[edkerk]

Adds PXMP2 (ENSG00000176894), the channel-forming protein of the peroxisomal membrane. It forms a non-selective pore for solutes up to about 300–600 Da (PMID:19352492).

PXMP2 is now the GPR of 40 cytosol–peroxisome transports that had no gene. These are uniports of water-soluble metabolites up to 300 Da: organic acids (glycolate, glyoxylate, oxalate, lactate, AKG, malate, OAA, succinate, isocitrate, dicarboxylic acids), amino acids, purines (urate, xanthine, hypoxanthine), Pi, PPi, DHAP, glycerol-3-phosphate, IPP and polyamines.

Not included:

• gases, water and H2O2, which cross membranes without PXMP2 (PMID:31129117);
• H+, Na+ and NH4+;
• lipophilic compounds;
• O-propanoylcarnitine;
• anything above 300 Da.

This lets ftINIT keep these transports wherever PXMP2 is expressed. A PXMP2 knockout does not change growth in the full model.

[github-actions]

Model quality report

⚠️ 6 pre-existing finding(s), no regressions vs develop. Non-blocking. Gates: duplicate keys 0 ✅, growth 1.9 ✅.

Section	Status
Model & network checks (18)	⚠️ 6 pre-existing
Model file & metabolic tasks (5)	✅ all pass
MEMOTE	✅ 63.8% (core subset)
Full report	model_qc_summary.md

Pre-existing:

• Cross-refs inconsistent across compartments: 2
• Reactions flagged by MACAW dead-end test: 1142
• Reactions flagged as MACAW duplicates: 377
• Mass-imbalanced reactions: 71
• Charge-imbalanced reactions: 233
• Structure vs formula/charge inconsistencies: 316

✅ unchanged · ✨ improved vs develop · ⚠️ pre-existing, non-blocking · ❌ regression

Full workflow run · this comment is edited as results come in

[edkerk]

/run gene-essentiality

[github-actions]

🧬 Started gene-essentiality on feat/pxmp2-peroxisomal-pore (this takes a few hours). Track it in the Actions tab.

[github-actions]

Gene essentiality was run on this pull request via GH Actions.

Gene essentiality: effect of this change

Checked 1 gene(s) directly affected plus 871 more that share a metabolite with one of them.

A gene counts as changed below only if the flip agrees in direction across at least 3 of the 5 cell-line models; fewer than that is grouped as likely noise from ftINIT's run-to-run variability instead.

Category	Status
Growth effect changed (vs Hart 2015)	✅ 0
Other role changed (not Hart-comparable)	ℹ️ 1
Likely noise (<3/5 lines)	ℹ️ 17
No change	✅ 854

Full detail: gene-essential_summary.md.

✅ unchanged · ✨ correct vs Hart 2015 · ❌ wrong vs Hart 2015 · ℹ️ not comparable to Hart 2015

The unscoped, every-gene matrix behind the table above is committed to gene-essential.csv.

Note: in the case of multiple test runs, this post is edited.

[edkerk]

The reasoning and evidence for the PXMP2 GPRs added here are documented in #1111.

A correction in #1105: each of the 40 reactions now has the note "PXMP2 forms a non-selective pore in the peroxisomal membrane; Pxmp2-/- mice keep part of this permeability (PMID:19352492)". The channel activity was measured for mouse Pxmp2 (PMID 19352492), and Pxmp2 knockout mice only partly lose peroxisomal permeability, but the single-gene GPR makes all 40 transports depend on PXMP2 in a gene deletion. The note records this.