Diamond-Blackfan anemia 9

Summary

Diamond-Blackfan anemia 9 (MONDO:0013216) is a disease caused by RPS10 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: RPS10 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 51

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 9
Mondo ID	MONDO:0013216
MeSH	C567650
OMIM	613308
DOID	DOID:0111884
NCIT	C176918
UMLS	C2750081
MedGen	412874
GARD	0015644
Is cancer (heuristic)	no

Also known as: DBA9 · Diamond-Blackfan anaemia caused by mutation in RPS10 · Diamond-Blackfan Anaemia type 9 · Diamond-Blackfan anemia 9 · Diamond-Blackfan anemia caused by mutation in RPS10 · Diamond-Blackfan Anemia type 9 · RPS10 Diamond-Blackfan anaemia · RPS10 Diamond-Blackfan anemia

Data availability: 51 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 9

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 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

51 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 7 benign/likely benign, 6 benign, 5 conflicting classifications of pathogenicity, 4 pathogenic, 2 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
6185	NM_001014.5(RPS10):c.3G>A (p.Met1Ile)	RPS10	Pathogenic	no assertion criteria provided
6186	NM_001014.5(RPS10):c.260dup (p.Glu88fs)	RPS10	Pathogenic	no assertion criteria provided
1794680	NM_001014.5(RPS10):c.268_275del (p.Val90fs)	RPS10-NUDT3	Pathogenic	criteria provided, multiple submitters, no conflicts
6187	NM_001014.5(RPS10):c.337C>T (p.Arg113Ter)	RPS10-NUDT3	Pathogenic	criteria provided, multiple submitters, no conflicts
3766746	NM_001014.5(RPS10):c.323-1G>A	RPS10	Likely pathogenic	criteria provided, single submitter
356422	NM_001014.5(RPS10):c.71A>G (p.Lys24Arg)	RPS10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356424	NM_001014.5(RPS10):c.1-3C>G	RPS10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
463371	NM_001014.5(RPS10):c.261G>A (p.Pro87=)	RPS10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904984	NM_001014.5(RPS10):c.437C>T (p.Ser146Leu)	RPS10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
356421	NM_001014.5(RPS10):c.111C>G (p.Asp37Glu)	RPS10-NUDT3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4278479	NM_001144758.3(PHLDB1):c.1805G>A (p.Arg602Gln)	PHLDB1	Uncertain significance	criteria provided, single submitter
1521087	NM_001014.5(RPS10):c.322+3A>G	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
2043241	NM_001014.5(RPS10):c.493C>G (p.Gln165Glu)	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
2188557	NM_001014.5(RPS10):c.473G>A (p.Arg158His)	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
225461	NM_001014.5(RPS10):c.322+2_322+4dup	RPS10	Uncertain significance	criteria provided, single submitter
2699015	NM_001014.5(RPS10):c.481G>T (p.Gly161Cys)	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
2869551	NM_001014.5(RPS10):c.22C>T (p.Arg8Trp)	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
3315280	NM_001014.5(RPS10):c.203A>G (p.Tyr68Cys)	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
3435298	NM_001014.5(RPS10):c.286C>T (p.Arg96Cys)	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
356418	NM_001014.5(RPS10):c.*25G>T	RPS10	Uncertain significance	criteria provided, single submitter
356420	NM_001014.5(RPS10):c.364G>A (p.Ala122Thr)	RPS10	Uncertain significance	criteria provided, single submitter
3593508	NM_001014.5(RPS10):c.488C>A (p.Pro163Gln)	RPS10	Uncertain significance	criteria provided, single submitter
3593510	NM_001014.5(RPS10):c.485A>G (p.Gln162Arg)	RPS10	Uncertain significance	criteria provided, single submitter
3593511	NM_001014.5(RPS10):c.331G>A (p.Gly111Ser)	RPS10	Uncertain significance	criteria provided, multiple submitters, no conflicts
3593513	NM_001014.5(RPS10):c.290G>C (p.Ser97Thr)	RPS10	Uncertain significance	criteria provided, single submitter
3593516	NM_001014.5(RPS10):c.256C>T (p.Pro86Ser)	RPS10	Uncertain significance	criteria provided, single submitter
3593517	NM_001014.5(RPS10):c.151-20A>C	RPS10	Uncertain significance	criteria provided, single submitter
3593518	NM_001014.5(RPS10):c.77A>T (p.Asp26Val)	RPS10	Uncertain significance	criteria provided, single submitter
3593519	NM_001014.5(RPS10):c.31A>G (p.Ile11Val)	RPS10	Uncertain significance	criteria provided, single submitter
3593520	NM_001014.5(RPS10):c.10C>G (p.Pro4Ala)	RPS10	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
RPS10	Definitive	Unknown	Diamond-Blackfan anemia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS10	Orphanet:124	Diamond-Blackfan anemia

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPS10	HGNC:10383	ENSG00000124614	P46783	Small ribosomal subunit protein eS10	gencc,clinvar
PHLDB1	HGNC:23697	ENSG00000019144	Q86UU1	Pleckstrin homology-like domain family B member 1	clinvar
RPS10-NUDT3	HGNC:49181	ENSG00000270800		RPS10-NUDT3 readthrough	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS10	Small ribosomal subunit protein eS10	Component of the 40S ribosomal subunit.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS10	Other/Unknown	no		Plectin_eS10_N, WH-like_DNA-bd_sf, Ribosomal_eS10
PHLDB1	Scaffold/PPI	no		FHA_dom, PH_domain, SMAD_FHA_dom_sf
RPS10-NUDT3	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left ovary	1
primordial germ cell in gonad	1
right ovary	1
middle frontal gyrus	1
sural nerve	1
tibial nerve	1
cortical plate	1
ganglionic eminence	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS10	134	ubiquitous	marker	primordial germ cell in gonad, left ovary, right ovary
PHLDB1	281	ubiquitous	marker	sural nerve, tibial nerve, middle frontal gyrus
RPS10-NUDT3	133	ubiquitous	marker	cortical plate, ganglionic eminence, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPS10	4,418
PHLDB1	722
RPS10-NUDT3	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS10	P46783	200

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PHLDB1	Q86UU1	60.40

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. Enrichment computed across 3 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	RPS10
Cap-dependent Translation Initiation	1	308.6×	0.016	RPS10
SARS-CoV-1 modulates host translation machinery	1	308.6×	0.016	RPS10
Eukaryotic Translation Elongation	1	278.5×	0.016	RPS10
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1	271.9×	0.016	RPS10
Nonsense-Mediated Decay (NMD)	1	233.1×	0.016	RPS10
SARS-CoV-2 modulates host translation machinery	1	223.9×	0.016	RPS10
Influenza Viral RNA Transcription and Replication	1	215.5×	0.016	RPS10
Formation of the ternary complex, and subsequently, the 43S complex	1	215.5×	0.016	RPS10
Selenoamino acid metabolism	1	196.9×	0.016	RPS10
Translation initiation complex formation	1	190.3×	0.016	RPS10
Ribosomal scanning and start codon recognition	1	190.3×	0.016	RPS10
Influenza Infection	1	175.7×	0.016	RPS10
SARS-CoV-1-host interactions	1	175.7×	0.016	RPS10
Cellular response to starvation	1	165.5×	0.016	RPS10
rRNA processing in the nucleus and cytosol	1	160.8×	0.016	RPS10
rRNA processing	1	146.4×	0.016	RPS10
SARS-CoV-1 Infection	1	142.8×	0.016	RPS10
Peptide chain elongation	1	126.9×	0.016	RPS10
Viral mRNA Translation	1	126.9×	0.016	RPS10
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	1	125.5×	0.016	RPS10
Signaling by ROBO receptors	1	124.1×	0.016	RPS10
Selenocysteine synthesis	1	120.2×	0.016	RPS10
Eukaryotic Translation Termination	1	120.2×	0.016	RPS10
SARS-CoV-2-host interactions	1	119.0×	0.016	RPS10
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	1	117.7×	0.016	RPS10
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	1	117.7×	0.016	RPS10
Formation of a pool of free 40S subunits	1	112.0×	0.016	RPS10
Response of EIF2AK4 (GCN2) to amino acid deficiency	1	110.9×	0.016	RPS10
L13a-mediated translational silencing of Ceruloplasmin expression	1	101.1×	0.016	RPS10

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
basement membrane organization	1	255.3×	0.012	PHLDB1
cytoplasmic translation	1	92.6×	0.016	RPS10
translation	1	51.4×	0.019	RPS10

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
RPS10	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS10	2	4
PHLDB1	0	0
RPS10-NUDT3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS10
MOLIBRESIB	2	RPS10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPS10	97	Binding:97
PHLDB1	1	Binding:1

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

2 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	RPS10
MOLIBRESIB	2	RPS10

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RPS10
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	2	PHLDB1, RPS10-NUDT3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PHLDB1	1	—
RPS10-NUDT3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.