Notes for DANRE spns1

• Core function is lysosomal membrane transmembrane transport; the current UniProt record specifies proton-dependent lysophospholipid efflux [file:DANRE/spns1/spns1-uniprot.txt "efflux of lysophospholipids"].
• A proposed new MF term was added because GO:0022857 is too generic for the now-described proton-dependent lysosomal lysophospholipid efflux activity, while no existing specific GO term was found in the local term cache.
• Autophagy and senescence annotations are retained as non-core because they are process consequences of impaired lysosomal transport PMID:24967584.

Falcon deep research enrichment (2026-05)

• Integrated spns1-deep-research-falcon.md (Edison; He 2022 PNAS, Ha 2024 JCI Insight, Chávez 2024 iScience, Coffey 2021 J Dev Biol).
• Substrate refined from generic "lysophospholipids" to the demonstrated zwitterionic substrates LPC and LPE [file:DANRE/spns1/spns1-deep-research-falcon.md "specificity for lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE)"]. The brief's "sphingolipids/sphingosine" framing is a lower-confidence secondary claim (Ha 2024 mammalian genetics); falcon notes "highest-confidence substrate assignment remains LPC/LPE". Core function kept as lysophospholipid efflux.
• Localization corroborated: lysosomal/late-endosomal membrane, LAMP1/Rab7 colocalization.
• Mechanism: pH-dependent (acidic optimum ~5-6), proton-coupled; conserved residues R76, E164, H427 required.
• New zebrafish-specific process: endocardial-autonomous spns1 drives cardiac valve morphogenesis via notch1 signaling (Chávez 2024) — noted in description but not added as a NEW annotation (no curated PMID cached; would require IC/primary-PMID pairing).
• MF term check (OLS): GO:0051978 "lysophospholipid:sodium symporter activity" is the only lysophospholipid transporter MF term but is Na+-coupled (spns1 is H+-coupled efflux), and GO:0005548 is obsolete — so the proposed_new_terms entry for proton-dependent lysophospholipid efflux remains justified; justification updated accordingly.
• No falcon contradictions to existing actions; the PMID:24967584 "H+-carbohydrate transporter" hypothesis is now flagged as superseded by the LPC/LPE transporter demonstration.

PR #1055 review response (2026-05)

• IMPORTANT: Added PMID:36161949 (He et al. 2022 PNAS, the primary substrate-deorphanization paper, DOI 10.1073/pnas.2210353119) as a formal reference with two ABSTRACT-verbatim findings. Cached via fetch-gene-pmids. Updated proposed_new_terms justification to cite PMID:36161949 explicitly.
• SUGGESTION: GO:0055085 ACCEPT → MODIFY to GO:0051977 "lysophospholipid transport" (OLS-verified valid, non-obsolete BP; child of lipid transport GO:0006869 under transport GO:0006810 — same BP aspect, more specific). core_functions.directly_involved_in updated GO:0055085 → GO:0051977 for consistency.
• SUGGESTION: Added explicit OLS-verification note for proposed_parent GO:0015562 (efflux transmembrane transporter activity; non-obsolete MF, child of GO:0022857 under GO:0005215).
• SUGGESTION: Added Chávez et al. 2024 iScience (PMID:39720516, DOI 10.1016/j.isci.2024.111406) and Ha et al. 2024 JCI Insight (PMID:38451736, DOI 10.1172/jci.insight.175462) as formal references with abstract-verbatim findings; cited both PMIDs in the description. PMIDs/DOIs confirmed via PubMed and cross-checked against the falcon report DOIs.

Re-review 2026-09-29

• Resolved 4 PENDING GOA rows (all IGI/IMP from PMID:24967584), all set KEEP_AS_NON_CORE consistent with their reviewed sibling rows: GO:0006914 autophagy, two GO:0090398 cellular senescence, GO:0097352 autophagosome maturation. These are downstream consequences of the lysosomal transporter defect (participation test: spns1 does not perform work within autophagy/senescence; it maintains lysosomal lipid homeostasis) PMID:24967584, PMID:24967584.
• Strengthened supported_by on the transporter-activity (GO:0022857 IBA/IEA ACCEPT) and transmembrane-transport (GO:0055085 MODIFY->GO:0051977) rows and on core_functions with verbatim primary quotes from He 2022 (full text now cached): PMID:36161949 and the zebrafish-specific validation PMID:36161949. Note: the direct transport assay in He 2022 used codon-optimized human SPNS1 in HeLa cells; zebrafish evidence is the whole-embryo lipidomic accumulation phenotype, and UniProt lists the zebrafish CATALYTIC ACTIVITY reactions by similarity to human Q9H2V7 — so the MF ACCEPT rests on cross-species homology plus the zebrafish accumulation phenotype, which is appropriate.
• Added reference_review (relevance/correctness/notes) to all four PMID references; all VERIFIED against cached full text.
• No REMOVE actions; no NEW terms added (endocardial valve-morphogenesis role from PMID:39720516 kept as description context only, not annotated). Validation: zero errors, zero warnings.