LAMP1 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: P11279
- AIGR review status: COMPLETE
- Review batch: proteostasis-pr-1217 (PR 1217)
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: LAMP1 encodes lysosome-associated membrane glycoprotein 1, an abundant heavily glycosylated single-pass membrane protein of lysosomes, late endosomes, and lysosome-related secretory granules. Its most informative current molecular function is direct inhibition of the lysosomal TMEM175 cation/proton channel, supporting lysosomal lumen acidification and hydrolase activity. LAMP1 also participates in lysosome-related immune granule contexts, TAPL/ABCB9 stabilization, Lassa virus receptor activity, and plasma membrane exposure during degranulation, but its core biology is centered on lysosomal and late-endosomal membrane function.
- Existing/core annotation action counts: ACCEPT: 15; KEEP_AS_NON_CORE: 35; MARK_AS_OVER_ANNOTATED: 7; MODIFY: 25; REMOVE: 2
PN Consistency Summary
- Consistency: Consistent. PN note ("LAMP1 recruits clathrin to tubules during ALR") is acknowledged in LAMP1-notes.md, which states the cached Rong et al. ALR abstract (PMID:22885770) supports clathrin/PI(4,5)P2 as ALR components but gives no LAMP1-specific statement. Review therefore does not add an ALR annotation and treats GO:0000421/GO:0044754 (autophagosome/autolysosome) as MARK_AS_OVER_ANNOTATED / KEEP_AS_NON_CORE. No contradiction.
- PN story / NEW pressure: PN asserts a LAMP1 ALR-morphology role absent from GO, but the node projects nothing and the review correctly judges the evidence insufficient. The review's own NEW pressure is elsewhere: a proposed_new_term "lysosomal proton channel inhibitor activity" (parent GO:0008200) for the TMEM175 mechanism (PMID:37390818). I verified via OLS that no such GO term exists, so this is a defensible new-term candidate, not already captured; the existing GO:0008200 ion channel inhibitor activity is the best current term and is ACCEPTed. Conclusion: ALR over-reaches; TMEM175-inhibitor new term is justified (candidate).
- Evidence alignment: PN cites one ALR review ("Membrane Trafficking in Autophagy"); review's load-bearing evidence is independent (PMID:37390818 TMEM175, PMID:23632890 NK granules, PMID:22641697 TAPL). Divergence is expected: PN row is search context, not the core LAMP1 function.
- Verdict: Consistent; PN ALR story correctly not propagated. TMEM175 proton-channel-inhibitor proposed new term is a real GO gap. No edits required.
Full Consistency Review
- UniProt: P11279 · batch: proteostasis-pr-1217 · review status: COMPLETE
- PN placement:
ALP|Autophagic lysosome reformation|Regulation of autolysosome morphology ; PN-node mapping: group no_mapping; parent class context_only / too_broad_to_propagate / GO:0007040 lysosome organization; branch no_mapping. No projected GO terms.
- Consistency: Consistent. PN note ("LAMP1 recruits clathrin to tubules during ALR") is acknowledged in LAMP1-notes.md, which states the cached Rong et al. ALR abstract (PMID:22885770) supports clathrin/PI(4,5)P2 as ALR components but gives no LAMP1-specific statement. Review therefore does not add an ALR annotation and treats GO:0000421/GO:0044754 (autophagosome/autolysosome) as MARK_AS_OVER_ANNOTATED / KEEP_AS_NON_CORE. No contradiction.
- PN story / NEW pressure: PN asserts a LAMP1 ALR-morphology role absent from GO, but the node projects nothing and the review correctly judges the evidence insufficient. The review's own NEW pressure is elsewhere: a proposed_new_term "lysosomal proton channel inhibitor activity" (parent GO:0008200) for the TMEM175 mechanism (PMID:37390818). I verified via OLS that no such GO term exists, so this is a defensible new-term candidate, not already captured; the existing GO:0008200 ion channel inhibitor activity is the best current term and is ACCEPTed. Conclusion: ALR over-reaches; TMEM175-inhibitor new term is justified (candidate).
- Mapping strategy: No change.
no_mapping for the ALR-morphology container is correct (descendants mix components/regulators); the context_only lysosome-organization framing at the class level is right. LAMP1 does not justify upgrading the node to propagation.
- Evidence alignment: PN cites one ALR review ("Membrane Trafficking in Autophagy"); review's load-bearing evidence is independent (PMID:37390818 TMEM175, PMID:23632890 NK granules, PMID:22641697 TAPL). Divergence is expected: PN row is search context, not the core LAMP1 function.
- Verdict: Consistent; PN ALR story correctly not propagated. TMEM175 proton-channel-inhibitor proposed new term is a real GO gap. No edits required.
PN Dossier Context
- review_batch: proteostasis-pr-1217
- review_yaml: genes/human/LAMP1/LAMP1-ai-review.yaml
- PN workbook rows: 1
- UniProt: P11279
- In branches: ALP
- Notes: Recruits clathrin to tubules during ALR
- PN references (titles):
- Membrane Trafficking in Autophagy - ScienceDirect
- PN-node mapping records (path + ancestors):
- [group] Autophagy-Lysosome Pathway|Autophagic lysosome reformation|Regulation of autolysosome morphology
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagic lysosome reformation
status=context_only scope=too_broad_to_propagate GO=[GO:0007040 lysosome organization]
rationale: Autophagic lysosome reformation is the lysosome-regeneration phase that follows autolysosome formation and cargo degradation. As a class, it is better aligned to lysosome organization than to generic autophagy, but the PN members are mechanistically mixed across membrane remodeling, tubulation, product efflux, and unknown late-stage roles, so class-level propagation would still over-annotate.
- [branch] Autophagy-Lysosome Pathway
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.