DNAH17
Chr 17ARdynein axonemal heavy chain 17
Also known as: DNAHL1, DNEL2, SPGF39
DNAH17 encodes a heavy chain component of outer dynein arms that generates force for microtubule-based movement and is essential for sperm flagellar assembly and beating. Autosomal recessive mutations cause spermatogenic failure 39, a form of male infertility due to impaired sperm motility. The pathogenic mechanism involves gain-of-function mutations that disrupt normal dynein motor protein function in sperm flagella.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
900 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 3 | 0 | 3 |
Likely Pathogenic | 9 | 0 | 3 | 0 | 12 |
VUS | 1 | 459 | 1 | 0 | 461 |
Likely Benign | 0 | 18 | 16 | 72 | 106 |
Benign | 0 | 32 | 189 | 35 | 256 |
Conflicting | — | 2 | |||
| Total | 10 | 509 | 212 | 107 | 840 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
DNAH17 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools