HSPA12A PN Consistency Notes

• Generated: 2026-06-18
• Project: PROTEOSTASIS
• Scope: priority-only PN rereview against local AIGR review and available deep-research artifacts
• UniProt: O43301
• AIGR review status: COMPLETE
• Priority category: domain_exception
• Local AIGR project status: local_review_complete_not_phase1
• Related project: UNFOLDED_PROTEIN_BINDING.md

Source Files Checked

• AIGR review YAML: present - genes/human/HSPA12A/HSPA12A-ai-review.yaml
• AIGR review HTML: present - genes/human/HSPA12A/HSPA12A-ai-review.html
• Gene notes: present - genes/human/HSPA12A/HSPA12A-notes.md
• GOA TSV: present - genes/human/HSPA12A/HSPA12A-goa.tsv
• UniProt record: present - genes/human/HSPA12A/HSPA12A-uniprot.txt
• PROTEOSTASIS priority table: projects/PROTEOSTASIS/priority_genes.tsv
• 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
• PN mapping file: none from current projection rows.

Deep Research Files

• genes/human/HSPA12A/HSPA12A-deep-research-falcon.md

AIGR Review Snapshot

• Description: HSPA12A is an atypical and still poorly characterized HSP70-family protein. The strongest direct mechanistic evidence supports ATP/ADP-sensitive binding to the cytosolic tail of SORL1/SorLA and modulation of SorLA trafficking, while later disease- and tissue-specific studies suggest context-dependent signaling or scaffold-like roles rather than a conserved GO-ready core activity. Current evidence supports a narrow SorLA/SORL1-selective adaptor-like trafficking role and does not establish canonical ATP-dependent protein folding chaperone activity or another broad core proteostasis function for HSPA12A.
• Existing/core annotation action counts: KEEP_AS_NON_CORE: 5; MARK_AS_OVER_ANNOTATED: 3; MODIFY: 1; NEW: 1

PN Consistency Summary

• Consistency: Priority-only record; no phase-1 dossier section exists yet. Local review status is local_review_complete_not_phase1. PN placement: Cytonuclear proteostasis > Chaperone > HSP70 system > HSP70. Main issue: MS1 inclusion is based on HSP70 architecture, but review supports SorLA/SORL1-tail adaptor trafficking rather than canonical HSP70 folding activity
• PN story / NEW pressure: No current projected GO row; the value is exception/context tracking.
• Mapping strategy: Keep as an explicit exception to family/domain propagation. The PN family placement is informative, but the local review should decide whether canonical chaperone activity is actually supported.
• Verdict: Record as HSP70 GO:0140662 gene exception and sync the domain-only caveat to PN

Priority Review Context

• Category: domain_exception
• PN annotations: Cytonuclear proteostasis > Chaperone > HSP70 system > HSP70
• Why interesting: MS1 inclusion is based on HSP70 architecture, but review supports SorLA/SORL1-tail adaptor trafficking rather than canonical HSP70 folding activity
• Suggested next step: Record as HSP70 GO:0140662 gene exception and sync the domain-only caveat to PN
• Related project: UNFOLDED_PROTEIN_BINDING.md

PN Projection Rows

• No current PN projected GO row for this gene. Treat this priority item as an exception, boundary, or context-tracking case rather than a direct GO propagation candidate.

PN Dossier Context

No phase-1 dossier exists for this priority-only gene. This note preserves the current PROTEOSTASIS boundary or exception decision and should be superseded by a dossier section if the gene is promoted into a full phase-1 batch.

Note

This file is generated from the current PROTEOSTASIS priority table, PN projection outputs, and local gene-review artifacts. Edit those source records rather than this generated note when correcting the underlying curation.