DNAH2

Chr 17AR

dynein axonemal heavy chain 2

Also known as: DNAHC2, DNHD3, SPGF45

NCBI Gene: 146754 ENSG00000183914 UniProt: Q9P225 OMIM: 603333

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).

OMIM ResearchSummary from OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

GOFmechanismARLOEUF 0.561 OMIM phenotype

Clinical Summary— DNAH2

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 152 VUS of 252 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.88Z-score

OE missense 0.90 (0.86–0.93)

2317 obs / 2586.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.41–0.56)

0≤0.351.4

Missense OE?0.90 (0.86–0.93)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 115 / 238.4Missense obs/exp: 2317 / 2586.5Syn Z: -0.29

This gene — mechanism propensity

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

252 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic6

VUS152

Likely Benign19

Benign24

Conflicting2

Pathogenic

Likely Pathogenic

152

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	3	1	0	5
Likely Pathogenic	5	1	0	0	6
VUS	1	151	0	0	152
Likely Benign	0	14	1	4	19
Benign	0	10	5	9	24
Conflicting	—				2
Total	7	179	7	13	208

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap DNAH2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →