ZFYVE26 PN Consistency Notes

• Generated: 2026-06-18
• Project: PROTEOSTASIS
• Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
• UniProt: Q68DK2
• AIGR review status: COMPLETE
• Review batch: proteostasis-pr-1217 (PR 1217)
• Batch change status: added

Source Files Checked

• AIGR review YAML: present - genes/human/ZFYVE26/ZFYVE26-ai-review.yaml
• AIGR review HTML: present - genes/human/ZFYVE26/ZFYVE26-ai-review.html
• Gene notes: present - genes/human/ZFYVE26/ZFYVE26-notes.md
• GOA TSV: present - genes/human/ZFYVE26/ZFYVE26-goa.tsv
• UniProt record: present - genes/human/ZFYVE26/ZFYVE26-uniprot.txt
• PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/ZFYVE26.md
• PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/ZFYVE26.md
• PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
• PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

• No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

• Description: ZFYVE26 encodes spastizin/SPG15, a FYVE-domain PI3P-binding protein that functions with SPG11/spatacsin and AP-5 in endolysosomal membrane remodeling. The strongest protein-homeostasis evidence supports a core role in autophagic lysosome reformation, lysosomal membrane organization, membrane bending, and autophagosome maturation through PI3P-dependent recruitment to lysosomal/late-endosomal membranes. ZFYVE26 also has experimentally supported cytokinesis and HR-DSBR roles, but its principal cellular role is endolysosomal membrane remodeling.
• Existing/core annotation action counts: ACCEPT: 16; KEEP_AS_NON_CORE: 12; MARK_AS_OVER_ANNOTATED: 1; MODIFY: 8; NEW: 1; UNDECIDED: 1

PN Consistency Summary

• Consistency: Strongly consistent. Deep-research notes, review YAML, PN notes, and PN mappings all converge: core = PI3P-binding FYVE protein in AP5-SPG11-SPG15 endolysosomal membrane remodeling / ALR / autophagosome maturation. The PN note's "Beclin1-UVRAG-Rubicon… required for autophagosome maturation" matches the review's NEW GO:0097352 row. No contradictions.
• PN story / NEW pressure: PN asserts (a) class III PI3K complex modulation — review correctly does NOT claim complex membership, using GO:0032266 PI3P binding + lysosome organization instead (matches PN's context_only decision); and (b) ALR with "specific function unknown." Review supplies the mechanism: GO:0007040, GO:0097212 lysosomal membrane organization, GO:0097753 membrane bending, plus NEW GO:0097352 autophagosome maturation (OLS-verified real). ALR itself has no GO term (OLS search empty) — review's proposed_new_terms "autophagic lysosome reformation" under GO:0007040 is well-justified. Conclusion: NEW term (ALR) defensible; autophagosome maturation is a defensible ADD already in review; class-III-PI3K membership correctly NOT added.
• Evidence alignment: Both PN refs are in the review. PN "Defective autophagy in spastizin… HSP type 15" = PMID:24030950 (autophagosome maturation); PN "spastizin and spatacsin mediate ALR" = PMID:25365221 (lysosome organization/ALR). Review adds PMID:40175557 (2025 structure), 23825025 (AP-5), 37871017, 20208530 the PN rows omit.
• Verdict: Fully consistent; review enriches the PN "function unknown" ALR node with verified terms (GO:0097352 add + ALR proposed-new-term). Mappings sound; no demotions needed.

Full Consistency Review

• UniProt: Q68DK2 (spastizin/SPG15/FYVE-CENT) · batch: proteostasis-pr-1217 · review status: COMPLETE
• PN placement: ALP|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Modulator of class 3 PI3K complex 2 activity and ALP|Autophagic lysosome reformation|Specific function… unknown ; PN-node mapping: PI3K-complex nodes all context_only/too_broad → GO:0035032 (class III PI3K complex), explicitly "should not project CC membership"; ALR group = no_mapping (unknown); ALR class = context_only → GO:0007040 lysosome organization.
• Consistency: Strongly consistent. Deep-research notes, review YAML, PN notes, and PN mappings all converge: core = PI3P-binding FYVE protein in AP5-SPG11-SPG15 endolysosomal membrane remodeling / ALR / autophagosome maturation. The PN note's "Beclin1-UVRAG-Rubicon… required for autophagosome maturation" matches the review's NEW GO:0097352 row. No contradictions.
• PN story / NEW pressure: PN asserts (a) class III PI3K complex modulation — review correctly does NOT claim complex membership, using GO:0032266 PI3P binding + lysosome organization instead (matches PN's context_only decision); and (b) ALR with "specific function unknown." Review supplies the mechanism: GO:0007040, GO:0097212 lysosomal membrane organization, GO:0097753 membrane bending, plus NEW GO:0097352 autophagosome maturation (OLS-verified real). ALR itself has no GO term (OLS search empty) — review's proposed_new_terms "autophagic lysosome reformation" under GO:0007040 is well-justified. Conclusion: NEW term (ALR) defensible; autophagosome maturation is a defensible ADD already in review; class-III-PI3K membership correctly NOT added.
• Mapping strategy: No change needed to PI3K nodes (context_only is right; precedent-aligned — narrower review terms, no spurious CC propagation). ALR group could be upgraded from no_mapping toward GO:0007040 lysosome organization (the review's accepted core, and the class-node target), but PN's "unknown specific function" caution is reasonable; review is narrower than the PN class-level GO:0007040, never broader.
• Evidence alignment: Both PN refs are in the review. PN "Defective autophagy in spastizin… HSP type 15" = PMID:24030950 (autophagosome maturation); PN "spastizin and spatacsin mediate ALR" = PMID:25365221 (lysosome organization/ALR). Review adds PMID:40175557 (2025 structure), 23825025 (AP-5), 37871017, 20208530 the PN rows omit.
• Verdict: Fully consistent; review enriches the PN "function unknown" ALR node with verified terms (GO:0097352 add + ALR proposed-new-term). Mappings sound; no demotions needed.

PN Dossier Context

• review_batch: proteostasis-pr-1217
• review_yaml: genes/human/ZFYVE26/ZFYVE26-ai-review.yaml
• PN workbook rows: 2

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Class 3 PI3K complex 2, direct | Modulator of class 3 PI3K complex 2 activity

• UniProt: Q68DK2
• In branches: ALP
• Notes: aka FYVE-CENT, SPG15, and spastizin. Spastizin interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex and is required for autophagosome maturation. In cells lacking spastizin or with mutated forms of the protein, spastizin interaction with Beclin 1 is lost although the formation of the Beclin 1-UVRAG-Rubicon complex can still be observed. However, in these cells there is an impairment of autophagosome maturation and an accumulation of immature autophagosomes. Also important in autophagic lysosomal reformation.
• PN references (titles):
  • Defective autophagy in spastizin mutated patients with hereditary spastic paraparesis type 15 | Brain | Oxford Academic (oup.com)
  • JCI - Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation
• PN-node mapping records (path + ancestors):
  • [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct|Modulator of class 3 PI3K complex 2 activity
    status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
    rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
  • [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Class 3 PI3K complex 2, direct
    status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
    rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
  • [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 | Autophagic lysosome reformation | Specific function in autophagic lysosome reformation unknown

• UniProt: Q68DK2
• In branches: ALP
• Notes: aka FYVE-CENT, SPG15, and spastizin. Spastizin interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex and is required for autophagosome maturation. In cells lacking spastizin or with mutated forms of the protein, spastizin interaction with Beclin 1 is lost although the formation of the Beclin 1-UVRAG-Rubicon complex can still be observed. However, in these cells there is an impairment of autophagosome maturation and an accumulation of immature autophagosomes. Also important in autophagic lysosomal reformation.
• PN references (titles):
  • Defective autophagy in spastizin mutated patients with hereditary spastic paraparesis type 15 | Brain | Oxford Academic (oup.com)
  • JCI - Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation
• PN-node mapping records (path + ancestors):
  • [group] Autophagy-Lysosome Pathway|Autophagic lysosome reformation|Specific function in autophagic lysosome reformation unknown
    status=no_mapping scope= GO=[]
    rationale: This PN group explicitly states that the specific role within autophagic lysosome reformation is unknown. That makes GO propagation unsafe until a narrower mechanistic interpretation is available.
  • [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.