CHMP4A PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q9BY43
- 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: CHMP4A encodes a Snf7-family core subunit of ESCRT-III. Its best-supported function is non-enzymatic ESCRT-III polymerization on endosomal/MVB and related membranes, where CHMP4A-containing filaments bend membranes and support reverse-topology budding/fission for intraluminal vesicle formation, MVB cargo sorting, and downstream endolysosomal degradation. CHMP4A also participates in autophagy/autophagosome contexts, plasma membrane repair, cytokinetic abscission, nuclear envelope repair, and viral budding as topologically related ESCRT output contexts, but those should not obscure the core ESCRT-III membrane-remodeling role.
- Existing/core annotation action counts: ACCEPT: 38; KEEP_AS_NON_CORE: 48; MARK_AS_OVER_ANNOTATED: 10; MODIFY: 6; NEW: 1; REMOVE: 1
PN Consistency Summary
- Consistency: Consistent. The review ACCEPTs GO:0000815 ESCRT III complex (IBA + NAS) and the autophagy/endolysosomal context cluster (GO:0006914, GO:0097352 autophagosome maturation, GO:0000421 autophagosome membrane, GO:1902774, GO:1904930 amphisome). The review's own caveat — CHMP4A "was [not] directly assayed as the phagophore-sealing effector" (Snf7-1 knockdown causes autophagosome accumulation, PMID:21975012/17984323) — matches PN routing "sealing" to the safe parent GO:0000045 rather than a sealing-specific term. No contradiction.
- PN story / NEW pressure: Already captured. Verified via OLS that no GO term for "autophagosome closure / phagophore sealing" exists (GO:0061908 phagophore is a CC only; GO:0000045 is the narrowest process). PN's "sealing" projection therefore correctly degrades to GO:0000045 — but the review does not list GO:0000045 for CHMP4A, instead carrying GO:0097352 autophagosome maturation (a sibling) + GO:0006914. Both are defensible; GO:0000045 would be the assembly-side framing of the same sealing biology.
- Evidence alignment: Minimal overlap. PN cites one MDPI review "Key Regulators of Autophagosome Closure"; the review uses none of PN's citations, relying on primary ESCRT-III structural/functional literature (PMID:18209100, 19234443, 17984323, 21975012). Convergent on the ESCRT-III-in-autophagosome-closure concept via independent sources.
- Verdict: Consistent; PN projections (GO:0000815, GO:0000045) are both ≤ existing or more-specific. Optional edit: reconcile GO:0000045 vs the review's GO:0097352 for the sealing step.
Full Consistency Review
- UniProt: Q9BY43 · batch: proteostasis-pr-1217 · review status: COMPLETE
- PN placement: 2 rows, ALP — (1)
Autophagosome closure maturation and lysosome fusion → Sealing of autophagophore membrane → ESCRT-III complex component; (2) Microautophagy → General microautophagy machinery → ESCRT-III complex component. PN-node mapping: ESCRT-III leaves=mapped→GO:0000815 (already_in_goa_exact); sealing group=mapped→GO:0000045 autophagosome assembly (more_specific_than_existing_goa); ancestors context_only (GO:0016236, GO:0016237). Projected: GO:0000815 (x2), GO:0000045.
- Consistency: Consistent. The review ACCEPTs GO:0000815 ESCRT III complex (IBA + NAS) and the autophagy/endolysosomal context cluster (GO:0006914, GO:0097352 autophagosome maturation, GO:0000421 autophagosome membrane, GO:1902774, GO:1904930 amphisome). The review's own caveat — CHMP4A "was [not] directly assayed as the phagophore-sealing effector" (Snf7-1 knockdown causes autophagosome accumulation, PMID:21975012/17984323) — matches PN routing "sealing" to the safe parent GO:0000045 rather than a sealing-specific term. No contradiction.
- PN story / NEW pressure: Already captured. Verified via OLS that no GO term for "autophagosome closure / phagophore sealing" exists (GO:0061908 phagophore is a CC only; GO:0000045 is the narrowest process). PN's "sealing" projection therefore correctly degrades to GO:0000045 — but the review does not list GO:0000045 for CHMP4A, instead carrying GO:0097352 autophagosome maturation (a sibling) + GO:0006914. Both are defensible; GO:0000045 would be the assembly-side framing of the same sealing biology.
- Recommended edits: consider adding
GO:0000045 autophagosome assembly (action: NEW or note in suggested_questions) to align with the PN "Sealing of autophagophore membrane → autophagosome assembly" projection, OR explicitly note GO:0097352 already covers the closure/maturation step. Low priority — the maturation term already captures the biology; flag for curator.
- Mapping strategy: No change needed. GO:0000815 is already_in_goa_exact (safe). GO:0000045 is more_specific_than_existing_goa (good direction, not over-reach). CHMP4A is a clean ESCRT-III member for both the autophagosome-closure and microautophagy leaves; the node mappings are appropriate.
- Evidence alignment: Minimal overlap. PN cites one MDPI review "Key Regulators of Autophagosome Closure"; the review uses none of PN's citations, relying on primary ESCRT-III structural/functional literature (PMID:18209100, 19234443, 17984323, 21975012). Convergent on the ESCRT-III-in-autophagosome-closure concept via independent sources.
- Verdict: Consistent; PN projections (GO:0000815, GO:0000045) are both ≤ existing or more-specific. Optional edit: reconcile GO:0000045 vs the review's GO:0097352 for the sealing step.
PN Dossier Context
- review_batch: proteostasis-pr-1217
- review_yaml: genes/human/CHMP4A/CHMP4A-ai-review.yaml
- PN workbook rows: 2
PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | ESCRT-III complex component
- UniProt: Q9BY43
- In branches: ALP
- Notes: Component of the ESCRT-III complex, involved in autophagosome closure
- PN references (titles):
- Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
- PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-III complex component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000815 ESCRT III complex]
rationale: This PN type is a structural component class for ESCRT-III factors used in autophagophore sealing. The matching GO cellular-component term is ESCRT III complex, which is more precise than the broader late-fusion process mapping.
- [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
- [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
- [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.
PN row 2: Autophagy-Lysosome Pathway | Microautophagy | General microautophagy machinery | ESCRT-III complex component
- UniProt: Q9BY43
- In branches: ALP
- PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery|ESCRT-III complex component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0000815 ESCRT III complex]
rationale: This leaf is a component bucket for ESCRT-III machinery used in microautophagy contexts. The shared GO assertion is ESCRT III complex membership.
- [group] Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery
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|Microautophagy
status=context_only scope=too_broad_to_propagate GO=[GO:0016237 microautophagy]
rationale: The class names a real GO process, but the subtree includes machinery components and mitochondrion-derived-vesicle contexts as well as process labels. Propagation is restricted to narrower nodes.
- [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.
Projected GO annotations (3)
- GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
- GO:0000815 ESCRT III complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|ESCRT-III complex component
- GO:0000815 ESCRT III complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Microautophagy|General microautophagy machinery|ESCRT-III complex component
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.