GeneBe

DYNC2H1

dynein cytoplasmic 2 heavy chain 1, the group of Dynein 2 complex subunits

Basic information

Region (hg38): 11:103109410-103479863

Previous symbols: [ "DNCH2" ]

Links

ENSG00000187240 ∙ NCBI:79659 ∙ OMIM:603297 ∙ HGNC:2962 ∙ Uniprot:Q8NCM8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • asphyxiating thoracic dystrophy 3 (Definitive), mode of inheritance: AR
  • asphyxiating thoracic dystrophy 3 (Definitive), mode of inheritance: AR
  • Jeune syndrome (Supportive), mode of inheritance: AR
  • short rib-polydactyly syndrome, Majewski type (Supportive), mode of inheritance: AR
  • asphyxiating thoracic dystrophy 3 (Supportive), mode of inheritance: AR
  • short rib-polydactyly syndrome, Verma-Naumoff type (Supportive), mode of inheritance: AR
  • asphyxiating thoracic dystrophy 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Short-rib thoracic dysplasia 3 with or without polydactylyAR/DigenicGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal19442771; 19361615; 21211617; 22499340; 22791528; 22499340
Digenic variants in both NEK1 and DYNC2H1 can result in disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DYNC2H1 gene.

  • Jeune_thoracic_dystrophy (2832 variants)
  • Asphyxiating_thoracic_dystrophy_3 (627 variants)
  • not_provided (511 variants)
  • Inborn_genetic_diseases (499 variants)
  • not_specified (187 variants)
  • DYNC2H1-related_disorder (117 variants)
  • Short_rib-polydactyly_syndrome (73 variants)
  • Retinal_dystrophy (29 variants)
  • Intellectual_disability (14 variants)
  • Optic_atrophy (5 variants)
  • Autosomal_recessive_retinitis_pigmentosa (5 variants)
  • Short_long_bone (3 variants)
  • Narrow_chest (3 variants)
  • Short_ribs (3 variants)
  • Short-rib_thoracic_dysplasia_6_with_or_without_polydactyly (3 variants)
  • Neonatal_respiratory_distress (2 variants)
  • Fetal_growth_restriction (2 variants)
  • Renal_cyst (2 variants)
  • Abnormality_of_the_lung (2 variants)
  • Deformed_rib_cage (2 variants)
  • Bowing_of_the_long_bones (2 variants)
  • Heart,_malformation_of (2 variants)
  • Hirschsprung_disease,_susceptibility_to,_1 (1 variants)
  • Ciliopathy (1 variants)
  • Type_IV_short_rib_polydactyly_syndrome (1 variants)
  • Micrognathia (1 variants)
  • Autosomal_recessive_polycystic_kidney_disease (1 variants)
  • Asphyxiating_thoracic_dystrophy_1 (1 variants)
  • Asphyxiating_thoracic_dystrophy_2 (1 variants)
  • Clinodactyly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYNC2H1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001377.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
16
clinvar
1002
clinvar
10
clinvar
 1031
missense
7
clinvar
114
clinvar
956
clinvar
106
clinvar
3
clinvar
 1186
nonsense
109
clinvar
72
clinvar
3
clinvar
1
clinvar
 185
start loss
1
2
 3
frameshift
99
clinvar
54
clinvar
3
clinvar
 156
splice donor/acceptor (+/-2bp)
13
clinvar
101
clinvar
1
clinvar
 115
Total 229 344 980 1109 14

Highest pathogenic variant AF is 0.000339756

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DYNC2H1protein_codingprotein_codingENST00000398093 90370432
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.14e-441.0012435012871246380.00116
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.90918902.00e+30.9430.00010428122
Missense in Polyphen416557.630.746017790
Synonymous-0.7326986741.040.00003347846
Loss of Function7.121132290.4930.00001273065

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.003020.00292
Ashkenazi Jewish0.001320.00129
East Asian0.0009690.000946
Finnish0.0001420.000139
European (Non-Finnish)0.001370.00123
Middle Eastern0.0009690.000946
South Asian0.001320.00128
Other0.001550.00132

dbNSFP

Source: dbNSFP

Function
FUNCTION: May function as a motor for intraflagellar retrograde transport. Functions in cilia biogenesis. May play a role in transport between endoplasmic reticulum and Golgi or organization of the Golgi in cells (By similarity). {ECO:0000250}.;
Disease
DISEASE: Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) [MIM:613091]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:19361615, ECO:0000269|PubMed:19442771, ECO:0000269|PubMed:22499340, ECO:0000269|PubMed:23456818}. Note=The disease is caused by mutations affecting the gene represented in this entry. In some cases DYNC2H1 mutations result in disease phenotype in the presence of mutations in NEK1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617). {ECO:0000269|PubMed:21211617}.;
Pathway
Salmonella infection - Homo sapiens (human);Phagosome - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Purine metabolism;Intraflagellar transport;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

pRec
0.106

Intolerance Scores

loftool
0.998
rvis_EVS
-0.35
rvis_percentile_EVS
29.56

Haploinsufficiency Scores

pHI
0.120
hipred
Y
hipred_score
0.652
ghis
0.514

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.908

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Dync2h1
Phenotype
cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; respiratory system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype;

Zebrafish Information Network

Gene name
dync2h1
Affected structure
neuromast hair cell
Phenotype tag
abnormal
Phenotype quality
absent

Gene ontology

Biological process
microtubule-based movement;Golgi organization;multicellular organism development;intraciliary retrograde transport;intraciliary transport involved in cilium assembly;cilium assembly
Cellular component
Golgi apparatus;cytoplasmic dynein complex;microtubule;plasma membrane;cilium;axoneme;dynein complex;motile cilium;extracellular exosome;ciliary tip
Molecular function
motor activity;ATP binding;ATP-dependent microtubule motor activity, minus-end-directed;dynein light chain binding;dynein intermediate chain binding;dynein light intermediate chain binding