Diamond-Blackfan anemia 3

Summary

Diamond-Blackfan anemia 3 (MONDO:0012529) is a disease caused by RPS24 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RPS24 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 3
Mondo ID	MONDO:0012529
MeSH	C536355
OMIM	610629
DOID	DOID:0111887
NCIT	C176912
UMLS	C1857719
MedGen	387892
GARD	0010241
Is cancer (heuristic)	no

Also known as: anaemia Diamond-Blackfan 3 · anemia Diamond-Blackfan 3 · DBA3 · Diamond-Blackfan anaemia caused by mutation in RPS24 · Diamond-Blackfan Anaemia type 3 · Diamond-Blackfan anemia 3 · Diamond-Blackfan anemia caused by mutation in RPS24 · Diamond-Blackfan Anemia type 3 · RPS24 Diamond-Blackfan anaemia · RPS24 Diamond-Blackfan anemia

Data availability: 69 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 3

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 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 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

69 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 12 benign, 8 benign/likely benign, 8 likely benign, 5 pathogenic, 4 conflicting classifications of pathogenicity, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
88977	NC_000010.11:g.78030403_78035536del	LOC130004144	Pathogenic	no assertion criteria provided
549764	NM_033022.4(RPS24):c.148A>C (p.Thr50Pro)	RPS24	Pathogenic	criteria provided, single submitter
7245	NM_033022.4(RPS24):c.316C>T (p.Gln106Ter)	RPS24	Pathogenic	no assertion criteria provided
7246	NM_033022.4(RPS24):c.46C>T (p.Arg16Ter)	RPS24	Pathogenic	criteria provided, multiple submitters, no conflicts
7247	NM_033022.4(RPS24):c.4_6delinsTACGGATAG (p.Asn2delinsTyrGlyTer)	RPS24	Pathogenic	no assertion criteria provided
4282505	NM_033022.4(RPS24):c.3G>C (p.Met1Ile)	LOC130004144	Likely pathogenic	criteria provided, single submitter
1162257	NM_033022.4(RPS24):c.157del (p.Asp53fs)	RPS24	Likely pathogenic	criteria provided, single submitter
2504586	NM_033022.4(RPS24):c.273del (p.Ala92fs)	RPS24	Likely pathogenic	criteria provided, single submitter
696301	NM_033022.4(RPS24):c.3+7C>T	LOC130004144	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1121639	NM_033022.4(RPS24):c.21C>T (p.Ile7=)	RPS24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1327106	NM_001142285.2(RPS24):c.799C>G (p.Pro267Ala)	RPS24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2762593	NM_033022.4(RPS24):c.348A>G (p.Lys116=)	RPS24	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1698829	NM_033022.4(RPS24):c.3G>A (p.Met1Ile)	LOC130004144	Uncertain significance	criteria provided, single submitter
301087	NM_033022.3(RPS24):c.-142A>G	LOC130004144	Uncertain significance	criteria provided, single submitter
3598084	NM_033022.4(RPS24):c.-8T>A	LOC130004144	Uncertain significance	criteria provided, single submitter
3598092	NM_033022.4(RPS24):c.-4C>G	LOC130004144	Uncertain significance	criteria provided, single submitter
877451	NM_033022.3(RPS24):c.-47T>G	LOC130004144	Uncertain significance	criteria provided, single submitter
1013633	NM_033022.4(RPS24):c.122G>A (p.Arg41Gln)	RPS24	Uncertain significance	criteria provided, multiple submitters, no conflicts
1048968	NM_001142285.2(RPS24):c.526G>A (p.Val176Met)	RPS24	Uncertain significance	criteria provided, single submitter
1414909	NM_033022.4(RPS24):c.23G>A (p.Arg8His)	RPS24	Uncertain significance	criteria provided, multiple submitters, no conflicts
1442613	NM_033022.4(RPS24):c.390+3dup	RPS24	Uncertain significance	criteria provided, multiple submitters, no conflicts
2418834	NM_033022.4(RPS24):c.4-3C>T	RPS24	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435480	NM_033022.4(RPS24):c.149C>G (p.Thr50Ser)	RPS24	Uncertain significance	criteria provided, single submitter
2441880	NM_001142285.2(RPS24):c.522del (p.Pro173_Trp174insTer)	RPS24	Uncertain significance	criteria provided, single submitter
2585257	NM_033022.4(RPS24):c.155C>T (p.Pro52Leu)	RPS24	Uncertain significance	criteria provided, single submitter
2689885	NM_033022.4(RPS24):c.390+4T>C	RPS24	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598100	NM_033022.4(RPS24):c.11C>T (p.Thr4Ile)	RPS24	Uncertain significance	criteria provided, single submitter
3598115	NM_033022.4(RPS24):c.220A>G (p.Met74Val)	RPS24	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598123	NM_033022.4(RPS24):c.248A>G (p.Lys83Arg)	RPS24	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598130	NM_033022.4(RPS24):c.260C>T (p.Pro87Leu)	RPS24	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
RPS24	Definitive	Unknown	Diamond-Blackfan anemia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS24	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
RPS24	HGNC:10411	ENSG00000138326	P62847	Small ribosomal subunit protein eS24	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS24	Small ribosomal subunit protein eS24	Component of the small ribosomal subunit.

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)
RPS24	Other/Unknown	no		Ribosomal_eS24, Ribosomal_uL23/eL15/eS24_sf, Ribosomal_eS24_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
colonic mucosa	1
ganglionic eminence	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS24	288	ubiquitous	marker	ganglionic eminence, mucosa of sigmoid colon, colonic mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPS24	974

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS24	P62847	214

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. 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
Eukaryotic Translation Initiation	1	308.6×	0.016	RPS24
Cap-dependent Translation Initiation	1	308.6×	0.016	RPS24
SARS-CoV-1 modulates host translation machinery	1	308.6×	0.016	RPS24
Eukaryotic Translation Elongation	1	278.5×	0.016	RPS24
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1	271.9×	0.016	RPS24
Nonsense-Mediated Decay (NMD)	1	233.1×	0.016	RPS24
SARS-CoV-2 modulates host translation machinery	1	223.9×	0.016	RPS24
Influenza Viral RNA Transcription and Replication	1	215.5×	0.016	RPS24
Formation of the ternary complex, and subsequently, the 43S complex	1	215.5×	0.016	RPS24
Selenoamino acid metabolism	1	196.9×	0.016	RPS24
Translation initiation complex formation	1	190.3×	0.016	RPS24
Ribosomal scanning and start codon recognition	1	190.3×	0.016	RPS24
Influenza Infection	1	175.7×	0.016	RPS24
SARS-CoV-1-host interactions	1	175.7×	0.016	RPS24
Cellular response to starvation	1	165.5×	0.016	RPS24
rRNA processing in the nucleus and cytosol	1	160.8×	0.016	RPS24
rRNA processing	1	146.4×	0.016	RPS24
SARS-CoV-1 Infection	1	142.8×	0.016	RPS24
Peptide chain elongation	1	126.9×	0.016	RPS24
Viral mRNA Translation	1	126.9×	0.016	RPS24
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	125.5×	0.016	RPS24
Signaling by ROBO receptors	1	124.1×	0.016	RPS24
Selenocysteine synthesis	1	120.2×	0.016	RPS24
Eukaryotic Translation Termination	1	120.2×	0.016	RPS24
SARS-CoV-2-host interactions	1	119.0×	0.016	RPS24
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	117.7×	0.016	RPS24
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.016	RPS24
Formation of a pool of free 40S subunits	1	112.0×	0.016	RPS24
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	110.9×	0.016	RPS24
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.016	RPS24

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
erythrocyte homeostasis	1	1296.3×	0.004	RPS24
ribosomal small subunit biogenesis	1	227.7×	0.009	RPS24
cytoplasmic translation	1	185.2×	0.009	RPS24
rRNA processing	1	141.6×	0.009	RPS24
translation	1	102.8×	0.010	RPS24

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
RPS24	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS24	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS24

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPS24	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	RPS24

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPS24
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.