DNAH7 (dynein axonemal heavy chain 7, also hDHC2) is a 4024-residue heavy chain of single-headed inner dynein arms (IDAs) in motile cilia and sperm flagella. Like other axonemal dynein heavy chains it has an N-terminal stem (tail) that docks it into the axoneme, and a C-terminal motor head of six AAA+ modules with a coiled-coil stalk that ends in a microtubule-binding domain; ATP hydrolysis in the head drives minus-end-directed force on the adjacent doublet microtubule. Cryo-EM of human respiratory doublet microtubules assigns DNAH7 as the heavy chain of two IDA species, IDAb and IDAe, within each 96-nm axonemal repeat. DNAH7 is induced during differentiation of airway multiciliated cells and lies along the length of respiratory cilia and the sperm flagellum. Its axonemal assembly depends on the CCDC39/CCDC40 molecular ruler, and in sperm it is depleted when radial spoke 1 (IQUB) is lost. Biallelic loss-of-function variants cause male infertility with asthenozoospermia or multiple morphological abnormalities of the sperm flagella (MMAF): patient sperm lose inner dynein arms, other IDA heavy chains (DNAH3, DNAH6) are reduced while outer-arm proteins are retained, and mitochondrial sheath defects can occur. UniProt records the disorder as primary ciliary dyskinesia 50 (CILD50), with sinopulmonary symptoms reported in addition to infertility. Fertility can be achieved by ICSI.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003341 cilium movement | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of cilium movement. DNAH7 is an inner dynein arm heavy chain of respiratory cilia and sperm flagella, and its loss impairs flagellar beating. Reason: Consistent with DNAH7 being a force-generating component of the axonemal inner arms and with the human genetics. Supporting Evidence: PMID:37258679 IDAb and IDAe are both DNAH7 |
| GO:0003341 cilium movement | IMP PMID:11877439 Identification of dynein heavy chain 7 as an inner arm compo... | ACCEPT | Summary: Zhang et al. (2002) identified DNAH7 by mass spectrometry as a protein missing from cilia of a PCD patient whose cilia lacked inner dynein arms. The patient's cells still synthesised DNAH7, so the primary genetic lesion was probably not in DNAH7 itself. Reason: The original paper is not a DNAH7 loss-of-function study in the strict sense (DNAH7 was "synthesized but not assembled"), and its full text is not cached. However, the acts_upstream_of_or_within qualifier is appropriate, and later DNAH7 loss-of-function patients (IDA loss, impaired flagellar motility, CILD50) independently support DNAH7 acting in cilium movement. Deferring to the curator. Supporting Evidence: PMID:11877439 In cilia from PCD cells, DNAH7 was undetectable, whereas intracellular DNAH7 was clearly present. PMID:34476482 The spermatozoa from the patients with DNAH7 bi-allelic mutations showed specific losses in the inner dynein arms. |
| GO:0003777 microtubule motor activity | IC PMID:11877439 Identification of dynein heavy chain 7 as an inner arm compo... | TOO GENERAL | Summary: Inferred by curator from the inner dynein arm localization. DNAH7 has a complete dynein motor head (AAA1-AAA6, stalk), so microtubule motor activity is expected. Reason: True but uninformative: minus-end-directed microtubule motor activity (GO:0008569), ACCEPTed in this review by IBA and IEA, is_a microtubule motor activity and entails it. GO:0008569 is the core function. No direct motility assay exists for human DNAH7. Supporting Evidence: PMID:11877439 These studies identify DNAH7 as an inner arm component of human cilia |
| GO:0003777 microtubule motor activity | NAS PMID:9373155 Identification of dynein heavy chain genes expressed in huma... | TOO GENERAL | Summary: Non-traceable author statement from the 1997 cloning of testis dynein heavy chain fragments (HDHC7, an inner arm dynein). Reason: True but uninformative: minus-end-directed microtubule motor activity (GO:0008569), ACCEPTed in this review, is_a microtubule motor activity and entails it. The paper only cloned the ATP-binding region. Same action as the IC row for this term. Supporting Evidence: PMID:9373155 Two of these clones, gHDHC7 and gMDHC7, are homologous genes encoding axonemal inner arm dyneins. |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro EF-hand domain signature (IPR002048) mapped to calcium ion binding. The UniProt entry carries the IPR002048 cross-reference, but has no EF-hand domain feature and no calcium-binding site annotated in DNAH7. Reason: There is no experimental evidence that the DNAH7 heavy chain binds calcium. Calcium regulation of the centrin-containing single-headed IDAs is attributed to their centrin light chain, and IDAb/IDAe (DNAH7) resemble IDAg in this respect. A lone InterPro signature that UniProt does not place as an EF-hand feature is a weak basis for an MF annotation of a 4000-residue motor. Supporting Evidence: PMID:37258679 the motor domains of IDAb and IDAe are copies of IDAg, the other centrin-containing IDA |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding from InterPro. UniProt annotates P-loop ATP-binding sites in the stem and in AAA1-AAA4. Reason: Structurally sound but uninformative; ATP binding is part of the motor activity captured by minus-end-directed microtubule motor activity. Supporting Evidence: file:human/DNAH7/DNAH7-uniprot.txt FT BINDING 1328..1335 |
| GO:0005858 axonemal dynein complex | NAS PMID:9373155 Identification of dynein heavy chain genes expressed in huma... | MODIFY | Summary: Author statement that the testis clone encodes an axonemal inner arm dynein. Reason: Correct but less specific than inner dynein arm, which is supported by IMP and by cryo-EM assignment of DNAH7 to IDAb and IDAe. Proposed replacements: inner dynein arm Supporting Evidence: PMID:37258679 IDAb and IDAe are both DNAH7 |
| GO:0005929 cilium | IDA PMID:11877439 Identification of dynein heavy chain 7 as an inner arm compo... | TOO GENERAL | Summary: Immunohistochemistry showed DNAH7 in normal human airway cilia. Reason: Direct localization and true, but uninformative: 9+2 motile cilium (GO:0097729, is_a cilium) and axoneme (GO:0005930, part_of cilium), both ACCEPTed in this review, entail it. Supporting Evidence: PMID:11877439 immunohistochemistry demonstrated the presence of DNAH7 in normal cilia |
| GO:0005930 axoneme | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (cilium axoneme). Reason: DNAH7 is an axonemal inner arm subunit, localized along the entire length of respiratory ciliary axonemes. Supporting Evidence: PMID:39056782 In healthy control subjects, DNAH7 is localized throughout the entire length of ciliary axonemes |
| GO:0007018 microtubule-based movement | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro dynein heavy chain mapping to microtubule-based movement. Reason: DNAH7 retains a complete motor domain and is a force-generating IDA heavy chain, so the term is true but uninformative: cilium movement involved in cell motility (GO:0060294) and cilium movement (GO:0003341), both ACCEPTed in this review, are descendants of microtubule-based movement and entail it. |
| GO:0008569 minus-end-directed microtubule motor activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of minus-end-directed microtubule motor activity from a deep dynein heavy chain node. Reason: DNAH7 is within the clade of conventional, full-length dynein heavy chains (complete AAA1-AAA6 ring, stalk and microtubule-binding region), with no evidence of loss of motor function. Axonemal dyneins drive sliding of doublets toward the minus end; this is the core molecular function. Supporting Evidence: file:human/DNAH7/DNAH7-uniprot.txt Produces force towards the minus ends of microtubules. |
| GO:0008569 minus-end-directed microtubule motor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping of minus-end-directed microtubule motor activity. Reason: Consistent with the IBA and with the domain architecture of DNAH7. |
| GO:0030286 dynein complex | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to the general dynein complex term. Reason: Correct but too general; DNAH7 is specifically an inner dynein arm heavy chain. Proposed replacements: inner dynein arm Supporting Evidence: PMID:37258679 IDAb and IDAe are both DNAH7 |
| GO:0031514 motile cilium | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location (flagellum) mapped to motile cilium. Reason: DNAH7 is present in both respiratory motile cilia and the sperm flagellum. |
| GO:0036126 sperm flagellum | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of sperm flagellum localization. Reason: Immunofluorescence studies of patient and control sperm show DNAH7 in the flagellum, reduced in carriers of loss-of-function variants. Supporting Evidence: PMID:40810911 immunofluorescent staining revealed a marked reduction of DNAH7 and other IDA-associated proteins, such as DNAH3 and DNAH6, in the patients' spermatozoa |
| GO:0036156 inner dynein arm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of inner dynein arm membership; DNAH7 (Q8WXX0) itself is the experimental seed of the IBD at PTN008503981. Reason: Core cellular component. DNAH7 is the heavy chain of IDAb and IDAe by cryo-EM; its presence in the IBD WITH/FROM reflects the experimental grounding on the target itself. Supporting Evidence: PMID:37258679 IDAb and IDAe are both DNAH7 |
| GO:0036156 inner dynein arm | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of inner dynein arm membership. Reason: Consistent with experimental and structural evidence. |
| GO:0036156 inner dynein arm | IMP PMID:11877439 Identification of dynein heavy chain 7 as an inner arm compo... | ACCEPT | Summary: DNAH7 was identified as a protein missing from PCD cilia that lacked inner dynein arms, and is described by the authors as an inner arm component. Reason: The inner dynein arm assignment has been confirmed independently by cryo-EM of human respiratory axonemes, which places DNAH7 in IDAb and IDAe. Supporting Evidence: PMID:11877439 These studies identify DNAH7 as an inner arm component of human cilia PMID:37258679 IDAb and IDAe are both DNAH7 |
| GO:0036159 inner dynein arm assembly | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBD at PTN008951089, seeded by DNAH3, DNAH7 and a mouse IDA heavy chain. Reason: DNAH7 participates in IDA assembly as a structural heavy chain: loss of DNAH7 removes inner arms from sperm and reduces the other IDA heavy chains DNAH3 and DNAH6, while outer arm proteins remain. DNAH7 appearing among the IBD sources marks experimental grounding on the target. Supporting Evidence: PMID:40810911 our findings confirmed that DNAH7 variants may contribute to asthenozoospermia by affecting flagellar IDA assembly |
| GO:0036159 inner dynein arm assembly | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of inner dynein arm assembly. Reason: Consistent with the IBA and with patient sperm data. |
| GO:0036159 inner dynein arm assembly | IMP PMID:11877439 Identification of dynein heavy chain 7 as an inner arm compo... | ACCEPT | Summary: acts_upstream_of_or_within inner dynein arm assembly, from the PCD case in which DNAH7 was not assembled into cilia lacking inner arms. Reason: The 2002 case does not establish that DNAH7 loss causes IDA loss, but subsequent DNAH7 loss-of-function patients do show specific IDA loss in sperm, so the annotation is correct for the gene; the acts_upstream_of_or_within qualifier is appropriately cautious. Supporting Evidence: PMID:35543642 The axoneme structure of the sperm from a DNAH7-deficient patient revealed the loss of inner dynein arms. |
| GO:0045505 dynein intermediate chain binding | IBA GO_REF:0000033 | UNDECIDED | Summary: Family-level PAINT inference of dynein intermediate chain binding. Reason: Single-headed inner arm species such as IDAb and IDAe are not known to contain dynein intermediate chains (these belong to the outer arm and the two-headed IDAf/I1 complex), and no DNAH7-intermediate chain interaction has been reported. The inference probably reflects cytoplasmic and outer-arm dynein biology at a deep node, but without direct data it is left UNDECIDED rather than refuted. Propagation Review Root cause: UNRESOLVED Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000743491 UNRESOLVED Deep dynein heavy chain node spanning cytoplasmic and axonemal dyneins; the dynein intermediate chain binding IBD is seeded only by a Dictyostelium cytoplasmic dynein heavy chain. dictyBase:DDB_G0276355 SUPPORTS SOURCE BUT NOT TARGET Cytoplasmic dynein heavy chain; intermediate chain binding is well established there but single-headed axonemal inner arms are not known to carry intermediate chains. |
| GO:0045505 dynein intermediate chain binding | IEA GO_REF:0000002 | UNDECIDED | Summary: InterPro family mapping of dynein intermediate chain binding. Reason: Same considerations as the IBA; no DNAH7-specific data. |
| GO:0051959 dynein light intermediate chain binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Family-level PAINT inference of dynein light intermediate chain binding. Reason: Plausible: DNAH7 is described among the DNALI1-associated IDA heavy chains whose axonemal assembly fails together with DNALI1 in ruler defects, but direct binding of DNAH7 to DNALI1 has not been shown. Supporting Evidence: PMID:39056782 we investigated the localization of the DNALI1-associated dynein heavy chains DNAH1 and DNAH7 and the CETN2-associated heavy chain DNAH6 |
| GO:0051959 dynein light intermediate chain binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro family mapping of dynein light intermediate chain binding. Reason: Same considerations as the IBA. |
| GO:0060285 cilium-dependent cell motility | NAS PMID:9373155 Identification of dynein heavy chain genes expressed in huma... | MODIFY | Summary: Author statement from the testis cloning paper that axonemal dyneins are essential for motility of cilia and flagella. Reason: cilium-dependent cell motility is correct only for the sperm flagellum; the more specific flagellated sperm motility is supported by DNAH7 loss-of-function patients with asthenozoospermia. Proposed replacements: flagellated sperm motility Supporting Evidence: PMID:34476482 bi-allelic mutations in DNAH7 may impair the integrality of axoneme structure, affect sperm motility, and cause asthenozoospermia in humans |
| GO:0060294 cilium movement involved in cell motility | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of cilium movement involved in cell motility. Reason: DNAH7 drives sperm flagellar beating; loss-of-function patients have asthenozoospermia. Supporting Evidence: PMID:40810911 loss-of-function variants in DNAH7 were identified in two unrelated infertile men with asthenozoospermia |
| GO:0097225 sperm midpiece | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence localization to the sperm midpiece. Reason: The midpiece is part of the sperm flagellum, which contains the axoneme throughout; DNAH7 is expected along the whole flagellum, so this is a partial view of its location rather than a midpiece-specific function. |
| GO:0097227 sperm annulus | IDA GO_REF:0000052 | UNDECIDED | Summary: Human Protein Atlas immunofluorescence localization to the sperm annulus. Reason: The annulus is a septin ring at the midpiece-principal piece junction, not an axonemal structure. An axonemal inner arm heavy chain would be expected along the full flagellum, so this antibody signal may reflect staining at the junction rather than annulus membership. The HPA image was not inspected, so the annotation is neither accepted nor removed. |
| GO:0097729 9+2 motile cilium | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of 9+2 motile cilium localization. Reason: DNAH7 is an axonemal component of 9+2 respiratory cilia and sperm flagella. Supporting Evidence: PMID:39056782 In healthy control subjects, DNAH7 is localized throughout the entire length of ciliary axonemes |
| GO:0120316 sperm flagellum assembly | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of sperm flagellum assembly. Reason: DNAH7 loss causes MMAF and IDA loss in sperm, showing it is needed for a correctly assembled flagellum. Supporting Evidence: PMID:35543642 DNAH7 disruption in humans results in male infertility, which was characterised by multiple morphological abnormalities of sperm flagella |
Loading supporting content…
Download this section (compressed HTML)Q: Do DNAH7 loss-of-function patients have clinically significant respiratory disease? UniProt files the disorder as CILD50, but most reported cases were ascertained through infertility clinics; respiratory ciliary beat and nasal NO data in DNAH7-null individuals would clarify whether IDAb/e loss alone causes PCD.
Q: Do IDAb and IDAe (both DNAH7) differ in light-chain composition (centrin versus DNALI1/p28) in human axonemes, and does this explain the family-level light intermediate chain and intermediate chain binding annotations?
Q: Mouse has three Dnah7 paralogs (Dnah7a, Dnah7b, Dnah7c); is there redundancy that would mask a single-gene knockout phenotype, and which paralog corresponds functionally to human DNAH7?
Experiment: High-speed videomicroscopy and cryo-ET of airway cilia from DNAH7-null individuals to test whether loss of IDAb/e alters ciliary waveform.
Type: ciliary beat analysis and cryo-electron tomography
Experiment: Recombinant DNAH7 motor domain in vitro motility and microtubule gliding assays to measure velocity and directionality.
Type: in vitro motility assay
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)