LMAN2L PN Consistency Notes

• Generated: 2026-06-18
• Project: PROTEOSTASIS
• Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
• UniProt: Q9H0V9
• AIGR review status: COMPLETE
• Review batch: proteostasis-batch-2026-06-11
• Batch change status: added

Source Files Checked

• AIGR review YAML: present - genes/human/LMAN2L/LMAN2L-ai-review.yaml
• AIGR review HTML: missing - genes/human/LMAN2L/LMAN2L-ai-review.html
• Gene notes: present - genes/human/LMAN2L/LMAN2L-notes.md
• GOA TSV: present - genes/human/LMAN2L/LMAN2L-goa.tsv
• UniProt record: present - genes/human/LMAN2L/LMAN2L-uniprot.txt
• PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/LMAN2L.md
• PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/LMAN2L.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/LMAN2L/LMAN2L-deep-research-falcon.md

AIGR Review Snapshot

• Description: LMAN2L (VIPL, "VIP36-like protein") is an ER-resident L-type (leguminous/ConA-like) lectin and a paralog of VIP36/LMAN2 and ERGIC-53/LMAN1. It is a single-pass type I membrane glycoprotein whose N-terminal luminal L-type lectin carbohydrate-recognition domain binds high-mannose glycans (D-mannose) and whose short cytoplasmic tail carries an RKR di-arginine ER-retention signal. Unlike the cycling lectins VIP36 and ERGIC-53, LMAN2L is predominantly a non-cycling resident of the endoplasmic reticulum, with a minor Golgi pool. It is not a glycosidase and has no catalytic activity; rather it is proposed to regulate ER export of a subset of glycoproteins and to act as a regulator of ERGIC-53, with overexpression redistributing ERGIC-53 to the ER and knockdown slowing glycoprotein secretion. LMAN2L is a neurodevelopmental disease gene: variants cause autosomal recessive (MRT52) and autosomal dominant (MRD69) intellectual developmental disorders.
• Existing/core annotation action counts: ACCEPT: 9; KEEP_AS_NON_CORE: 7; MARK_AS_OVER_ANNOTATED: 3

PN Consistency Summary

• Consistency: Deep research ↔ review ↔ PN annotation consistent. VIPL is an L-type lectin, NOT a glycosidase — matching the "Lectin chaperone" type. Distinctive vs its cycling paralogs: it is a non-cycling ER-resident (RKR retention) regulator of ER export / regulator of ERGIC-53 (core BP GO:0006888, GO:0015031). D-mannose binding accepted as a homology/CRD-based MF (no direct binding assay for VIPL itself — review states this clearly). No contradictions.
• PN story / NEW pressure: No NEW GO pressure. ER-export-receptor / ERGIC-53-regulator role is captured by transport terms; a candidate physiological client (ITGA6, via PMID:38687323) is noted but single-paper/candidate-stage and the review correctly did not mint a term. Conclude: already captured.
• Evidence alignment: PN dossier is mapping-only. Review evidence centers on PMID:12609988 and PMID:12878160 (PubMed-verified primary papers) plus disease PMIDs (26566883, 31020005, 37667433) and HCMV/TRC8 (38687323). No bibliographic conflict; divergence is conceptual (group biosynthesis term vs. lectin/ER-export function).
• Verdict: Review strong and PN-consistent (ER-resident lectin/export regulator, not a mannosidase). Inherited group→GO:0006487 projection is an over-reach.

Full Consistency Review

• UniProt: Q9H0V9 (VIP36-like protein / VIPL) · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE, thorough (two primary characterizations + disease + Falcon).
• PN placement: ER proteostasis|Glycoproteostasis|N-glycosylation system|Lectin chaperone ; PN-node mapping: type "Lectin chaperone" no_mapping; group "N-glycosylation system" mapped→GO:0006487 (protein N-linked glycosylation, ok_for_propagation, new_to_goa); class/branch no_mapping.
• Consistency: Deep research ↔ review ↔ PN annotation consistent. VIPL is an L-type lectin, NOT a glycosidase — matching the "Lectin chaperone" type. Distinctive vs its cycling paralogs: it is a non-cycling ER-resident (RKR retention) regulator of ER export / regulator of ERGIC-53 (core BP GO:0006888, GO:0015031). D-mannose binding accepted as a homology/CRD-based MF (no direct binding assay for VIPL itself — review states this clearly). No contradictions.
• PN story / NEW pressure: No NEW GO pressure. ER-export-receptor / ERGIC-53-regulator role is captured by transport terms; a candidate physiological client (ITGA6, via PMID:38687323) is noted but single-paper/candidate-stage and the review correctly did not mint a term. Conclude: already captured.
• Mapping strategy: Group→GO:0006487 (new_to_goa) over-reaches as for the other lectins — VIPL reads/exports high-mannose glycoproteins; it does not perform N-linked glycosylation. Additionally, VIPL is predominantly ER-resident (not a classic ERGIC cycler), so even the family-level "N-glycosylation system" framing fits it least well. PN node correct to leave "Lectin chaperone" unmapped; projected term should not propagate.
• Evidence alignment: PN dossier is mapping-only. Review evidence centers on PMID:12609988 and PMID:12878160 (PubMed-verified primary papers) plus disease PMIDs (26566883, 31020005, 37667433) and HCMV/TRC8 (38687323). No bibliographic conflict; divergence is conceptual (group biosynthesis term vs. lectin/ER-export function).
• Verdict: Review strong and PN-consistent (ER-resident lectin/export regulator, not a mannosidase). Inherited group→GO:0006487 projection is an over-reach.
  Recommended edits: [MAP] Do not propagate GO:0006487 (protein N-linked glycosylation) to LMAN2L/VIPL — it is an ER-resident high-mannose lectin / ER-export regulator, not an N-glycosylation enzyme; flag the "N-glycosylation system" group node as over-broad (and a poor fit for a non-cycling ER resident).

PN Dossier Context

• review_batch: proteostasis-batch-2026-06-11
• review_yaml: genes/human/LMAN2L/LMAN2L-ai-review.yaml
• PN workbook rows: 1

PN row 1: ER proteostasis | Glycoproteostasis | N-glycosylation system | Lectin chaperone

• UniProt: Q9H0V9
• In branches: ER
• PN-node mapping records (path + ancestors):
  • [type] ER proteostasis|Glycoproteostasis|N-glycosylation system|Lectin chaperone
    status=no_mapping scope= GO=[]
    rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
  • [group] ER proteostasis|Glycoproteostasis|N-glycosylation system
    status=mapped scope=ok_for_propagation_to_go GO=[GO:0006487 protein N-linked glycosylation]
    rationale: This PN group captures the ER N-glycosylation machinery that installs and processes N-linked glycans during proteostasis. GO protein N-linked glycosylation is the best current propagation target in the local cache.
  • [class] ER proteostasis|Glycoproteostasis
    status=no_mapping scope= GO=[]
    rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
  • [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 (1)

• GO:0006487 protein N-linked glycosylation | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Glycoproteostasis|N-glycosylation system

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.