstet Gynecol Scand Β· 2025
0.60