DNAH5 is a protein-coding gene.1 It provides the instructions for synthesizing a protein that belongs to a microtubule-associated protein complex made of heavy, light and intermediate chains.2DNAH5 is responsible for making the heavy chain 5, found within the outer dynein arms of cilia.1 It will function as a force generating protein by using ATP, producing the power stroke for cilia.3
During early development, the cilia found on the primitive node will beat in a directional pattern, sending signaling molecules to the left, this process will begin to establish the internal left-right asymmetry.3
Mutations in DNAH5 are linked to primary ciliary dyskinesia, an autosomal recessive disorder.4 This disorder is characterized by recurrent respiratory infections, infertility, and abnormal organ placement.1 Non-functional DNAH5 proteins have been identified in individuals with primary ciliary dyskinesia and randomized left-right asymmetry.4
Mutations in DNAH5 are a common cause of primary ciliary dyskinesia,[8] a rare autosomal recessive disorder that can lead to chronic respiratory infections, reduced fertility, and abnormal placement of internal organs6,8. DNAH5 encodes a heavy chain protein found in the outer dynein arms of motile cilia, where it helps generate the force needed for normal ciliary beating6. When DNAH5 is mutated, cilia cannot beat properly, and this can disrupt the movement of fluid and signaling molecules during early embryonic development. Because of this disruption, left-right patterning may fail6., leading to situs inversus totalis, heterotaxy, or congenital heart defects7.
Studies in patients with DNAH5 mutations have also shown that the protein may be absent from the ciliary axoneme or incorrectly localized,[9] which helps explain the loss of ciliary function. In mouse knockout models, disruption of DNAH5 produces similar laterality defects6, confirming that the gene is important for normal embryonic left-right asymmetry. These knockout studies also support the idea that defective nodal cilia movement is a major cause of the abnormal organ placement seen in affected humans9.
↑"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑Chapelin C, Duriez B, Magnino F, Goossens M, Escudier E, Amselem S (Sep 1997). "Isolation of several human axonemal dynein heavy chain genes: genomic structure of the catalytic site, phylogenetic analysis and chromosomal assignment". FEBS Lett. 412 (2): 325–30. doi:10.1016/S0014-5793(97)00800-4. PMID9256245. S2CID23935907.
↑Olbrich H, Haffner K, Kispert A, Volkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, Zariwala M, Noone PG, Knowles M, Mitchison HM, Meeks M, Chung EM, Hildebrandt F, Sudbrak R, Omran H (Jan 2002). "Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry". Nat Genet. 30 (2): 143–4. doi:10.1038/ng817. PMID11788826. S2CID1603234.
Djakow J, Svobodová T, Hrach K, Uhlík J, Cinek O, Pohunek P. Effectiveness of sequencing selected exons of DNAH5 and DNAI1 in diagnosis of primary ciliary dyskinesia. Pediatric Pulmonology. 2012;47(9):864-875. doi:10.1002/ppul.22520.
Andjelkovic M, Minic P, Vreca M, et al. Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants. PLOS ONE. 2018;13(10). doi:10.1371/journal.pone.0205422.
Xu X, Gong P, Wen J. Clinical and genetic analysis of a family with Kartagener syndrome caused by novel DNAH5 mutations. Journal of Assisted Reproduction and Genetics. 2016;34(2):275-281. doi:10.1007/s10815-016-0849-3.
Jouannet P, Escaller D, Serres C, David G (1983). "Motility of human sperm without outer dynein arms". J. Submicrosc. Cytol. 15 (1): 67–71. PMID6221120.
Vaughan KT, Mikami A, Paschal BM, etal. (1997). "Multiple mouse chromosomal loci for dynein-based motility". Genomics. 36 (1): 29–38. doi:10.1006/geno.1996.0422. PMID8812413.
Neesen J, Koehler MR, Kirschner R, etal. (1997). "Identification of dynein heavy chain genes expressed in human and mouse testis: chromosomal localization of an axonemal dynein gene". Gene. 200 (1–2): 193–202. doi:10.1016/S0378-1119(97)00417-4. PMID9373155.
Omran H, Häffner K, Völkel A, etal. (2000). "Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene". Am. J. Respir. Cell Mol. Biol. 23 (5): 696–702. doi:10.1165/ajrcmb.23.5.4257. PMID11062149.
