DNAH5

dynein axonemal heavy chain 5, the group of Dyneins, axonemal outer arm complex subunits

Basic information

Region (hg38): 5:13690327-14011818

Links

ENSG00000039139 ∙ NCBI:1767 ∙ OMIM:603335 ∙ HGNC:2950 ∙ Uniprot:Q8TE73 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the DNAH5 gene.

• Primary ciliary dyskinesia (4103 variants)
• Primary ciliary dyskinesia 3 (855 variants)
• not provided (547 variants)
• not specified (230 variants)
• Inborn genetic diseases (132 variants)
• DNAH5-related condition (30 variants)
• Infertility disorder (3 variants)
• Heterotaxy (2 variants)
• Kartagener syndrome (2 variants)
• Male infertility (1 variants)
• Cough;Anomalous origin of coronary artery from the pulmonary artery;Clinodactyly of the 5th finger (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	1		14	1426	19	1460
missense	9	22	753	341	68	1193
nonsense	193	76	1			270
start loss						0
frameshift	196	160				356
inframe indel		4	6			10
splice donor/acceptor (+/-2bp)	33	91	1	1		126
splice region	2	2	55	239	23	321
non coding			36	389	262	687
Total	432	353	811	2157	349

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: gnomAD

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: dbNSFP

• 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