EMC9 PN Consistency Notes

• Generated: 2026-06-18
• Project: PROTEOSTASIS
• Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
• UniProt: Q9Y3B6
• AIGR review status: COMPLETE
• Review batch: proteostasis-batch-2026-06-11
• Batch change status: added

Source Files Checked

• AIGR review YAML: present - genes/human/EMC9/EMC9-ai-review.yaml
• AIGR review HTML: missing - genes/human/EMC9/EMC9-ai-review.html
• Gene notes: present - genes/human/EMC9/EMC9-notes.md
• GOA TSV: present - genes/human/EMC9/EMC9-goa.tsv
• UniProt record: present - genes/human/EMC9/EMC9-uniprot.txt
• PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/EMC9.md
• PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/EMC9.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

• genes/human/EMC9/EMC9-deep-research-falcon.md

AIGR Review Snapshot

• Description: EMC9 (ER membrane protein complex subunit 9; also FAM158A) is a 208 aa cytosolic, peripheral subunit of the ER membrane protein complex (EMC), associated with the cytoplasmic face of the ER membrane. It belongs to the EMC8/EMC9 family and contains an MPN (Mpr1/Pad1 N-terminal) domain that is degenerate and lacks the catalytic residues of active JAMM/MPN metalloproteases, so EMC9 is not predicted to have intrinsic enzymatic activity. EMC9 and its paralog EMC8 are mutually exclusive subunits of the EMC, defining alternative complex variants; EMC9 docks into the complex primarily through binding to EMC2. The EMC is a conserved transmembrane-domain insertase and membrane-protein chaperone that mediates energy-independent insertion of newly synthesized membrane proteins into the ER membrane, including post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins. As a peripheral, non-catalytic subunit, EMC9 participates in these processes through complex membership rather than direct catalysis; the membrane insertase activity resides in the EMC3/EMC6 core. EMC9 is broadly expressed and remains relatively weakly characterized.
• Existing/core annotation action counts: ACCEPT: 5; KEEP_AS_NON_CORE: 18

PN Consistency Summary

• Consistency: Deep research, review YAML, and PN annotation are consistent: EMC9 is the cytosolic, peripheral EMC8 paralog (mutually exclusive variant subunit), degenerate MPN domain, non-catalytic, docks via EMC2. The review carries the EMC9-specific developmental "foldopathy" evidence (PMID:37318954 — damaging EMC9 variants, neural-crest/WNT-Fzd7/β-catenin phenotype) not in the dossier; this is supporting, not contradictory.
• PN story / NEW pressure: PN asserts only EMC membership + import/insertion, already captured (GO:0072546 part_of; the insertion/insertase terms KEEP_AS_NON_CORE since EMC8/EMC9 are interchangeable). No NEW GO term needed. The WNT-dependent developmental role is disease context, not a new molecular/process annotation; review correctly does not elevate it.
• Evidence alignment: High overlap on the EMC insertase/structure core (22119785, 29242231, 32439656, 30415835, 32459176); review adds EMC9-specific PMID:37318954, 32332093 absent from the PN row but consistent with the membrane-protein-biogenesis framing.
• Verdict: Consistent; well-reviewed. Note EMC9's contribution is via membership only (paralog-redundant), and the shared group→GO:0044743 mapping diverges from EMC insertion semantics.

Full Consistency Review

• UniProt: Q9Y3B6 · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE
• PN placement: ER proteostasis|Protein transport|Transmembrane protein import|EMC complex component ; PN-node mapping: type → GO:0072546 (EMC complex); group → GO:0044743 (protein transmembrane import into intracellular organelle); class → GO:0015031 (protein transport); branch=no_mapping.
• Consistency: Deep research, review YAML, and PN annotation are consistent: EMC9 is the cytosolic, peripheral EMC8 paralog (mutually exclusive variant subunit), degenerate MPN domain, non-catalytic, docks via EMC2. The review carries the EMC9-specific developmental "foldopathy" evidence (PMID:37318954 — damaging EMC9 variants, neural-crest/WNT-Fzd7/β-catenin phenotype) not in the dossier; this is supporting, not contradictory.
• PN story / NEW pressure: PN asserts only EMC membership + import/insertion, already captured (GO:0072546 part_of; the insertion/insertase terms KEEP_AS_NON_CORE since EMC8/EMC9 are interchangeable). No NEW GO term needed. The WNT-dependent developmental role is disease context, not a new molecular/process annotation; review correctly does not elevate it.
• Mapping strategy: EMC9 does not change the shared node mapping (still an EMC complex member → GO:0072546). Same group-level issue as EMC7/EMC8: GO:0044743 (import into organelle interior) mismatches the EMC's membrane-protein insertion role; insertion terms are not subclasses of GO:0044743.
• Evidence alignment: High overlap on the EMC insertase/structure core (22119785, 29242231, 32439656, 30415835, 32459176); review adds EMC9-specific PMID:37318954, 32332093 absent from the PN row but consistent with the membrane-protein-biogenesis framing.
• Verdict: Consistent; well-reviewed. Note EMC9's contribution is via membership only (paralog-redundant), and the shared group→GO:0044743 mapping diverges from EMC insertion semantics.

PN Dossier Context

• review_batch: proteostasis-batch-2026-06-11
• review_yaml: genes/human/EMC9/EMC9-ai-review.yaml
• PN workbook rows: 1

PN row 1: ER proteostasis | Protein transport | Transmembrane protein import | EMC complex component

• UniProt: Q9Y3B6
• In branches: ER
• PN-node mapping records (path + ancestors):
  • [type] ER proteostasis|Protein transport|Transmembrane protein import|EMC complex component
    status=mapped scope=ok_for_propagation_to_go GO=[GO:0072546 EMC complex]
    rationale: This PN type denotes ER membrane protein complex components. The GO EMC complex cellular-component term is the direct target.
  • [group] ER proteostasis|Protein transport|Transmembrane protein import
    status=mapped scope=ok_for_propagation_to_go GO=[GO:0044743 protein transmembrane import into intracellular organelle]
    rationale: This PN group covers ER transmembrane-protein insertion/import systems such as EMC- and PAT-related pathways. The local GO cache does not expose an ER-specific matching term, so the broader intracellular-organelle transmembrane-import process is the best supported propagation target.
  • [class] ER proteostasis|Protein transport
    status=mapped scope=ok_for_propagation_to_go GO=[GO:0015031 protein transport]
    rationale: The PN ER Protein transport class groups ER-targeting and ER-insertion pathways. GO protein transport is the appropriate propagation target, while the source class remains ER-specific and broader than any single GO transport subtype.
  • [branch] ER proteostasis
    status=no_mapping scope= GO=[]
    rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (3)

• GO:0015031 protein transport | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Protein transport
• GO:0044743 protein transmembrane import into intracellular organelle | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Protein transport|Transmembrane protein import
• GO:0072546 EMC complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Protein transport|Transmembrane protein import|EMC 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.