CCDC39

Summary: CCDC39-dependent motile-cilium function contributes to normal heart looping during left-right patterning.

Reason: The cited clinical paper remains abstract-only, so its detailed cardiac phenotype mapping was not independently inspected. Separately, PMID:21131972 directly tests zebrafish ccdc39 depletion with two morpholinos and rescues the laterality/heart-looping phenotype using human CCDC39 mRNA. This supports a conserved contribution through motile cilia, without assigning CCDC39 a direct cardiac morphogenetic or contractile mechanism. Retain this developmental consequence as non-core rather than infer that an inaccessible clinical table is erroneous.

Summary: The InterPro-derived cilium-movement assertion agrees with direct human loss-of-function evidence.

Reason: The preserved InterPro family mapping is consistent with human respiratory cilia becoming immotile or stiff and ineffective when CCDC39 is deficient. Human structural data identify the axonemal scaffold whose disruption explains this motility defect. CCDC39 contributes the organized apparatus used for movement; it is not itself the dynein motor.

Summary: The heterotaxy study includes CCDC39-mutant PCD controls with abnormal ciliary movement.

Reason: Although the canonical cache is abstract-only, the authenticated, separately retained XML body was read. It identifies PCD controls 9028 and 9098 homozygous for CCDC39 1972delA, links 9028 to the abnormal-motion video and characteristic ultrastructure, and describes blinded video assessment. Thus the CCDC39 assertion is not rejected because the title foregrounds heterotaxy. Independent human CCDC39 studies corroborate the same core role; the canonical cache remains unchanged and no artifact-only quotation is used.

Summary: CCDC39 loss alters measured beat frequency as well as beat pattern.

Reason: The primary human study measures nasal cilia at defined temperatures and reports lower mean beat frequency in CCDC39 patients, with many cilia immotile and a wide frequency range among those still moving. This supports an effect on the rate of ciliary beating through axonemal organization. It does not establish an acute frequency-sensing switch or an independently catalytic regulator, so retain the regulatory phenotype outside the structural core.

Summary: The inferred extracellular location conflates extracellular fluid movement with the location of the axonemal scaffold.

Reason: GO_REF:0000108 propagates from the left-right epithelial-cilium movement process. Official ontology links lead through epithelial extracellular-fluid movement and extracellular transport to extracellular region. That process geography does not place the protein outside the plasma membrane: human immunofluorescence and cryo-EM locate CCDC39 in the membrane-enclosed axoneme, where it organizes the 96-nm repeat. The electronic route supplies no independent secretion or extracellular-matrix evidence. Remove this particular location inference on that mechanistic mismatch, without asserting that every conceivable extracellular release of CCDC39 has been excluded.

Summary: A cytoplasmic CCDC39 pool is observed, but the specific mouse-derived cytosol assertion is unresolved.

Reason: The source is an Ensembl Compara transfer from the preserved mouse identifiers. Its underlying localization experiment was not recovered. Human CCDC39 accumulates at the apical cytoplasm/ciliary base in CCDC40-deficient cells, but that imaging does not distinguish soluble cytosol from an associated assembly or trafficking compartment and is not a wild-type mouse cytosol assay. Retain uncertainty rather than convert cytoplasm into a more specific soluble location or infer absence from the axonemal role.

Summary: CCDC39 is a ciliary protein, including in respiratory cilia examined in the GAS8 study.

Reason: The independently verified abstract explicitly reports CCDC39/CCDC40 immunofluorescence in human respiratory cilia and preservation in GAS8-deficient cells. Full Methods for this particular paper were inaccessible, but the cellular location is independently demonstrated in the fully accessed human CCDC39 and CCDC40 studies and the human structural study. Accept the correct broad location with curator deference; do not imply that the GAS8 paper was read in full.

Summary: The PAINT axoneme inference is supported by direct human localization and conserved structural function.

Reason: This IBA represents a curated ancestral-state judgment, not a vote based on donor count. Human Q9UFE4 appearing among its descendant evidence is expected and is not circular. Human immunofluorescence and the 96-nm axonemal structural model independently support localization; no target-specific loss of this conserved property is evident. The exact PAINT tree/node placement was not reconstructed.

Summary: The original human study directly localizes CCDC39 to respiratory ciliary axonemes.

Reason: Control respiratory cells contain CCDC39 along the axoneme, whereas CCDC39-deficient patient cells lose the signal; the study also checks the corresponding protein band. These target-specific controls directly support the axonemal location and complement its structural role.

Summary: The CCDC40 study independently tests axonemal localization of CCDC39.

Reason: Human control and CCDC40-mutant respiratory cells were compared using CCDC39 and tubulin immunofluorescence, with omission-of-primary-antibody controls in the Methods. CCDC39 is lost from the mutant cilium and enriched at the apical base, showing CCDC40-dependent targeting rather than a study restricted to an unrelated paralog.

Summary: CCDC39 localization is directly assessed in the human GAS8 diagnostic study.

Reason: The selected primary Methods specify anti-CCDC39 immunofluorescence on nasal respiratory epithelial cells and the Results distinguish GAS8-deficient cases with preserved CCDC39 localization from CCDC39/CCDC40 defects. This is target-specific localization evidence even though GAS8 is the main gene in the title; independent original localization and structural data agree.

Summary: The combined electronic axoneme annotation agrees with direct localization.

Reason: The source combines the preserved InterPro and UniProt subcellular-location evidence. Human CCDC39 localization and structural placement in the 96-nm axonemal repeat support this location independently. Combining the electronic methods does not turn them into separate experiments, but their conclusion is sound.

Summary: The literature-supported axoneme location is consistent with target-specific human evidence.

Reason: The GAS8 paper explicitly discusses CCDC39/CCDC40-dependent axonemal organization and uses CCDC39 immunofluorescence in human respiratory cells. Its TAS location is consistent with the direct CCDC39 localization studies and the later human structural model. Preserve this source assertion alongside the independent IDA rows.

Summary: Human CCDC39 deficiency impairs sperm motility.

Reason: The source records sperm dysmotility in three CCDC39 patients, while noting that those data are not shown. The original CCDC39 study independently reports oligoasthenospermia in affected men. These observations support the existing sperm-cell motility process as a tissue-specific use of the axonemal scaffold; no detailed sperm waveform, flagellar substructure or fertility mechanism beyond those observations is claimed.

Summary: A specific lung-development role cannot be separated from pulmonary consequences of ciliary dysfunction in the available source.

Reason: The cited primary paper is a human clinical/genetic study, but its full body and detailed phenotype tables were inaccessible. The available abstract establishes CCDC39-associated PCD, airway disease and ciliary structural defects; these do not by themselves distinguish lung morphogenesis from impaired mucociliary clearance or laterality phenotypes. Preserve the IMP assertion pending the actual developmental evidence, without treating the abstract as proof that curators misattributed it.

Summary: CCDC39 is a component of motile respiratory cilia.

Reason: Human respiratory epithelial cilia are the structures examined in the cited GAS8 diagnostic study and in the original CCDC39 localization work. The later human axonemal model places CCDC39 in the motile-cilium 96-nm scaffold. This supports the broader motile-cilium compartment without introducing a second unrelated location.

Summary: The pancreas-specific laterality assertion requires the unavailable detailed clinical evidence.

Reason: CCDC39-dependent motile cilia have a well-supported role in organismal left-right patterning. However, the abstract-only cited study does not expose the pancreas-specific observations or distinguish organ position from the developmental process asserted here. Its detailed clinical table was not recovered; retain uncertainty rather than deny the experimental annotation or assign a direct pancreatic mechanism.

Summary: The PAINT inner-dynein-arm assembly assertion agrees with target-specific human structural defects.

Reason: The IBA is a curated ancestral functional inference at the preserved PTN node. Human CCDC39 is legitimate descendant experimental evidence within that inference, not a circular source. Human deficient axonemes lose inner dynein arms while outer arms remain largely intact, and the structural model identifies the associated 96-nm scaffold. These findings support conserved participation in assembly without requiring CCDC39 to be a dynein motor.

Summary: The InterPro-derived inner-dynein-arm assembly function is experimentally corroborated.

Reason: The electronic family mapping agrees with human patient ultrastructure, DNALI1 localization and the loss of organized 96-nm axonemal structures. This is a specific scaffold contribution to arranging inner dynein arms, not an extrapolated ATPase activity or a claim that outer dynein-arm assembly is also lost.

Summary: Human CCDC39-deficient axonemes lack inner dynein arms.

Reason: The source directly examines at least 30 ciliary cross-sections per patient and reports loss of inner dynein arms in CCDC39 cases while outer arms remain apparent. The genetic loss-of-function and structural findings support a role in assembling or maintaining the organized inner-arm apparatus. Later human cryo-EM identifies the disrupted repeat scaffold, strengthening participation beyond an unexplained phenotype.

Summary: CCDC39 participates in organizing the internal structure of motile cilia.

Reason: The source shows that cilia form but their inner dynein arms and microtubule organization are disrupted. Assembly includes arranging ciliary components into the functional structure; it does not require complete loss of cilium production when the scaffold is missing. The human 96-nm structural-repeat defect provides a concrete basis for this broader assembly assertion.

Summary: The cilium-organization inference is supported by CCDC39-dependent axonemal architecture.

Reason: The source infers cilium organization from protein localization to the cilium. Independently, human CCDC39 loss disrupts inner-arm/DRC arrangement and the recognizable 96-nm repeat, directly connecting the protein to organization of the ciliary apparatus. Ciliary entry and correct periodic docking are distinguished: radial spokes can still enter deficient cilia but bind sporadically.

Summary: The conserved cell-motility assertion is compatible with the sperm phenotype, rather than inferred solely from airway fluid movement.

Reason: GO:0060285 concerns movement of a cell by its cilium or flagellum; it is not synonymous with respiratory fluid transport. Human CCDC39-associated sperm dysmotility and oligoasthenospermia provide the relevant whole-cell context. Retain the PAINT judgment with that boundary and no criticism based on its own-target descendant evidence; the exact ancestral reconstruction was not independently repeated.

Summary: The original CCDC39 paper includes a human sperm-motility phenotype relevant to movement of cells.

Reason: The study reports oligoasthenospermia in four affected males, separately from its respiratory-cilium and zebrafish laterality experiments. This supports retaining the broad cilium-dependent cell-motility assertion through the flagellated sperm context; epithelial fluid movement alone would not suffice. Detailed sperm kinematics were not independently available.

Summary: The PAINT left-right ciliary-flow function is consistent with the conserved laterality phenotype.

Reason: Human laterality defects and zebrafish ccdc39 depletion/rescue support a conserved role in the ciliary machinery required for left-right patterning. The source reflects curated ancestral inference, not a claim that the human protein was individually assayed in every listed organism. Keep this developmental context outside the principal axonemal assembly core, without extending it into unverified organ-specific mechanisms.

Summary: CCDC39-dependent ciliary function contributes to embryonic left-right patterning.

Reason: The original study combines human laterality phenotypes with two zebrafish morpholinos, altered southpaw expression and heart looping, and rescue with human CCDC39 mRNA. This supports the existing left-right ciliary-flow process. The inspected experiments do not constitute direct imaging of human embryonic nodal flow; the inference is interpreted within that conserved developmental context.

Summary: CCDC39 is required for proper axonemal localization of selected ciliary components.

Reason: The cited primary Results explicitly describe absent axonemal GAS8 in human CCDC39/CCDC40 deficiency, corroborating the original human study. This supports protein localization to cilium in the sense of assembling/retaining proteins at their axonemal destination. It does not establish that CCDC39 is an intraflagellar-transport motor or that it controls entry of every ciliary protein; radial-spoke entry can persist despite disordered periodic docking.

Summary: CCDC39 contributes to axonemal dynein-complex assembly, principally the inner-arm apparatus.

Reason: Human CCDC39 deficiency removes DNALI1-containing inner dynein arms and disrupts the DRC-associated architecture, while tested outer-arm markers and the outer-arm repeat remain preserved. The broad source process is therefore sound but should not be read as evidence that CCDC39 assembles all dynein classes. The more specific inner-arm process is used in the structural core summary.

Summary: The digestive-tract-specific laterality assertion remains unverified at the detailed source level.

Reason: The available primary abstract does not expose the organ-specific clinical observations or developmental interpretation behind this IMP row. General laterality evidence establishes a plausible ciliary connection but does not resolve this exact digestive-tract process. Retain the machine assertion and its uncertainty pending the full source; no incorrect-gene or incorrect-organism claim is made.

Summary: The liver-specific laterality assertion remains unresolved from the accessible clinical source.

Reason: The cited paper was verified as the intended CCDC39/CCDC40 clinical study, but the full body and organ-specific tables were unavailable. A general situs phenotype is compatible with CCDC39-dependent motile-cilium function; it does not independently establish the precise liver-development process or a direct hepatic role. Preserve uncertainty rather than remove an experimental assertion from abstract silence.

Summary: CCDC39 contributes the structural scaffold of the human axonemal 96-nm repeat.

Reason: Human respiratory-axoneme cryo-EM places the CCDC39–CCDC40 coiled coil in the wild-type 96-nm structural repeat and compares sequence-verified CCDC39 loss-of-function axonemes with particle-number/resolution-matched controls. The mutant loses the recognizable 96-nm repeat while the outer-arm 24-nm repeat is preserved. This combines direct structural placement with a selective structural perturbation, supporting contribution to cytoskeletal integrity rather than inferring molecular activity from disease necessity alone. The specific tether contacts illustrated for Chlamydomonas are not asserted as independently resolved human interactions. GO:0005200 is a structural molecular function, not a new developmental process; no equivalent MF exists among the 30 source assertions. Complete current same-role comparator datasets were inaccessible, so their absence is not claimed or used as evidence of a curation gap.