Diamond-Blackfan anemia 10

Summary

Diamond-Blackfan anemia 10 (MONDO:0013217) is a disease caused by RPS26 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: RPS26 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 154

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 10
Mondo ID	MONDO:0013217
MeSH	C567649
OMIM	613309
DOID	DOID:0111888
NCIT	C176919
UMLS	C2750080
MedGen	412873
GARD	0015645
Is cancer (heuristic)	no

Also known as: DBA10 · Diamond-Blackfan anaemia caused by mutation in RPS26 · Diamond-Blackfan Anaemia type 10 · Diamond-Blackfan anemia 10 · Diamond-Blackfan anemia caused by mutation in RPS26 · Diamond-Blackfan Anemia type 10 · RPS26 Diamond-Blackfan anaemia · RPS26 Diamond-Blackfan anemia

Data availability: 154 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 10

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 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

154 retrieved; paginated sample, class counts are floors:

68 likely benign, 48 uncertain significance, 20 pathogenic, 5 benign, 4 likely pathogenic, 4 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2423490	NC_000012.11:g.(?56396006)(56437938_?)del	IKZF4	Pathogenic	criteria provided, single submitter
88979	NC_000012.10:g.54711095_54731551del	IKZF4	Pathogenic	no assertion criteria provided
1076796	NM_001029.5(RPS26):c.9_12del (p.Lys4fs)	RPS26	Pathogenic	criteria provided, multiple submitters, no conflicts
1356399	NM_001029.5(RPS26):c.73_76del (p.Asn25fs)	RPS26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1798678	NM_001029.5(RPS26):c.2T>C (p.Met1Thr)	RPS26	Pathogenic	criteria provided, multiple submitters, no conflicts
1798687	NM_001029.5(RPS26):c.3+1G>T	RPS26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
187849	NM_001029.5(RPS26):c.259C>T (p.Arg87Ter)	RPS26	Pathogenic	criteria provided, multiple submitters, no conflicts
187850	NM_001029.5(RPS26):c.4-2A>T	RPS26	Pathogenic	criteria provided, single submitter
2027475	NM_001029.5(RPS26):c.78_79del (p.Ala27fs)	RPS26	Pathogenic	criteria provided, single submitter
212066	NM_001029.5(RPS26):c.55C>T (p.Gln19Ter)	RPS26	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2697519	NM_001029.5(RPS26):c.4-1_6del	RPS26	Pathogenic	criteria provided, single submitter
3358915	NM_001029.5(RPS26):c.82C>T (p.Arg28Ter)	RPS26	Pathogenic	criteria provided, multiple submitters, no conflicts
3643952	NM_001029.5(RPS26):c.17_20del (p.Arg6fs)	RPS26	Pathogenic	criteria provided, single submitter
3721946	NM_001029.5(RPS26):c.103del (p.Ala35fs)	RPS26	Pathogenic	criteria provided, single submitter
470476	NM_001029.5(RPS26):c.224_225del (p.Val75fs)	RPS26	Pathogenic	criteria provided, multiple submitters, no conflicts
6122	NM_001029.5(RPS26):c.1A>G (p.Met1Val)	RPS26	Pathogenic	criteria provided, multiple submitters, no conflicts
6123	NM_001029.5(RPS26):c.1A>T (p.Met1Leu)	RPS26	Pathogenic	criteria provided, multiple submitters, no conflicts
6124	NM_001029.5(RPS26):c.97G>A (p.Asp33Asn)	RPS26	Pathogenic	no assertion criteria provided
6125	NM_001029.5(RPS26):c.31dup (p.Ala11fs)	RPS26	Pathogenic	no assertion criteria provided
6126	NM_001029.5(RPS26):c.3+1G>A	RPS26	Pathogenic	no assertion criteria provided
929406	NM_001029.5(RPS26):c.181+1del	RPS26	Pathogenic	no assertion criteria provided
933891	NM_001029.5(RPS26):c.2T>G (p.Met1Arg)	RPS26	Pathogenic	criteria provided, single submitter
934123	NM_001029.5(RPS26):c.196A>T (p.Lys66Ter)	RPS26	Pathogenic	criteria provided, single submitter
1325016	NM_001029.5(RPS26):c.3+2T>G	RPS26	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2433019	NM_001029.5(RPS26):c.181+1G>A	RPS26	Likely pathogenic	criteria provided, single submitter
2690689	NM_001029.5(RPS26):c.2T>A (p.Met1Lys)	RPS26	Likely pathogenic	criteria provided, single submitter
4077475	NM_001029.5(RPS26):c.182-1G>C	RPS26	Likely pathogenic	criteria provided, single submitter
1337471	NM_001029.5(RPS26):c.42C>T (p.Gly14=)	RPS26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1664629	NM_001029.5(RPS26):c.4-4G>T	RPS26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2435481	NM_001029.5(RPS26):c.344T>C (p.Met115Thr)	RPS26	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
RPS26	Definitive	Autosomal dominant	Diamond-Blackfan anemia 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS26	Orphanet:124	Diamond-Blackfan anemia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPS26	HGNC:10414	ENSG00000197728	P62854	Small ribosomal subunit protein eS26	gencc,clinvar
IKZF4	HGNC:13179	ENSG00000123411	Q9H2S9	Zinc finger protein Eos	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS26	Small ribosomal subunit protein eS26	Component of the small ribosomal subunit.
IKZF4	Zinc finger protein Eos	DNA-binding protein that binds to the 5’GGGAATRCC-3’ Ikaros-binding sequence.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS26	Other/Unknown	no		Ribosomal_eS26, Ribosomal_eS26_sf, Ribosomal_eS26_CS
IKZF4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
left adrenal gland cortex	1
mucosa of transverse colon	1
adrenal cortex	1
buccal mucosa cell	1
left adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS26	140	ubiquitous	marker	granulocyte, left adrenal gland cortex, mucosa of transverse colon
IKZF4	242	ubiquitous	marker	buccal mucosa cell, left adrenal gland, adrenal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IKZF4	1,011
RPS26	829

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS26	P62854	190
IKZF4	Q9H2S9	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. Enrichment computed across 2 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	RPS26
Cap-dependent Translation Initiation	1	308.6×	0.016	RPS26
SARS-CoV-1 modulates host translation machinery	1	308.6×	0.016	RPS26
Eukaryotic Translation Elongation	1	278.5×	0.016	RPS26
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1	271.9×	0.016	RPS26
Nonsense-Mediated Decay (NMD)	1	233.1×	0.016	RPS26
SARS-CoV-2 modulates host translation machinery	1	223.9×	0.016	RPS26
Influenza Viral RNA Transcription and Replication	1	215.5×	0.016	RPS26
Formation of the ternary complex, and subsequently, the 43S complex	1	215.5×	0.016	RPS26
Selenoamino acid metabolism	1	196.9×	0.016	RPS26
Translation initiation complex formation	1	190.3×	0.016	RPS26
Ribosomal scanning and start codon recognition	1	190.3×	0.016	RPS26
Influenza Infection	1	175.7×	0.016	RPS26
SARS-CoV-1-host interactions	1	175.7×	0.016	RPS26
Cellular response to starvation	1	165.5×	0.016	RPS26
rRNA processing in the nucleus and cytosol	1	160.8×	0.016	RPS26
rRNA processing	1	146.4×	0.016	RPS26
SARS-CoV-1 Infection	1	142.8×	0.016	RPS26
Peptide chain elongation	1	126.9×	0.016	RPS26
Viral mRNA Translation	1	126.9×	0.016	RPS26
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	125.5×	0.016	RPS26
Signaling by ROBO receptors	1	124.1×	0.016	RPS26
Selenocysteine synthesis	1	120.2×	0.016	RPS26
Eukaryotic Translation Termination	1	120.2×	0.016	RPS26
SARS-CoV-2-host interactions	1	119.0×	0.016	RPS26
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	117.7×	0.016	RPS26
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.016	RPS26
Formation of a pool of free 40S subunits	1	112.0×	0.016	RPS26
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	110.9×	0.016	RPS26
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.016	RPS26

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of RNA splicing	1	1203.7×	0.006	RPS26
cytoplasmic translation	1	92.6×	0.034	RPS26
protein homooligomerization	1	61.1×	0.034	IKZF4
translation	1	51.4×	0.034	RPS26
negative regulation of DNA-templated transcription	1	15.8×	0.087	IKZF4
positive regulation of transcription by RNA polymerase II	1	7.4×	0.152	IKZF4
regulation of transcription by RNA polymerase II	1	5.8×	0.164	IKZF4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
RPS26	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS26	1	4
IKZF4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS26

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPS26	89	Binding:89

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	RPS26

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPS26
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	1	IKZF4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
IKZF4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.