Diamond-Blackfan anemia 11

Summary

Diamond-Blackfan anemia 11 (MONDO:0013964) is a disease caused by RPL26 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RPL26 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 11
Mondo ID	MONDO:0013964
OMIM	614900
DOID	DOID:0111892
NCIT	C176920
UMLS	C3554042
MedGen	766956
GARD	0015879
Is cancer (heuristic)	no

Also known as: DBA11 · Diamond-Blackfan anaemia caused by mutation in RPL26 · Diamond-Blackfan Anaemia type 11 · Diamond-Blackfan anemia 11 · Diamond-Blackfan anemia caused by mutation in RPL26 · Diamond-Blackfan Anemia type 11 · RPL26 Diamond-Blackfan anaemia · RPL26 Diamond-Blackfan anemia

Data availability: 15 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › pure red-cell aplasia › Diamond-Blackfan anemia › Diamond-Blackfan anemia 11

Related subtypes (21): Diamond-Blackfan anemia 1, Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, Diamond-Blackfan anemia 2, Diamond-Blackfan anemia 15 with mandibulofacial dysostosis, Diamond-Blackfan anemia 3, Diamond-Blackfan anemia 4, Diamond-Blackfan anemia 5, Diamond-Blackfan anemia 6, Diamond-Blackfan anemia 7, Diamond-Blackfan anemia 8, Diamond-Blackfan anemia 9, Diamond-Blackfan anemia 10, Diamond-Blackfan anemia 12, Diamond-Blackfan anemia 13, Diamond-Blackfan anemia 21, Diamond-Blackfan anemia 18, Diamond-Blackfan anemia 19, Diamond-Blackfan anemia 20, Diamond-Blackfan anemia 16, Diamond-Blackfan anemia 17, Diamond-Blackfan anemia 22

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

15 retrieved; paginated sample, class counts are floors:

4 benign/likely benign, 3 pathogenic, 3 uncertain significance, 3 likely pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1339822	NM_000987.5(RPL26):c.341del (p.Asp114fs)	RPL26	Pathogenic	no assertion criteria provided
2627100	NM_000987.5(RPL26):c.87del (p.Met30fs)	RPL26	Pathogenic	criteria provided, single submitter
39740	NM_000987.5(RPL26):c.120_121del (p.Lys41fs)	RPL26	Pathogenic	criteria provided, single submitter
2627098	NM_000987.5(RPL26):c.-6+3_-6+25del	RPL26	Likely pathogenic	criteria provided, single submitter
2627099	NM_000987.5(RPL26):c.-5-2A>G	RPL26	Likely pathogenic	criteria provided, single submitter
4072391	NM_000987.5(RPL26):c.36_39del (p.Ser12fs)	RPL26	Likely pathogenic	criteria provided, single submitter
2500079	NM_000987.5(RPL26):c.168+6T>G	RPL26	Uncertain significance	criteria provided, single submitter
4278369	NM_000987.5(RPL26):c.168G>C (p.Gln56His)	RPL26	Uncertain significance	criteria provided, single submitter
945300	NM_000987.5(RPL26):c.377G>A (p.Arg126His)	RPL26	Uncertain significance	criteria provided, multiple submitters, no conflicts
1164657	NM_000987.5(RPL26):c.327A>G (p.Leu109=)	RPL26	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1634626	NM_000987.5(RPL26):c.168+17G>A	RPL26	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
3767087	NM_000987.5(RPL26):c.267G>A (p.Lys89=)	RPL26	Likely benign	criteria provided, multiple submitters, no conflicts
463369	NM_000987.5(RPL26):c.96C>T (p.Ser32=)	RPL26	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
514617	NM_000987.5(RPL26):c.-5-16_-5-15del	RPL26	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
704376	NM_000987.5(RPL26):c.342C>T (p.Asp114=)	RPL26	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RPL26	Strong	Autosomal dominant	Diamond-Blackfan anemia 11	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPL26	Orphanet:124	Diamond-Blackfan anemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL26	HGNC:10327	ENSG00000161970	P61254	Large ribosomal subunit protein uL24	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL26	Large ribosomal subunit protein uL24	Component of the large ribosomal subunit.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL26	Scaffold/PPI	no		Ribosomal_uL24_euk_arc, KOW, Ribosomal_uL24_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL26	134	ubiquitous	marker	cortical plate, calcaneal tendon, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL26	4,651

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL26	P61254	197

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Peptide chain elongation	1	126.9×	0.012	RPL26
Viral mRNA Translation	1	126.9×	0.012	RPL26
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	125.5×	0.012	RPL26
Selenocysteine synthesis	1	120.2×	0.012	RPL26
Eukaryotic Translation Termination	1	120.2×	0.012	RPL26
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	117.7×	0.012	RPL26
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.012	RPL26
Formation of a pool of free 40S subunits	1	112.0×	0.012	RPL26
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	110.9×	0.012	RPL26
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	1	106.7×	0.012	RPL26
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.012	RPL26
SRP-dependent cotranslational protein targeting to membrane	1	100.2×	0.012	RPL26
GTP hydrolysis and joining of the 60S ribosomal subunit	1	100.2×	0.012	RPL26
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1	97.6×	0.012	RPL26
Regulation of expression of SLITs and ROBOs	1	69.2×	0.015	RPL26
Major pathway of rRNA processing in the nucleolus and cytosol	1	61.7×	0.016	RPL26

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of translation involved in cellular response to UV	1	16852.0×	7e-04	RPL26
positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	8426.0×	7e-04	RPL26
positive regulation of DNA damage response, signal transduction by p53 class mediator	1	991.3×	0.004	RPL26
cellular response to gamma radiation	1	601.9×	0.005	RPL26
ribosomal large subunit biogenesis	1	443.5×	0.005	RPL26
DNA damage response, signal transduction by p53 class mediator	1	358.6×	0.005	RPL26
cellular response to UV	1	295.6×	0.005	RPL26
positive regulation of translation	1	227.7×	0.006	RPL26
cytoplasmic translation	1	185.2×	0.007	RPL26
rRNA processing	1	141.6×	0.008	RPL26
translation	1	102.8×	0.010	RPL26

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RPL26	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPL26	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL26

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RPL26	90	Binding:90

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
GENTAMICIN SULFATE	4	RPL26

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPL26
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.