FAM149B1 intake notes

2026-10-25: Completed authorized private mechanical bootstrap from accepted identity/ownership preflight. Six raw/TSV/PENDING contexts, three seed references and two literal source products remain exact. See FAM149B1-source-guide.md for source, product and access boundaries and the genuine provider failure.

No original Methods/Results, supplement or figure pixels were read; no annotation decisions, standalone biological description, core functions, new quotations or NEW rows were authored. Displayed and shorter splice products were reconstructed mechanically, with external RefSeq/Ensembl models kept separate. Actual PAINT target mapping is preserved for later scientific review, including valid self-WITH descendant evidence.

The setup stopped before source fetching when it encountered a private genuine PMID10231032 cache absent from fixed main. That cache was subsequently qualified against the accepted EXOC6B intake and original successful normal fetch, then reused byte-exact. The failed setup and all provider failures remain saved; no immutable cache was overwritten or restored.

Historical accepted direct-lane appendix

Direct evidence review — 2026-10-25

These are agent-authored review notes. The earlier paragraph records the intake checkpoint, before original reading. This direct lane reviews only indices 0, 3 and 5: one ACCEPT, one MODIFY and one KEEP_AS_NON_CORE. The other three database annotations remain PENDING. The source records, INITIALIZED status, seed description and two natural product records are preserved; core synthesis is a later step.

Human FAM149B1-mutant fibroblasts in PMID:30905400(https://doi.org/10.1016/j.ajhg.2019.02.018) retain a normal frequency of ciliation but have longer cilia with bulbous, IFT88/IFT46-rich tips. IFT122 distribution is relatively preserved. The independently generated human RPE1 knockout and rescue in PMID:35609210(https://doi.org/10.1091/mbc.E22-03-0089) corroborate control of cilium length and IFT88 distribution. Cilium organization captures the measured architecture more directly than an assertion confined to initial assembly. Protein localization to cilium is retained because its current definition includes maintenance of protein position within the organelle. The N-terminal 1–179 fragment rescues IFT88 tip accumulation without correcting length, separating these outputs rather than proving a general transport motor mechanism.

The 2019 GFP-tagged FAM149B1/MYC-DDK-TBC1D32 co-IP and the 2022 tagged association/domain-mapping experiments support cellular association. IgG and EGFP-only controls were inspected. They do not identify a purified binary interface or a native stoichiometric complex. Supported generic binding is retained as non-core under the standing campaign exception. The current adaptor and cargo-adaptor definitions do not justify assigning a bridging or motor-cargo function from these experiments. The 2022 cyclin-like CCRK-regulator proposal is a hypothesis; no corresponding FAM149B1 kinase-regulation assay was established.

Clinical variants and engineered constructs remain distinct from natural products. The 2019 clinical analysis uses NM_173348.1/NP_775483.1, but the complete co-IP insert sequence is not reported. The 2022 methods specify human NM_173348.2 and full-length 582-residue, 1–179 and 180–582 constructs. The two fragments are engineered, and these results do not show equivalence of the natural 528-residue product. The inability to distinctly localize FAM149B1 itself to cilia in the 2022 study is recorded separately from its effects on ciliary protein distribution; it neither proves absence in every context nor supplies direct human ciliary localization evidence.

Both selected publication caches report full text available, and both reference flags follow that immutable metadata. Actual access and reading are recorded separately. The genuine 2019 PII-specific publisher PDF contains the main article and supplement; Figure 3, Figure 5 and Supplementary Figure S1 pixels were viewed. Generic BioStudies mmc downloads were unrelated articles and excluded. The 2022 official main text, target-specific methods/results, supplemental captions and construct tables were read; Supplementary Figures S2/S3 pixels were viewed, but main Figure 6/7 pixels and supplementary videos were not. The added PMID:35609210 normal record was genuinely fetched in an isolated copy with all prior files preserved. No publication quotations or NEW annotations were added.

Historical accepted database-lane appendix

2026-10-25 database review checkpoint

The preceding intake paragraph records the earlier acquisition-only scope. This database review subsequently read selected actual 2019 and 2022 original Methods/Results and the figures specified in FAM149B1-source-guide.md. It reviewed indices 1, 2 and 4 only: one UNDECIDED ciliary-location inference, one MODIFY from cilium assembly to its cilium-organization parent, and one ACCEPT for protein localization within cilia. The other three direct contexts remain PENDING at this lane checkpoint; INITIALIZED is unchanged.

The v19 tree and actual IBD file verify human PTN002528684 below PTN002842395 for both inherited processes. Target self-WITH is legitimate experimental grounding, not circularity. Assembly generalization concerns the observed length and component-arrangement endpoint, not an ancestry failure. The cilium-location uncertainty preserves UniProt's positive inferred location and the later unsuccessful distinct-localization observation without treating the latter as universal absence.

Both original publication caches have full_text_available=true. Their author full_text_unavailable flags therefore remain false, while the guide separately lists bounded reading and figure inspection. PMID:35609210 is the genuine additive normal already obtained by the direct reviewer; it is reused byte-exact, with no new publication fetch, source-cache rewrite or quotation. The 582- and 528-residue natural products remain distinct from the engineered 1–179 and 180–582 constructs.

2026-10-25 integrated synthesis checkpoint

The preceding intake and lane appendices are historical checkpoints. All six contexts are now reviewed: two ACCEPT, two MODIFY to cilium organization, one KEEP_AS_NON_CORE binding context and one UNDECIDED location inference. Each accepted review object is preserved exactly. Both shared publication assessments are losslessly retained with lane labels, including the database Figure 7 pixel read and the direct lane's separate supplementary-image scope. INITIALIZED is retained pending ROOT's canonical validation; this is not a computed completion status.

See FAM149B1-source-guide.md for the combined source record and public locators. One core represents cilium organization and maintenance-inclusive protein localization. Current official is_a and is_a/part_of ancestor responses establish that the two selected process terms are mutually non-ancestral. The core does not assert ciliary target residence, a defined native complex or a molecular activity absent from the experiments. Its BIOLOGY/MF_DARK gap identifies the unresolved molecular link between association, cilium length and protein distribution; it does not erase the positive human process role. Two question/experiment pairs address that mechanism and natural-product-specific localization/function.

The standalone description names Joubert-related ciliopathy and keeps the natural 582/528 products separate from tagged full-length protein, engineered fragments and patient truncations. No NEW annotation, quotation anchor, accepted review edit or normal-source mutation was made. The integration/core author previously authored the database lane and read its listed originals/images; combined scope is attributed to the two accepted lanes, not represented as a new independent whole-gene review.

2026-10-25 assembly-scope feedback revision

The intake, lane and integration paragraphs above are historical checkpoints. The current six reviews are four ACCEPT, one KEEP_AS_NON_CORE and one UNDECIDED; the published DRAFT status is preserved here pending canonical validation. This successor restores both imported GO:0060271 cilium-assembly contexts and the matching core facet. Normal ciliation frequency in patient fibroblasts does not exclude defective assembly/extension, and UniProt VAR_083866 already records that observation. The independent RPE1 knockout/full-length rescue corroborates abnormal length. A hypothetical CCRK-regulatory mechanism does not justify replacing assembly with a regulation term.

PMID:35609210 Figure 7 distinguishes the outputs: intact full-length FAM149B1 restores normal length; neither 1–179 nor 180–582 does so, while 1–179 improves IFT88 distribution. The natural 528-residue product remains untested in these comparisons. The cilium-location inference stays UNDECIDED because unsuccessful distinct localization does not exclude transient, low-abundance or base-associated residence. Controlled cellular coassociation remains non-core binding, without a purified binary-interface or adaptor-function claim.

The active source guide supplies the concise biological reading route and access/construct limits. The PAINT evidence extract reproduces the verified v19 target path and both actual ancestral assertions from preserved public-source captures. Current reference assessments retain both complete labeled lane scopes and unchanged cache flags. This successor reread the specified primary passages and performed saved-source phylogenetic reconstruction; it did not newly inspect figure pixels or entire papers. All original source objects, four reference objects, two natural products, normal caches and prior history records are preserved. No NEW annotation or publication quotation was added.

2026-10-25 — PAINT assessment wording follow-up

The active GO_REF:0000033 assessment now describes retention of cilium assembly at
the imported specificity, matching the two ACCEPT reviews and existing core. This
corrects a stale clause from the earlier assembly-to-organization proposal. All six
review objects, both natural products, reference identities/findings, publication
read scopes and the other reference assessments remain unchanged. Earlier journal
entries retain their historical decisions; they do not replace the active review.
The source guide and existing PAINT evidence
extract
retain the evidence route. No new publication
quotation, annotation or molecular-function assertion is added.