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

ENSG00000256061 ∙ NCBI:161582 ∙ OMIM:608706 ∙ HGNC:21493 ∙ Uniprot:Q8WXU2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary ciliary dyskinesia 25 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• primary ciliary dyskinesia 25 (Definitive), mode of inheritance: AR
• primary ciliary dyskinesia 25 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the DNAAF4 gene.

• not_provided (214 variants)
• Inborn_genetic_diseases (69 variants)
• Primary_ciliary_dyskinesia_25 (24 variants)
• Dyslexia,_susceptibility_to,_1 (12 variants)
• DNAAF4-related_disorder (8 variants)
• Primary_ciliary_dyskinesia (8 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. These statistics are base on transcript: NM_000130810.4. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	43	1	46
missense	1	2	119	3	2	127
nonsense	5	5				10
start loss		1				1
frameshift	12	7				19
splice donor/acceptor (+/-2bp)	6	3	1			10
Total	24	18	122	46	3

Highest pathogenic variant AF is 0.00015200379

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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_gene_trap: N

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