Proteostasis Review Batch 4 — Gene Selection

Warnings (1)

Proteostasis Review Batch 4 — Gene Selection

Date: 2026-06-07
Branch: claude/proteostasis-network-genes-BVKRp

Context

The three prior batches are complete:
- proteostasis-pr-1217 (50 human genes, merged 2026-06-02)
- proteostasis-batch-2026-06-03 (50 human genes, alphabetical sweep AAAS..ATP6V0D1)
- proteostasis-batch-2026-06-06 (20 human genes; V-ATPase core, ER folding/QC,
autophagy/mitophagy receptors, co-chaperone/UPS regulation)

This batch selects 30 more genes from the PN projected candidate-additions
report (reports/pn_projection/pn_projected_candidate_additions.tsv), all of
which are PN-projected candidates with ok_for_propagation_to_go scope and had
no local *-ai-review.yaml before this batch.

Rather than continuing the pure alphabetical sweep (which next hits a long run of
family/domain-based BTB-domain inclusions of lower individual value), this batch
is chosen to be biologically coherent and high-value across the proteostasis
branches.

Selected genes (30)

ALP — lysosomal acidification (complete tissue-specific V-ATPase isoforms + Cl/H antiporter)

  1. ATP6V0E2 — V-ATPase V0 e2 subunit
  2. ATP6V1B1 — V-ATPase V1 B1 subunit (kidney/inner-ear isoform)
  3. ATP6V1C2 — V-ATPase V1 C2 subunit (lung/kidney isoform)
  4. ATP6V1E2 — V-ATPase V1 E2 subunit (testis isoform)
  5. ATP6V1G2 — V-ATPase V1 G2 subunit (neuronal isoform)
  6. ATP6V1G3 — V-ATPase V1 G3 subunit (kidney isoform)
  7. CLCN7 — lysosomal Cl-/H+ antiporter (ClC-7), partners V-ATPase in acidification

Mitochondrial proteostasis

  1. CLPX — mitochondrial ClpXP AAA+ unfoldase/protease subunit

Cytosolic chaperone / co-chaperone

  1. CDC37L1 — Cdc37-like HSP90 co-chaperone (Cdc37 paralog)

ER proteostasis — folding, lectin chaperones, PPIases, collagen biogenesis

  1. CLGN — calmegin, testis-specific calnexin paralog (ER lectin chaperone)
  2. CALR3 — calreticulin-3, testis ER chaperone (calreticulin paralog)
  3. CNPY3 — canopy-3, ER co-chaperone for Toll-like receptor folding
  4. CRTAP — cartilage-associated protein, prolyl 3-hydroxylase complex chaperone
  5. CYB5R4 — NADH-cytochrome b5 reductase 4 (cyb5/heme; ER redox)
  6. COLGALT1 — collagen beta(1-O)galactosyltransferase 1 (ER, collagen glycosylation)
  7. COLGALT2 — collagen beta(1-O)galactosyltransferase 2
  8. CWC27 — spliceosome-associated cyclophilin/PPIase (proline isomerase)

Cytonuclear / nuclear proteostasis — histone chaperones

  1. CHAF1A — CAF-1 large subunit (histone H3-H4 chaperone)
  2. CHAF1B — CAF-1 p60 subunit (histone H3-H4 chaperone)

Ubiquitin-proteasome system — CRL substrate receptors, adaptors, E3s

  1. CRBN — cereblon, CRL4 substrate receptor (thalidomide/IMiD target)
  2. COP1 (RFWD2) — RING E3 ubiquitin ligase
  3. DCAF10 — DDB1/CUL4-associated factor 10 (CRL4 substrate receptor)
  4. DCAF11 — DDB1/CUL4-associated factor 11 (CRL4 substrate receptor)
  5. CACUL1 — CDK2-associated cullin domain 1 (cullin regulator)
  6. CDK5RAP3 — CDK5RAP3 / C53, UFMylation pathway, ribosome/ER quality control
  7. CGRRF1 — cell growth regulator with RING finger 1 (ER membrane E3, ERAD)
  8. CNOT4 — CCR4-NOT complex RING E3 ligase (translation/RQC-linked)
  9. CHIC2 — cysteine-rich hydrophobic domain 2 (vesicle/UPS-adjacent)
  10. CSNK2B — casein kinase 2 beta regulatory subunit (PN regulation)
  11. CSNK1D — casein kinase 1 delta (PN regulation)

Method

For each gene:
- uv run ai-gene-review fetch-gene human <GENE> (UniProt, GOA, cached
publications, seeded -ai-review.yaml).
- Research from cached publications + UniProt + literature; notes recorded in
<GENE>-notes.md with provenance.
- Each seeded GOA annotation reviewed per GO guidelines (ACCEPT /
KEEP_AS_NON_CORE / MODIFY / MARK_AS_OVER_ANNOTATED / REMOVE / UNDECIDED) with
supported_by evidence.
- description, core_functions, suggested_questions, suggested_experiments
populated.
- Validated with uv run ai-gene-review validate ....