ATP6AP1 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q15904
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-03 (PR 1383)
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: ATP6AP1 encodes V-type proton ATPase subunit S1, also known as Ac45, a single-pass glycoprotein accessory subunit of the vacuolar H+-ATPase. It is synthesized in the secretory pathway, localizes prominently to the ER and ER-Golgi intermediate compartment in hepatocytes, and is incorporated into the V0 sector of mature V-ATPase complexes in endolysosomal and specialized secretory membranes. ATP6AP1 supports V-ATPase assembly, targeting, stability, and activity, thereby contributing to acidification of lysosomes, endosomes, Golgi/secretory compartments, and specialized plasma-membrane domains. Through the lysosomal V-ATPase-Ragulator machinery it contributes to amino-acid-dependent mTORC1 signaling, and disruption of V-ATPase function secondarily affects iron handling and HIF1alpha regulation. Pathogenic ATP6AP1 variants cause an X-linked disorder with immunodeficiency, hepatopathy, cognitive or neurologic features, and abnormal protein glycosylation, consistent with tissue-specific defects in V-ATPase assembly and organelle homeostasis.
- Existing/core annotation action counts: ACCEPT: 26; KEEP_AS_NON_CORE: 13; MARK_AS_OVER_ANNOTATED: 11; MODIFY: 2; NEW: 1; REMOVE: 2
PN Consistency Summary
- Consistency: Deep research/notes, review, and PN agree: ATP6AP1/Ac45 is an accessory V0 assembly-hub/regulatory subunit (PMID:33065002, PMID:27231034). Review adds GO:0060590 (action NEW, IC) and ACCEPTs GO:0007042 — exactly matching both PN projections. Verified: GO:0060590 absent from goa.tsv (genuinely new); GO:0007042 present (NAS, ComplexPortal) confirming "already_in_goa_exact". No contradictions.
- PN story / NEW pressure: PN asserts a regulator MF not previously in GOA. Review correctly converts the legacy GO:0140677 (molecular function activator activity) → GO:0060590 and adds it as NEW core MF. GO:0060590 is a real term and the conservative right target (vs. uninformative protein binding, six of which are MARK_AS_OVER_ANNOTATED). ADD GO:0060590 — implemented.
- Evidence alignment: PN cites one title (Translational Neurodegeneration V-ATPase/lysosomal acidification review); review's supporting PMIDs (33065002 structural, 27231034 disease/localization, 22053050 mTORC1) are stronger and fully cover the claims. Minor: PN's single secondary-review citation is thinner than the review's primary set, but no conflict.
- Verdict: CONSISTENT — NEW GO:0060590 (verified real) appropriately added; PN leaf and acidification mappings align with review. No edits required.
Full Consistency Review
- UniProt: Q15904 · batch: proteostasis-batch-2026-06-03 · review status: COMPLETE
- PN placement: two rows, both leaf "Regulator of the lysosomal v-ATPase proton pump": (1)
ALP|Pre-initiation autophagy signaling|mTORC1 upstream|Nutrient sensing|... and (2) ALP|Lysosomal catabolism|Regulation of lysosomal environment|Lysosomal acidification|.... PN-node mapping: leaves = mapped, GO:0060590 ATPase regulator activity (new_to_goa); plus type-node GO:0007042 lysosomal lumen acidification (already_in_goa_exact).
- Consistency: Deep research/notes, review, and PN agree: ATP6AP1/Ac45 is an accessory V0 assembly-hub/regulatory subunit (PMID:33065002, PMID:27231034). Review adds GO:0060590 (action NEW, IC) and ACCEPTs GO:0007042 — exactly matching both PN projections. Verified: GO:0060590 absent from goa.tsv (genuinely new); GO:0007042 present (NAS, ComplexPortal) confirming "already_in_goa_exact". No contradictions.
- PN story / NEW pressure: PN asserts a regulator MF not previously in GOA. Review correctly converts the legacy GO:0140677 (molecular function activator activity) → GO:0060590 and adds it as NEW core MF. GO:0060590 is a real term and the conservative right target (vs. uninformative protein binding, six of which are MARK_AS_OVER_ANNOTATED). ADD GO:0060590 — implemented.
- Mapping strategy: Gene meaningfully supports the leaf mapping (it is the archetypal "regulator of lysosomal V-ATPase"). Projected GO:0060590 is neither broader nor narrower than the review's chosen core MF — they coincide. GO:0007042 type-node projection matches existing GOA. Mapping is appropriate; no change.
- Evidence alignment: PN cites one title (Translational Neurodegeneration V-ATPase/lysosomal acidification review); review's supporting PMIDs (33065002 structural, 27231034 disease/localization, 22053050 mTORC1) are stronger and fully cover the claims. Minor: PN's single secondary-review citation is thinner than the review's primary set, but no conflict.
- Verdict: CONSISTENT — NEW GO:0060590 (verified real) appropriately added; PN leaf and acidification mappings align with review. No edits required.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-03
- review_yaml: genes/human/ATP6AP1/ATP6AP1-ai-review.yaml
- PN workbook rows: 2
PN row 1: Autophagy-Lysosome Pathway | Pre-initiation autophagy signaling | mTORC1 pathway, upstream | Nutrient sensing | Regulator of the lysosomal v-ATPase proton pump
- UniProt: Q15904
- In branches: ALP
- Notes: Adapter protein for v-ATPase and its regulators
- PN references (titles):
- The emerging roles of vacuolar-type ATPase-dependent Lysosomal acidification in neurodegenerative diseases | Translational Neurodegeneration | Full Text (biomedcentral.com)
- PN-node mapping records (path + ancestors):
- [subtype] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|Nutrient sensing|Regulator of the lysosomal v-ATPase proton pump
status=mapped scope=ok_for_propagation_to_go GO=[GO:0060590 ATPase regulator activity]
rationale: This PN leaf contains ATP6AP-family regulators of the lysosomal V-ATPase. ATPase regulator activity is the safe shared molecular-function target.
- [type] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|Nutrient sensing
status=no_mapping scope= GO=[]
rationale: Reviewed as a contextual PN role. The label is useful for curator triage, but by itself does not support a universal GO assertion for all member genes beyond curated ancestor or child mappings.
- [group] Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream
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|Pre-initiation autophagy signaling
status=context_only scope=too_broad_to_propagate GO=[GO:0010506 regulation of autophagy]
rationale: This class organizes upstream signaling inputs to autophagy initiation. Because the subtree contains generic insulin, AMPK, mTORC1, nutrient-sensing, and miscellaneous signaling components, class-level propagation to regulation of autophagy would over-annotate many genes.
- [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 | Lysosomal catabolism | Regulation of lysosomal environment | Lysosomal acidification | Regulator of the lysosomal v-ATPase proton pump
- UniProt: Q15904
- In branches: ALP
- Notes: Adapter protein for v-ATPase and its regulators
- PN references (titles):
- The emerging roles of vacuolar-type ATPase-dependent Lysosomal acidification in neurodegenerative diseases | Translational Neurodegeneration | Full Text (biomedcentral.com)
- PN-node mapping records (path + ancestors):
- [subtype] Autophagy-Lysosome Pathway|Lysosomal catabolism|Regulation of lysosomal environment|Lysosomal acidification|Regulator of the lysosomal v-ATPase proton pump
status=mapped scope=ok_for_propagation_to_go GO=[GO:0060590 ATPase regulator activity]
rationale: This PN subtype is a regulator of the lysosomal V-ATPase proton pump. ATPase regulator activity is the narrowest GO target that preserves the source mechanism without requiring a speculative complex-specific term.
- [type] Autophagy-Lysosome Pathway|Lysosomal catabolism|Regulation of lysosomal environment|Lysosomal acidification
status=mapped scope=ok_for_propagation_to_go GO=[GO:0007042 lysosomal lumen acidification]
rationale: This PN group directly names the lysosomal acidification mechanism. Propagation to the GO lysosomal lumen acidification term is an exact mechanistic match.
- [group] Autophagy-Lysosome Pathway|Lysosomal catabolism|Regulation of lysosomal environment
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|Lysosomal catabolism
status=no_mapping scope= GO=[]
rationale: Reviewed as a broad lysosomal-degradation container. The subtree includes carbohydrate, lipid, protein, nuclease, phosphatase, sulfatase, and environment-regulation roles, so mapping should occur at the enzyme or process subtype level.
- [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:0060590 ATPase regulator activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|Nutrient sensing|Regulator of the lysosomal v-ATPase proton pump
- GO:0007042 lysosomal lumen acidification | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Lysosomal catabolism|Regulation of lysosomal environment|Lysosomal acidification
- GO:0060590 ATPase regulator activity | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Autophagy-Lysosome Pathway|Lysosomal catabolism|Regulation of lysosomal environment|Lysosomal acidification|Regulator of the lysosomal v-ATPase proton pump
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.