DNAH8

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

Basic information

Region (hg38): 6:38715311-39030792

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 15.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_001206927.2	NP_001193856.1	92	yes	-
ENST00000327475.11	ENSP00000333363.7	92	yes	-
NM_001371.4	NP_001362.2	89	-	-
ENST00000373278.8	ENSP00000362375.4	4	-	-

Phenotypes

GenCC

Source: genCC

• 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
• spermatogenic failure 5 (Moderate), 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 (2034 variants)
• not_specified (650 variants)
• not_provided (207 variants)
• DNAH8-related_disorder (67 variants)
• Spermatogenic_failure_46 (59 variants)
• Recurrent_infections (1 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
• Prostate_cancer (1 variants)
• Autism (1 variants)
• Recurrent_infections_of_the_middle_ear (1 variants)
• Inherited_obesity (1 variants)
• Recurrent_respiratory_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. These statistics are base on transcript: NM_001206927.2. 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			8	570	34	612
missense	1		1146	65	18	1230
nonsense	49	8	5			62
start loss			1			1
frameshift	63	6	3			72
splice donor/acceptor (+/-2bp)	2	33	9		1	45
Total	115	47	1172	635	53

Highest pathogenic variant AF is 0.00022049021

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
		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

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

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