DNAH5
dynein axonemal heavy chain 5, the group of Dyneins, axonemal outer arm complex subunits
Basic information
Region (hg38): 5:13690328-14011818
Links
Phenotypes
GenCC
Source:
- primary ciliary dyskinesia 3 (Strong), mode of inheritance: AR
- primary ciliary dyskinesia 3 (Strong), mode of inheritance: AR
- primary ciliary dyskinesia 3 (Strong), mode of inheritance: AR
- primary ciliary dyskinesia (Supportive), mode of inheritance: AD
- primary ciliary dyskinesia 3 (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Ciliary dyskinesia, primary, 3 | AR | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Pulmonary | Pulmonary and audiologic surveillance may be beneficial to assess respiratory and hearing function and institute early management measures; In order to facilitate mucus clearance, aggressive interventions (eg, chest percussion and oscillatory vest), as well as vaccinations and early and aggressive treatment of respiratory infections may be beneficial, though measures including lobectomy or lung transplantation may be necessary; Individuals may require surgery or other interventions related to congenital cardiac malformations | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Pulmonary | 11788826; 16627867; 19300264; 19357118; 20301301; 22416021; 22499950 |
ClinVar
This is a list of variants' phenotypes submitted to
- Primary ciliary dyskinesia (494 variants)
- Primary ciliary dyskinesia 3 (38 variants)
- not provided (19 variants)
- DNAH5-related disorder (6 variants)
- Inborn genetic diseases (3 variants)
- Heterotaxy (2 variants)
- Kartagener syndrome (2 variants)
- Male infertility (1 variants)
- Respiratory ciliopathies including non-CF bronchiectasis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAH5 gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 13 | 1651 | 17 | 1682 | ||
| missense | 10 | 27 | 786 | 413 | 67 | 1303 |
| nonsense | 221 | 77 | 299 | |||
| start loss | 0 | |||||
| frameshift | 236 | 160 | 396 | |||
| inframe indel | 11 | |||||
| splice donor/acceptor (+/-2bp) | 36 | 107 | 145 | |||
| splice region | 2 | 3 | 51 | 285 | 22 | 363 |
| non coding | 33 | 665 | 267 | 965 | ||
| Total | 506 | 374 | 840 | 2730 | 351 |
Highest pathogenic variant AF is 0.000191
Variants in DNAH5
This is a list of pathogenic ClinVar variants found in the DNAH5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 5-13690332-G-A | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13690371-C-T | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13690393-A-T | Primary ciliary dyskinesia 3 | Benign (Jan 13, 2018) | ||
| 5-13690478-C-T | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-13690482-G-A | Primary ciliary dyskinesia 3 | Likely benign (Jan 12, 2018) | ||
| 5-13690595-G-A | Primary ciliary dyskinesia 3 | Likely benign (Apr 27, 2017) | ||
| 5-13690623-C-A | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-13690642-A-C | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13690686-A-T | Primary ciliary dyskinesia 3 | Uncertain significance (Mar 30, 2018) | ||
| 5-13690828-G-A | Primary ciliary dyskinesia 3 | Likely benign (Jan 12, 2018) | ||
| 5-13690865-A-G | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-13690936-T-C | Primary ciliary dyskinesia 3 | Benign (Jan 13, 2018) | ||
| 5-13691064-T-C | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 12, 2018) | ||
| 5-13691093-T-C | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691101-A-G | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691182-T-C | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691209-C-T | Primary ciliary dyskinesia 3 | Benign (Apr 27, 2017) | ||
| 5-13691287-T-C | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691335-C-G | Primary ciliary dyskinesia 3 | Benign (Jan 12, 2018) | ||
| 5-13691421-C-T | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691539-C-T | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691557-C-T | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691558-G-A | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691629-C-T | Primary ciliary dyskinesia 3 | Uncertain significance (Jan 13, 2018) | ||
| 5-13691635-C-T | Primary ciliary dyskinesia 3 | Uncertain significance (Mar 30, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DNAH5 | protein_coding | protein_coding | ENST00000265104 | 79 | 254213 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.86e-64 | 1.00 | 125224 | 2 | 522 | 125748 | 0.00209 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.771 | 2582 | 2.47e+3 | 1.04 | 0.000144 | 30623 |
| Missense in Polyphen | 227 | 247.32 | 0.91783 | 2891 | ||
| Synonymous | -1.16 | 962 | 917 | 1.05 | 0.0000543 | 8663 |
| Loss of Function | 5.61 | 141 | 233 | 0.604 | 0.0000132 | 2741 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00396 | 0.00396 |
| Ashkenazi Jewish | 0.000795 | 0.000794 |
| East Asian | 0.00185 | 0.00185 |
| Finnish | 0.00287 | 0.00282 |
| European (Non-Finnish) | 0.00235 | 0.00232 |
| Middle Eastern | 0.00185 | 0.00185 |
| South Asian | 0.00138 | 0.00137 |
| Other | 0.00196 | 0.00196 |
dbNSFP
Source:
- Function
- FUNCTION: Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required for structural and functional integrity of the cilia of ependymal cells lining the brain ventricles.;
- Disease
- DISEASE: Ciliary dyskinesia, primary, 3 (CILD3) [MIM:608644]: A disorder characterized by abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit randomization of left-right body asymmetry and situs inversus, due to dysfunction of monocilia at the embryonic node. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. {ECO:0000269|PubMed:11062149, ECO:0000269|PubMed:11788826, ECO:0000269|PubMed:16627867, ECO:0000269|PubMed:25186273}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Huntington,s disease - Homo sapiens (human);lissencephaly gene (lis1) in neuronal migration and development
(Consensus)
Intolerance Scores
- loftool
- 0.942
- rvis_EVS
- -0.18
- rvis_percentile_EVS
- 40.16
Haploinsufficiency Scores
- pHI
- 0.102
- hipred
- N
- hipred_score
- 0.466
- ghis
- 0.442
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.121
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Dnah5
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; hematopoietic system 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); digestive/alimentary 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); hearing/vestibular/ear phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype;
Gene ontology
- Biological process
- cilium movement;microtubule-based movement;determination of left/right symmetry;heart development;lateral ventricle development;flagellated sperm motility;outer dynein arm assembly;cilium assembly
- Cellular component
- microtubule;axoneme;dynein complex;outer dynein arm;9+2 motile cilium
- Molecular function
- ATP binding;ATP-dependent microtubule motor activity, minus-end-directed;dynein light chain binding;dynein intermediate chain binding;dynein light intermediate chain binding