XAGE5: historical rescue and current antibody hold
Reviewed 24 October 2026 against OncoRef 1.19.1 and its pinned HPA v23 inputs.
XAGE5 (ENSG00000171405) remains Neither / Antibody in the current target
sets: Target = false; Forbidden = false. No gene-specific rescue or new
exclusion is introduced by this review.
What happened after PR #59
PR #59 left the one-gene
MANUALLY_EXPRESSED_CTA exception as an open question.
PR #60, merged on 12 June 2026,
resolved that question by replacing the XAGE5 exception with a general
low-expression rule. The historical expression accessors retain candidates with
MODERATE restriction confidence and STRICT reproductive RNA, subject to their
other nomination and observed-expression requirements. XAGE5 qualifies at
1.1 nTPM in testis, as do eligible peers with the same evidence signature.
That historical membership is not the current CTA/Unsafe/Neither decision.
cta.cta_gene_names() still includes XAGE5; target_sets.gene_names("CTA")
does not. The general rescue does not bypass the current admission or
normal-cell review rules. Use target_sets for current target and forbidden
sets, as described in the target-set guide.
Recorded expression
| Evidence | XAGE5 result | Interpretation |
|---|---|---|
| HPA v23 consensus bulk RNA | Testis 1.1 nTPM; all 49 other measured tissues 0 nTPM | Low reproductive RNA; reported zeros are source measurements |
| Maximum audited non-permitted RNA, TPM sources | 2.2666887504 TPM | Below the hard >30 TPM exclusion |
| Maximum audited non-permitted RNA, nTPM sources | 0.4 nTPM | Below the hard >30 nTPM exclusion |
| Curated HPA normal-tissue IHC | No records | Missing coverage, not negative staining |
| Primary antibody HPA052507 | 78 tissue/cell records; profile and antibody validation both Uncertain | Cannot supply reliable reproductive protein admission evidence |
| Primary staining in Vital/Protected/Manageable compartments | 12 positive records among 48 assessed records | Triggers the existing uncertain-antibody review rule |
The RNA maxima keep TPM and nTPM separate. They summarize the measured contexts; they do not establish absence in every normal cell or donor. The IHC counts are antibody/tissue/cell aggregates, not donor-positive fractions.
All 12 non-permitted positive primary records use HPA052507:
| Tissue | Cells | Staining |
|---|---|---|
| Caudate | Neuronal cells | Medium |
| Cerebral cortex | Neuronal cells | Medium |
| Hippocampus | Neuronal cells | Low |
| Duodenum | Glandular cells | Medium |
| Small intestine | Glandular cells | Medium |
| Liver | Hepatocytes | Low |
| Lung | Macrophages | Low |
| Lymph node | Non-germinal center cells | Medium |
| Pancreas | Exocrine glandular cells | Medium |
| Stomach 1 | Glandular cells | Low |
| Stomach 2 | Glandular cells | Low |
| Thyroid gland | Glandular cells | Medium |
The same uncertain antibody reports Low staining in testicular seminiferous ducts and High staining in placental trophoblasts. Those findings do not validate the antibody's specificity or resolve its normal-tissue staining.
Sources: the pinned HPA v23 bulk RNA archive, curated IHC archive, and primary antibody XML archive. The reproducible extracted observations are in the primary-antibody table and RNA context table. The current gene table records the decision and evidence flags.
Why it remains Neither
The current screen has two unresolved requirements for XAGE5:
- Its 1.1 nTPM reproductive bulk RNA is below the 5 nTPM admission floor. The reviewed evidence table currently supplies neither reliable positive reproductive protein nor the affirmative reproductive-plus-tumor evidence needed to bypass that floor. Published RNA nominations remain in intake; this is not a claim that XAGE5 lacks cancer literature.
- Positive normal staining from an Uncertain antibody independently requires review. Even sufficient reproductive/tumor admission evidence would not remove that hold.
The current Cell RNA, Immune RNA and Corneal RNA review flags are false. No audited non-permitted RNA value exceeds 30 TPM or nTPM. The unresolved staining therefore supports Neither / Antibody, without asserting confirmed normal protein production, clinical toxicity or inclusion in forbidden proteins.
Evidence needed for reconsideration
The open question is whether HPA052507's neuronal and other normal staining is specific to XAGE5. Reconsideration needs independently supported protein identity in those compartments and reliable reproductive protein evidence or reviewed reproductive-plus-tumor evidence. Resolving only the low RNA admission floor would leave the normal-antibody hold in place. Any later evidence should be recorded with its assay, tissue, source and limitations and evaluated by the same rules used for other candidates.
from oncoref import cta, target_sets
assert "XAGE5" in cta.cta_gene_names() # Historical expression definition.
assert "XAGE5" not in target_sets.gene_names("CTA")
assert "XAGE5" in target_sets.gene_names("Neither")
assert "XAGE5" not in target_sets.gene_names("Unsafe")
row = target_sets.results().set_index("Gene").loc["XAGE5"]
assert row["Detail"] == "Antibody"
assert not row["Target"] and not row["Forbidden"]