Hypochlorous Acid Metabolic Process Terms — Obsoletion

IN_PROGRESS OBSOLETION

Species: mouse

Genes: Mpo

Hypochlorous Acid Metabolic Process Terms — Obsoletion

Bottom line: GO has obsoleted all three hypochlorous acid (HOCl)
process terms — the grouping term GO:0002148 first, then the biosynthetic
(GO:0002149) and catabolic (GO:0002150) terms — with the obsolete records
giving the reason "this BP term represents a MF term"; the originating ticket
(go-ontology#22891) had instead flagged the wrong is_a parent (see Overview).
The affected annotation was a single MGI IMP on mouse Mpo (PMID:10085024), plus
a rat ISO copy. Both are already gone: a fresh just fetch-gene mouse Mpo
returns 85 GOA rows (84 distinct annotations) with no GO:0002149, and QuickGO returns 65 rat Mpo rows
with none to GO:0002149, so the migration landed upstream and the rat row
followed the mouse one as predicted. Mouse Mpo is now fully reviewed here
(genes/mouse/Mpo/), which closes the deferred-review item and settles the MF
question: GO has no term for the myeloperoxidase reaction
(chloride + H2O2 + H+ = hypochlorous acid + H2O, EC 1.11.2.2, RHEA:28218 —
not RHEA:43232, which is isatin hydrolase), and the review therefore accepts
GO:0004601 peroxidase activity — which carries "myeloperoxidase activity" as a
narrow synonym and the Reactome xref for MPO-dependent HOCl production — while
proposing a child term for the reaction itself (hypochlorous acid synthase
activity, named so as not to read as a child of GO:0016691). GO:0016691 is organic
chlorination and GO:0140825 is lactoperoxidase activity, as suspected.
Remaining work is upstream (create the MF term) or optional (a human MPO review).

Overview

A GO obsoletion proposal targets three biological-process terms in the
hypochlorous acid (HOCl) branch:

The two rationales come from different stages. The originating ticket,
go-ontology#22891, argued that the original parentage
(is_a organic acid metabolic process, GO:0006082) is incorrect because
hypochlorous acid contains no carbon and so is not an organic acid. The
grouping-term obsoletion at the parent level (go-ontology#30524) removed
GO:0002148, which had no remaining annotations. GO has since obsoleted the
two child terms too; their obsolete definitions record a different final
reason, "The reason for obsoletion is that this BP term represents a MF
term" (QuickGO, GO:0002149/GO:0002150, rechecked 2026-10-16). The MGI mouse
Mpo row has since left GO:0002149 in the GOA download, and the rat ISO copy
with it, so the AI Gene Review action — review Mpo against the MF and
host-defence context together — has now been carried out.

This project tracks the impact on AI Gene Review. Mouse Mpo is reviewed as
of 2026-10-16.

Upstream tickets

Annotation inventory (verified via QuickGO 2026-05-20)

Aspect Term Gene UniProt Taxon Evidence Reference Assigned by Qualifier
BP GO:0002149 hypochlorous acid biosynthetic process Mpo P11247 NCBITaxon:10090 (mouse) IMP PMID:10085024 MGI acts_upstream_of_or_within
BP GO:0002149 hypochlorous acid biosynthetic process Mpo A0A0G2K1A2 NCBITaxon:10116 (rat) ISO (ECO:0000266) GO_REF:0000121 RGD acts_upstream_of_or_within (with-from MGI:97137 = mouse Mpo)
BP GO:0002150 hypochlorous acid catabolic process — — — — — — (no direct protein annotations returned by QuickGO)

The rat annotation is ISO-propagated from the mouse one; if the mouse
annotation is migrated, the rat record will follow automatically through
the next ISO pipeline. The catabolic-process term (GO:0002150) appears to
have no direct protein annotations, so its obsoletion is purely
terminological.

Why this fits AI Gene Review

Single concrete gene: mouse myeloperoxidase (Mpo, P11247). Myeloperoxidase
is the textbook HOCl-generating enzyme of neutrophils (RHEA:43232,
EC 1.11.2.2; H2O2 + Cl- + H+ → HOCl + H2O). The enzyme catalyzes one well-defined reaction whose product is HOCl.
An earlier draft of this page named GO:0140825 as the precise MF term
for it, but OLS labels GO:0140825 lactoperoxidase activity ("2 a phenolic
donor + H2O2 = 2 a phenolic radical donor + 2 H2O"), which is not the
HOCl-forming reaction. The nearest GO term found by name,
GO:0016691 chloride peroxidase activity, is defined as organic
chlorination ("2 R-H + 2 chloride + H2O2 = 2 R-Cl + 2 H2O").

Resolved 2026-10-16. Two corrections and one conclusion:

  1. The reaction identifier used earlier on this page and in issue #4098,
    RHEA:43232, is wrong: it is isatin + H2O = isatinate + H(+). The
    myeloperoxidase reaction is RHEA:28218, which is what UniProt P11247
    itself cites ("Reaction=chloride + H2O2 + H(+) = hypochlorous acid + H2O;
    Xref=Rhea:RHEA:28218 … EC=1.11.2.2").
  2. Searching GO for RHEA:28218 and EC:1.11.2.2 (QuickGO term search plus an
    xref scan of the local ontology build) returns no term. GO:0016691 is
    EC:1.11.1.10 (organic chlorination) and GO:0140825 is EC:1.11.1.7; the only
    other live HOCl-named terms are GO:1901531 hypochlorite binding and
    GO:1901530 response to hypochlorite, neither catalytic.

  3. GO currently files this activity under GO:0004601 peroxidase activity,
    which carries myeloperoxidase activity as a narrow synonym and the
    Reactome xrefs R-HSA-6789126 / R-HSA-6789031 ("Myeloperoxidase (MPO)
    produces hypochlorous acid (HOCl)"). The Mpo review therefore accepts
    GO:0004601 as the most precise existing term and proposes a child,
    hypochlorous acid synthase activity (skos:exactMatch RHEA:28218) - named to
    avoid reading as a child of GO:0016691 - modelled on the sibling term GO:0036393
    thiocyanate peroxidase activity (RHEA:69416), which already exists for the
    pseudohalide version of the same reaction and is annotated to Mpo by the Rhea
    pipeline. Creating the term is an upstream GO request.
    The cached human neutrophil extracellular trap GO-CAM 68fac5ed00000028
    already models human MPO as GO:0004601 peroxidase activity with H2O2 input
    and HOCl output, which reinforces the GO-CAM/MF shape of the assertion
    while leaving the need for a precise HOCl-forming MF term unresolved.
    The GOA update is therefore a clean Type B refresh:

  4. Migrate the IMP annotation away from the now-obsolete BP term to
    whichever target the upstream ticket settles on.

  5. Most likely target classes the curators are choosing between are:
  6. GO:0042744 hydrogen peroxide catabolic process (since Mpo consumes H2O2),
  7. a broader ROS-biosynthesis term such as
    GO:1903409 reactive oxygen species biosynthetic process,
  8. or a new term hypochlorous acid biosynthesis from hydrogen peroxide
    if upstream chooses to keep the chemistry and only fix the parentage.

Note: GO:0042554 superoxide anion generation is not a defensible
target for Mpo — that term is the NADPH-oxidase (NOX2/CYBB) step
upstream of Mpo in the respiratory burst (NADPH oxidase → O2•- → SOD
→ H2O2 → Mpo → HOCl); Mpo consumes H2O2 rather than generating
superoxide.

The upstream go-annotation#6404 body does not list a chosen replacement,
so this remains passive tracking until the upstream decision lands.

Impact on this repo

Genes in scope

Tier Gene Organism UniProt Reviewed here? Status
1 Mpo (myeloperoxidase) Mus musculus P11247 Yes (2026-10-16) The only gene that had a direct IMP to GO:0002149. Full review of all 84 distinct GOA annotations (85 TSV rows, one duplicated); HOCl chemistry retained as MF + H2O2 catabolism; a child of GO:0004601 proposed for the reaction.
(follow-on) Mpo Rattus norvegicus A0A0G2K1A2 No ISO descendant; verified in QuickGO this session to carry no GO:0002149 row, so it followed the mouse migration. No residual RGD follow-up.
(follow-on) MPO Homo sapiens P05164 No Human ortholog; optional review, not required by the obsoletion.

Remaining work

  1. Upstream GO ontology request — create a molecular-function child of
    GO:0004601 for chloride + H2O2 + H(+) = hypochlorous acid + H2O
    (EC 1.11.2.2, RHEA:28218). The proposal text, with parentage and mapping,
    is in proposed_new_terms of the Mpo review. Not actionable in this repo.
  2. Upstream annotation ticket — geneontology/go-annotation#6404 can be
    closed once the MGI migration is confirmed on their side; the GOA download
    already shows the row gone. (That repository is not reachable from the
    session that made this change, so its comment state was not re-read.)
  3. Optional — review human MPO (P05164), which would also let the cached
    NET GO-CAM 68fac5ed00000028 be assessed against a gene review.

Priority

Low, and mostly finished. One experimental annotation was affected, it has
already migrated upstream, and the gene behind it is now reviewed. What is left
is an ontology request that only GO can act on, plus an optional human review.

Status