Diamond-Blackfan anemia 7

Summary

Diamond-Blackfan anemia 7 (MONDO:0012938) is a disease caused by RPL11 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RPL11 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 58

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 7
Mondo ID	MONDO:0012938
MeSH	C567254
OMIM	612562
DOID	DOID:0111878
NCIT	C176916
UMLS	C2675512
MedGen	436451
GARD	0015569
Is cancer (heuristic)	no

Also known as: DBA7 · Diamond-Blackfan anaemia caused by mutation in RPL11 · Diamond-Blackfan Anaemia type 7 · Diamond-Blackfan anemia 7 · Diamond-Blackfan anemia caused by mutation in RPL11 · Diamond-Blackfan Anemia type 7 · RPL11 Diamond-Blackfan anaemia · RPL11 Diamond-Blackfan anemia

Data availability: 58 ClinVar variants · 3 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 7

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 8, Diamond-Blackfan anemia 9, Diamond-Blackfan anemia 10, Diamond-Blackfan anemia 11, 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

58 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 12 conflicting classifications of pathogenicity, 11 pathogenic, 4 benign/likely benign, 3 benign, 3 likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1751021	NM_000975.5(RPL11):c.6+2T>C	LOC129929673	Pathogenic	criteria provided, multiple submitters, no conflicts
100640	NM_000975.5(RPL11):c.476_477del (p.Lys159fs)	RPL11	Pathogenic	no assertion criteria provided
100641	NM_000975.5(RPL11):c.204del (p.Ile68fs)	RPL11	Pathogenic	no assertion criteria provided
1705531	NM_000975.5(RPL11):c.124C>T (p.Gln42Ter)	RPL11	Pathogenic	criteria provided, single submitter
1708160	NM_000975.5(RPL11):c.94_97del (p.Asp31_Arg32insTer)	RPL11	Pathogenic	criteria provided, multiple submitters, no conflicts
2431941	NM_000975.5(RPL11):c.95_96del (p.Arg32fs)	RPL11	Pathogenic	criteria provided, single submitter
4077471	NM_000975.5(RPL11):c.18_25del (p.Lys8fs)	RPL11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
451147	NM_000975.5(RPL11):c.143_144del (p.Pro48fs)	RPL11	Pathogenic	criteria provided, multiple submitters, no conflicts
522687	NM_000975.5(RPL11):c.43_49del (p.Leu15fs)	RPL11	Pathogenic	criteria provided, single submitter
5751	NM_000975.5(RPL11):c.223C>T (p.Arg75Ter)	RPL11	Pathogenic	criteria provided, multiple submitters, no conflicts
5752	NM_000975.5(RPL11):c.60_61del (p.Cys21fs)	RPL11	Pathogenic	criteria provided, multiple submitters, no conflicts
5754	NM_000975.5(RPL11):c.158-1G>A	RPL11	Pathogenic	criteria provided, single submitter
992969	NM_000975.5(RPL11):c.465_466del (p.His155fs)	RPL11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1003082	NM_000975.5(RPL11):c.158-7C>G	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1745252	NM_000975.5(RPL11):c.508-9_508-5del	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1901070	NM_000975.5(RPL11):c.430AAG[1] (p.Lys145del)	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2435471	NM_000975.5(RPL11):c.238GAA[1] (p.Glu81del)	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2740977	NM_000975.5(RPL11):c.7-6T>G	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296818	NM_000975.5(RPL11):c.158-7C>T	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296820	NM_000975.5(RPL11):c.306T>C (p.Thr102=)	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3581893	NM_000975.5(RPL11):c.158-10C>A	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3581909	NM_000975.5(RPL11):c.264+18A>G	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
436550	NM_000975.5(RPL11):c.296_298del (p.Phe99del)	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
695512	NM_000975.5(RPL11):c.396+9A>G	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
875055	NM_000975.5(RPL11):c.264+9A>T	RPL11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296814	NM_000975.5(RPL11):c.-14T>C	LOC129929673	Uncertain significance	criteria provided, single submitter
3581866	NM_000975.5(RPL11):c.6+9C>G	LOC129929673	Uncertain significance	criteria provided, single submitter
1010860	NM_000975.5(RPL11):c.452T>C (p.Ile151Thr)	RPL11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1366485	NM_000975.5(RPL11):c.68A>G (p.Asn23Ser)	RPL11	Uncertain significance	criteria provided, multiple submitters, no conflicts
1736518	NM_000975.5(RPL11):c.396+3A>G	RPL11	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
RPL11	Definitive	Autosomal dominant	Diamond-Blackfan anemia 7	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPL11	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
RPL11	HGNC:10301	ENSG00000142676	P62913	Large ribosomal subunit protein uL5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL11	Large ribosomal subunit protein uL5	Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL11	Other/Unknown	no		Ribosomal_uL5, Ribosomal_uL5_CS, Ribosomal_uL5_dom_sf

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
cortical plate	1
ganglionic eminence	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL11	293	ubiquitous	marker	ganglionic eminence, cortical plate, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPL11	1,432

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL11	P62913	185

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	RPL11
Viral mRNA Translation	1	126.9×	0.012	RPL11
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	125.5×	0.012	RPL11
Selenocysteine synthesis	1	120.2×	0.012	RPL11
Eukaryotic Translation Termination	1	120.2×	0.012	RPL11
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	117.7×	0.012	RPL11
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.012	RPL11
Formation of a pool of free 40S subunits	1	112.0×	0.012	RPL11
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	110.9×	0.012	RPL11
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	1	106.7×	0.012	RPL11
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.012	RPL11
SRP-dependent cotranslational protein targeting to membrane	1	100.2×	0.012	RPL11
GTP hydrolysis and joining of the 60S ribosomal subunit	1	100.2×	0.012	RPL11
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	1	97.6×	0.012	RPL11
Regulation of expression of SLITs and ROBOs	1	69.2×	0.015	RPL11
Major pathway of rRNA processing in the nucleolus and cytosol	1	61.7×	0.016	RPL11

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
ribosomal large subunit assembly	1	1404.3×	0.004	RPL11
positive regulation of signal transduction by p53 class mediator	1	1203.7×	0.004	RPL11
negative regulation of ubiquitin-dependent protein catabolic process	1	842.6×	0.004	RPL11
ribosomal large subunit biogenesis	1	443.5×	0.004	RPL11
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	1	401.2×	0.004	RPL11
regulation of signal transduction by p53 class mediator	1	383.0×	0.004	RPL11
protein targeting	1	366.4×	0.004	RPL11
protein localization to nucleus	1	351.1×	0.004	RPL11
cytoplasmic translation	1	185.2×	0.007	RPL11
rRNA processing	1	141.6×	0.008	RPL11
translation	1	102.8×	0.010	RPL11

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
RPL11	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPL11	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPL11	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	RPL11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPL11
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.