DNAH2

Chr 17AR

dynein axonemal heavy chain 2

DNAH2 encodes a dynein heavy chain protein that functions as part of the axonemal inner dynein arm complex, serving as a microtubule-based molecular motor with ATPase activity that converts ATP energy into ciliary bending through microtubule sliding. Biallelic mutations cause autosomal recessive spermatogenic failure 45, characterized by male infertility due to impaired sperm motility. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.563).

OMIMResearchSummary from OMIM, UniProt
GOFmechanismARLOEUF 0.561 OMIM phenotype
Clinical SummaryDNAH2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.000
Z-score 7.41
OE 0.48 (0.410.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.88Z-score
OE missense 0.90 (0.860.93)
2317 obs / 2586.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.410.56)
00.351.4
Missense OE0.90 (0.860.93)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 115 / 238.4Missense obs/exp: 2317 / 2586.5Syn Z: -0.29
DN
0.6064th %ile
GOF
0.7125th %ile
LOF
0.2287th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DNAH2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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