DNAAF4
dynein axonemal assembly factor 4, the group of Tetratricopeptide repeat domain containing|Axonemal dynein assembly factors
Basic information
Region (hg38): 15:55410525-55508234
Previous symbols: [ "DYX1C1" ]
Links
Phenotypes
GenCC
Source:
- primary ciliary dyskinesia 25 (Strong), mode of inheritance: AR
- primary ciliary dyskinesia (Supportive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Ciliary dyskinesia, primary 25 | 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 | 23872636 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (16 variants)
- Primary ciliary dyskinesia 25 (6 variants)
- Primary ciliary dyskinesia (3 variants)
- Dyslexia, susceptibility to, 1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAAF4 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 | 34 | 36 | ||||
| missense | 92 | 103 | ||||
| nonsense | 10 | |||||
| start loss | 1 | |||||
| frameshift | 11 | 15 | ||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| splice region | 4 | 8 | 12 | |||
| non coding | 31 | 41 | 74 | |||
| Total | 18 | 13 | 97 | 70 | 48 |
Highest pathogenic variant AF is 0.0000858
Variants in DNAAF4
This is a list of pathogenic ClinVar variants found in the DNAAF4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| DNAAF4 | protein_coding | protein_coding | ENST00000321149 | 9 | 97710 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 9.72e-10 | 0.503 | 125702 | 0 | 46 | 125748 | 0.000183 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.867 | 251 | 215 | 1.17 | 0.0000111 | 2763 |
| Missense in Polyphen | 103 | 78.443 | 1.3131 | 925 | ||
| Synonymous | -1.35 | 89 | 74.2 | 1.20 | 0.00000372 | 736 |
| Loss of Function | 1.14 | 17 | 22.9 | 0.744 | 0.00000123 | 296 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000307 | 0.000301 |
| Ashkenazi Jewish | 0.000107 | 0.0000992 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.000370 | 0.000370 |
| European (Non-Finnish) | 0.000204 | 0.000202 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.000133 | 0.000131 |
| Other | 0.000171 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Axonemal dynein assembly factor required for ciliary motility. Involved in neuronal migration during development of the cerebral neocortex. May regulate the stability and proteasomal degradation of the estrogen receptors that play an important role in neuronal differentiation, survival and plasticity. {ECO:0000269|PubMed:19423554, ECO:0000269|PubMed:23872636}.;
- Disease
- DISEASE: Ciliary dyskinesia, primary, 25 (CILD25) [MIM:615482]: 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. Patients may 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:23872636, ECO:0000269|PubMed:25186273}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0841
Intolerance Scores
- loftool
- rvis_EVS
- 1.09
- rvis_percentile_EVS
- 91.85
Haploinsufficiency Scores
- pHI
- 0.0983
- hipred
- N
- hipred_score
- 0.170
- ghis
- 0.424
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- gene_indispensability_score
Mouse Genome Informatics
- Gene name
- Dyx1c1
- Phenotype
- respiratory system phenotype; 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); 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); hematopoietic system 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); digestive/alimentary phenotype; immune system phenotype; skeleton phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- dnaaf4
- Affected structure
- pronephric glomerulus
- Phenotype tag
- abnormal
- Phenotype quality
- decreased thickness
Gene ontology
- Biological process
- neuron migration;cilium movement;epithelial cilium movement;determination of left/right symmetry;heart development;regulation of intracellular estrogen receptor signaling pathway;outer dynein arm assembly;inner dynein arm assembly;regulation of proteasomal protein catabolic process
- Cellular component
- nucleus;cytoplasm;centrosome;cytosol;plasma membrane;non-motile cilium
- Molecular function
- protein binding;estrogen receptor binding