NBN / nibrin (O60934, 754 aa) - the MRN subunit whose loss causes a leukaemia-predisposition syndrome and yet is almost dispensable in DepMap: mean -0.047 against MRE11's -0.542 in the same complex, the same call and the same release

No three-dimensional model is available for this protein, so the map above is the whole picture. That is itself informative: AlphaFold does not model chains this long, and the parts that have been crystallised are held under the entries for the individual domains.

1. Which reconciliation of the NBN paradox is right - hypomorphic allele, MRE11-carried fitness, or a developmental rather than cell-autonomous mechanism? RAD50's Chronos profile would discriminate the second and was not fetched.
2. Is the lymphoid malignancy of Nijmegen breakage syndrome enriched for 11q23 rearrangement? The registries that would answer it exist and the question has not been asked in those words - the same shape as the open question already standing in gene-brca1 about therapy-related leukaemia.
3. Does the NBN absence survive a search on the retired symbol NBS1 and on the complex name? This entry's own bounded absence is knowingly incomplete on both counts and should not be quoted as a bound until they are run.

1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

   Nibrin is a double-strand-break repair protein mutated in Nijmegen breakage syndrome, an autosomal recessive chromosomal-instability disorder whose phenotype includes marked predisposition to lymphoid malignancy.

   Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. · Varon R, et al. · Cell 1998
   PMID 9590180DOI
   ▸What this evidence cannot show

   The founding disease-gene paper. It establishes the gene-disease link and the repair role; the malignancy-incidence figures quoted in this field come from later registry series that were not fetched here, so this entry states the predisposition qualitatively and quotes no rate.

   ▸Evidence that argues against this (1)

   • Nijmegen breakage syndrome predisposes to lymphoma and lymphoid leukaemia broadly; nothing in this literature connects it to KMT2A rearrangement specifically, and a predisposition gene for a lineage is not evidence about a locus. The DepMap profile (-0.047) additionally shows that whatever the mechanism of predisposition is, it is not a cell-autonomous fitness requirement in established lines. Broad Institute DepMap / Open Targets Platform 2026
2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

   NBN has a mean DepMap Chronos gene effect of -0.047 across 1,258 lines with 1.3% below -0.5, eleven-fold shallower than MRE11 (-0.542, 56.1%) which is a subunit of the same MRN complex, both fetched in one call against Open Targets dataVersion 26.06.

   DepMap CRISPR gene-effect (Chronos) for NBN, served by the Open Targets Platform GraphQL API · Broad Institute DepMap / Open Targets Platform · Open Targets Platform 26.06 (meta.dataVersion year 26 month 06), fetched 2026-09-22 2026
   ▸What this evidence cannot show

   Rule 83: no DepMap release id in the payload, so the Open Targets dataVersion is recorded; screen counts are gene-specific. Rule 84: no median-split proportion. A flat Chronos score in cancer lines is not evidence that NBN is dispensable in a normal cell, in development, or in the immune system - and the human syndrome shows it is not.

   ▸Evidence that argues against this (1)

   • A near-zero mean gene effect can also mean the screen failed for that gene - poor guide performance, low expression, or a short half-life protein whose knockout is incomplete over the screen window. This entry treats the flat score as a real observation only because it is internally consistent across 1,258 lines and because the live low-screen control (OR4F5, 5 screens) shows the endpoint reports sparse data as sparse rather than as zero. Broad Institute DepMap / Open Targets Platform 2026

• ← refutes`absence_class` is one token per ENTRY while the entries carry seven to eleven distinct gaps each, so it is a summary label - and inside gene-nbn it hid a verifiably false ENCODE claim for three cycles

  two fields of gene-nbn asserted no released ENCODE TF ChIP-seq experiment for NBN; four exist (ENCSR278SQL, ENCSR210ZYL, ENCSR591EBL, ENCSR085QEV), verified live on both endpoints

• ← related toI audited whether a valid absence token is the RIGHT token, expecting the gene-nbn error to be widespread. It is not: 3 of 4 read were correctly scoped, the scoping is done in prose, and 39 of 40 flagged entries carry no machine-readable scope

  the one token found wrong, and its error was a false factual claim inside a field rather than a mis-scoped class

• ← part ofMRE11 (P49959, 708 aa) - the nuclease that makes the first cut of end resection, named in 10 entries of this graph and never written; DepMap mean -0.542 with 56% of 1,258 lines below -0.5, the deepest dependency in the whole resection cascade

  both subunits of the MRN complex - and eleven-fold apart in DepMap

• part of →MRE11 (P49959, 708 aa) - the nuclease that makes the first cut of end resection, named in 10 entries of this graph and never written; DepMap mean -0.542 with 56% of 1,258 lines below -0.5, the deepest dependency in the whole resection cascade

  MRN complex; NBN is the ATM-recruiting scaffold

• part of →What is left of the resection absence after the compute was done: the resting state is now MEASURED and negative in 13 ENCODE datasets, so the whole question collapses onto the DAMAGE state, which is never-measured for all six proteins in every cell type on Earth

  never-measured at this locus in any cell type

• ← refutesOutside ENCODE the resection layer is not one absence but four: 31 BRCA1, 45 CBX3, 22 KDM5A, 14 MRE11 and 8 CtIP ChIP-seq experiments exist in ChIP-Atlas, DNA2 and RAD50 have one each, and only BARD1 and EXO1 have none in any of the three archives

  gene-nbn states 'no ENCODE ChIP-seq experiment exists'; NBN has four (ENCSR278SQL, ENCSR085QEV, ENCSR210ZYL, ENCSR591EBL)

• ← related toThe MRN asymmetry adjudicated: RAD50 -0.114 sits with NBN -0.047 and not with MRE11 -0.542, so it is not one subunit against two - and yet MRE11 and RAD50 covary across 1,208 cell lines at r = 0.554, the same as BRCA1 against BARD1, against a background of zero

  NBN is not the odd one out; RAD50 sits with it and the pair's correlation with MRE11 is pathway-level (0.28-0.32), not complex-level

• ← part ofRAD50 (Q92878, 1312 aa) - the third MRN subunit, and the one that settles whether the complex is incoherent in DepMap: mean -0.114 with 5.2% of 1,257 lines below -0.5, so it sits with NBN and not with MRE11, yet it covaries with MRE11 across cell lines as tightly as BRCA1 does with BARD1

  third subunit of MRE11-RAD50-NBS1