DNAH1

dynein axonemal heavy chain 1, the group of Dyneins, axonemal inner arm I1/f complex subunits

Basic information

Region (hg38): 3:52316319-52400492

Links

ENSG00000114841 ∙ NCBI:25981 ∙ OMIM:603332 ∙ HGNC:2940 ∙ Uniprot:Q9P2D7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ciliary dyskinesia, primary, 37 (Moderate), mode of inheritance: AR
• primary ciliary dyskinesia (Supportive), mode of inheritance: AD
• non-syndromic male infertility due to sperm motility disorder (Supportive), mode of inheritance: AR
• spermatogenic failure 18 (Strong), mode of inheritance: AR
• ciliary dyskinesia, primary, 37 (Strong), mode of inheritance: AR
• spermatogenic failure 18 (Definitive), mode of inheritance: AR
• ciliary dyskinesia, primary, 37 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ciliary dyskinesia, primary, 37	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; Individuals may require surgery or other interventions related to congenital cardiac malformations	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Genitourinary; Pulmonary	24360805; 25927852; 27573432; 29449551

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAH1 gene.

• Spermatogenic failure 18;Ciliary dyskinesia, primary, 37 (37 variants)
• Ciliary dyskinesia, primary, 37;Spermatogenic failure 18 (8 variants)
• Spermatogenic failure 18 (3 variants)
• not provided (1 variants)
• Ciliary dyskinesia, primary, 37 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAH1 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			14	516	37	567
missense		5	901	60	23	989
nonsense	21	5				26
start loss						0
frameshift	25	8	1			34
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)	1	22	2		1	26
splice region			36	91	6	133
non coding			13	257	73	343
Total	47	40	935	834	134

Highest pathogenic variant AF is 0.000223

Variants in DNAH1

This is a list of pathogenic ClinVar variants found in the DNAH1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-52322110-G-A			Likely benign (Jul 10, 2018)
3-52322448-G-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Dec 06, 2023)
3-52322455-A-C		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (Mar 04, 2022)
3-52322459-G-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (Jul 05, 2022)
3-52322484-C-T		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Mar 29, 2018)
3-52322488-C-T		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37 • DNAH1-related disorder • Spermatogenic failure 18	Conflicting classifications of pathogenicity (Apr 04, 2024)
3-52322493-C-T		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Sep 05, 2023)
3-52322496-A-G		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Mar 18, 2023)
3-52322509-G-T		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (May 08, 2023)
3-52322510-C-T		not specified	Uncertain significance (May 03, 2023)
3-52322519-T-C		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37 • Primary ciliary dyskinesia	Uncertain significance (Sep 01, 2021)
3-52322554-C-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (Jul 12, 2022)
3-52322555-C-T		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (Jul 20, 2022)
3-52322556-G-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Dec 18, 2023)
3-52322559-G-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Nov 05, 2021)
3-52322559-G-C		Ciliary dyskinesia, primary, 37;Spermatogenic failure 18	Likely benign (Dec 15, 2023)
3-52322566-C-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (Nov 23, 2022)
3-52322571-A-G		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Mar 15, 2021)
3-52322585-G-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (Jul 08, 2023)
3-52322592-A-G		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Feb 10, 2022)
3-52322593-A-G		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Uncertain significance (Mar 27, 2022)
3-52322609-AC-A		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Pathogenic (May 23, 2023)
3-52322612-C-T		Ciliary dyskinesia, primary, 37;Spermatogenic failure 18	Uncertain significance (Jan 31, 2018)
3-52322639-C-T		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Likely benign (Jan 18, 2024)
3-52322641-GCC-G		Spermatogenic failure 18;Ciliary dyskinesia, primary, 37	Pathogenic (Sep 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAH1	protein_coding	protein_coding	ENST00000420323	77	84173

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.50e-26	1.00	124562	0	438	125000	0.00175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	2297	2.47e+3	0.931	0.000155	27943
Missense in Polyphen		656	849.98	0.77178		9606
Synonymous	-0.815	1046	1.01e+3	1.03	0.0000673	8100
Loss of Function	8.06	83	209	0.398	0.0000109	2314

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00212	0.00206
Ashkenazi Jewish	0.000998	0.000994
East Asian	0.00359	0.00345
Finnish	0.00231	0.00228
European (Non-Finnish)	0.00201	0.00197
Middle Eastern	0.00359	0.00345
South Asian	0.00120	0.00118
Other	0.00134	0.00131

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Force generating protein of cilia required for sperm flagellum motility. 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 in spermatozoa for the formation of the inner dynein arms and biogenesis of the axoneme (PubMed:24360805). {ECO:0000250|UniProtKB:Q91XQ0, ECO:0000269|PubMed:24360805}.
• Disease: DISEASE: Spermatogenic failure 18 (SPGF18) [MIM:617576]: An infertility disorder caused by spermatogenesis defects and characterized by abnormally shaped spermatozoa in the semen of affected individuals. SPGF18 patients present with primary infertility and multiple morphological abnormalities of sperm flagella that result in impaired sperm mobility. Abnormalities include absent, short, coiled, bent, and irregular flagella. SPGF18 inheritance is autosomal recessive. {ECO:0000269|PubMed:24360805, ECO:0000269|PubMed:27798045, ECO:0000269|PubMed:28552195, ECO:0000269|PubMed:29449551}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ciliary dyskinesia, primary, 37 (CILD37) [MIM:617577]: A form of primary ciliary dyskinesia, 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. Some patients exhibit randomization of left-right body asymmetry and situs inversus. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome. CILD37 inheritance is autosomal recessive. {ECO:0000269|PubMed:25927852}. 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)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.767
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.64

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.448
• ghis: 0.558

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.447

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	High	Medium	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Dnah1
• Phenotype: respiratory system phenotype; reproductive system phenotype

Gene ontology

• Biological process: epithelial cilium movement;microtubule-based movement;sperm axoneme assembly;flagellated sperm motility;inner dynein arm assembly;cilium-dependent cell motility;cilium movement involved in cell motility
• Cellular component: axonemal dynein complex;microtubule;axoneme;dynein complex;sperm flagellum;inner dynein arm
• Molecular function: microtubule 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