DNAH8

dynein axonemal heavy chain 8, the group of Dyneins, axonemal outer arm complex subunits

Basic information

Region (hg38): 6:38715310-39030792

Links

ENSG00000124721 ∙ NCBI:1769 ∙ OMIM:603337 ∙ HGNC:2952 ∙ Uniprot:Q96JB1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 5 (Moderate), mode of inheritance: AR
• spermatogenic failure 46 (Strong), mode of inheritance: AR
• primary ciliary dyskinesia (Disputed Evidence), mode of inheritance: AR
• spermatogenic failure 46 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 46	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary	32619401; 32681648

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DNAH8 gene.

• Primary ciliary dyskinesia (1397 variants)
• not provided (353 variants)
• Inborn genetic diseases (209 variants)
• Spermatogenic failure 46 (32 variants)
• not specified (19 variants)
• DNAH8-related condition (11 variants)
• Recurrent respiratory infections;Recurrent infections of the middle ear (1 variants)
• Recurrent infections (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DNAH8 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			10	326	48	384
missense			733	40	30	803
nonsense	29	1	1			31
start loss			1			1
frameshift	24	3				27
inframe indel			9			9
splice donor/acceptor (+/-2bp)	1	16	2		1	20
splice region			29	40	12	81
non coding			8	139	270	417
Total	54	20	764	505	349

Highest pathogenic variant AF is 0.000184

Variants in DNAH8

This is a list of pathogenic ClinVar variants found in the DNAH8 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-38722576-G-GT			Benign (Nov 10, 2018)
6-38722577-G-GTGT			Benign (May 11, 2021)
6-38722577-G-GTGTGT			Benign (May 25, 2021)
6-38722581-G-T			Benign (May 11, 2021)
6-38722583-G-T			Benign (May 11, 2021)
6-38722585-T-G			Benign (May 11, 2021)
6-38722587-T-G			Benign (May 11, 2021)
6-38722801-C-T		DNAH8-related disorder	Likely benign (Sep 03, 2019)
6-38722804-CGGGGGAT-C			Uncertain significance (Feb 01, 2023)
6-38722815-G-A		Primary ciliary dyskinesia	Likely benign (Mar 10, 2022)
6-38722815-G-C		Primary ciliary dyskinesia	Uncertain significance (Mar 13, 2019)
6-38722818-G-A		Primary ciliary dyskinesia	Likely benign (Aug 16, 2022)
6-38722833-C-A		Primary ciliary dyskinesia	Likely benign (Sep 19, 2023)
6-38722833-C-T		Primary ciliary dyskinesia	Uncertain significance (Jan 01, 2020)
6-38722842-T-G		Primary ciliary dyskinesia	Likely benign (Jun 15, 2023)
6-38722846-G-A		Primary ciliary dyskinesia	Uncertain significance (Sep 27, 2022)
6-38722847-G-A		not specified	Likely benign (Nov 08, 2021)
6-38722851-A-C		Primary ciliary dyskinesia	Likely benign (Apr 18, 2021)
6-38722852-G-A		not specified	Uncertain significance (May 04, 2022)
6-38722856-C-T		Primary ciliary dyskinesia	Likely benign (Dec 11, 2023)
6-38722877-C-A		Primary ciliary dyskinesia	Uncertain significance (Jun 04, 2021)
6-38722881-C-T		Primary ciliary dyskinesia	Likely benign (Aug 10, 2023)
6-38722893-A-G		Primary ciliary dyskinesia	Likely benign (Sep 07, 2022)
6-38722911-G-A		Primary ciliary dyskinesia	Likely benign (Aug 10, 2023)
6-38722915-C-T		Primary ciliary dyskinesia • Spermatogenic failure 46	Uncertain significance (Mar 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DNAH8	protein_coding	protein_coding	ENST00000359357	89	315185

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-60	1.00	123819	36	1893	125748	0.00770

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	2129	2.29e+3	0.929	0.000121	29652
Missense in Polyphen		827	966.06	0.85605		12841
Synonymous	0.438	792	808	0.980	0.0000434	8199
Loss of Function	5.85	136	232	0.586	0.0000120	3006

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0790	0.0774
Ashkenazi Jewish	0.000828	0.000794
East Asian	0.00154	0.00152
Finnish	0.000557	0.000554
European (Non-Finnish)	0.00411	0.00404
Middle Eastern	0.00154	0.00152
South Asian	0.00264	0.00252
Other	0.00309	0.00294

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. Involved in sperm motility; implicated in sperm flagellar assembly (By similarity). {ECO:0000250}.
• Pathway: Huntington,s disease - Homo sapiens (human);lissencephaly gene (lis1) in neuronal migration and development (Consensus)

Recessive Scores

• pRec: 0.0968

Haploinsufficiency Scores

• pHI: 0.338
• hipred: N
• hipred_score: 0.414

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.203

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dnah8

Gene ontology

• Biological process: microtubule-based movement;outer dynein arm assembly;cilium-dependent cell motility
• Cellular component: axonemal dynein complex;microtubule;dynein complex;outer 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