DNAH2

Chr 17AR

dynein axonemal heavy chain 2

Also known as: DNAHC2, DNHD3, SPGF45

NCBI Gene: 146754ENSG00000183914UniProt: Q9P225

Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[supplied by OMIM, Mar 2008]

Primary Disease Associations & Inheritance

Spermatogenic failure 45MIM #619094
AR
414
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— DNAH2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 338 VUS of 414 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.56LOEUF
pLI 0.000
Z-score 7.41
OE 0.48 (0.41–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.88Z-score
OE missense 0.90 (0.86–0.93)
2317 obs / 2586.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.48 (0.41–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.86–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 115 / 238.4Missense obs/exp: 2317 / 2586.5Syn Z: -0.29

ClinVar Variant Classifications

414 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic1
VUS338
Likely Benign26
Benign24
Conflicting2
23
Pathogenic
1
Likely Pathogenic
338
VUS
26
Likely Benign
24
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
19
0
23
Likely Pathogenic
0
0
1
0
1
VUS
0
334
4
0
338
Likely Benign
0
21
1
4
26
Benign
0
10
5
9
24
Conflicting
—2
Total03693013414

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spermatogenic failure 45

MIM #619094

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Systematic molecular analyses for 115 karyotypically normal men with isolated non-obstructive azoospermia.
Muranishi Y et al.·Hum Reprod
2024
DNAH2 is a novel candidate gene associated with multiple morphological abnormalities of the sperm flagella.
Li Y et al.·Clin Genet
2019
Novel bi-allelic variants in DNAH2 cause severe asthenoteratozoospermia with multiple morphological abnormalities of the flagella.
Gao Y et al.·Reprod Biomed Online
2021
Patients with mutations in DNAH2, DNAH6 and DNAH10 causing multiple morphological abnormalities of human sperm flagella achieve good ICSI outcomes.
Li X et al.·Reprod Biomed Online
2025Cohort
Identifying potential genetic biomarkers for sperm dysfunction through whole-genome sequencing.
Khan MR et al.·Sci Rep
2025
Age-related mutations and chronic myelomonocytic leukemia.
Mason CC et al.·Leukemia
2016
Genetic and transcriptional insights into immune checkpoint blockade response and survival: lessons from melanoma and beyond.
Wen J et al.·J Transl Med
2025
Phenotypes and genotypes in non-consanguineous and consanguineous primary microcephaly: High incidence of epilepsy.
Duerinckx S et al.·Mol Genet Genomic Med
2021
Somatic variants and frequencies of familial myeloma germline predisposition genes among patients within the CoMMpass dataset.
Akkus E et al.·Expert Rev Hematol
2026Cohort
Identification of novel rare variants for anxiety: an exome-wide association study in the UK Biobank.
Pan C et al.·Prog Neuropsychopharmacol Biol Psychiatry
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Male Infertility

Efficacy Study of a Food Supplement With Myo-inositol, N-Acetyl-Cystein, Zinc and Vitamins on Sperm DNA Fragmentation

RECRUITING
NCT04959864Phase NAGYNOVStarted 2021-07-07
Isitol®Placebo

External Resources

Links to major genomics databases and tools