Diamond-Blackfan anemia 15 with mandibulofacial dysostosis

Summary

Diamond-Blackfan anemia 15 with mandibulofacial dysostosis (MONDO:0011639) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 15 with mandibulofacial dysostosis
Mondo ID	MONDO:0011639
OMIM	606164
DOID	DOID:0111894
UMLS	C4225411
MedGen	902755
GARD	0015390
Is cancer (heuristic)	no

Also known as: DBA15 · Diamond Blackfan anaemia 15 with mandibulofacial dysostosis · Diamond Blackfan anemia 15 with mandibulofacial dysostosis · Diamond-Blackfan anaemia caused by mutation in RPS28 · Diamond-Blackfan anemia 15 with mandibulofacial dysostosis · Diamond-Blackfan anemia caused by mutation in RPS28 · RPS28 Diamond-Blackfan anaemia · RPS28 Diamond-Blackfan anemia

Data availability: 5 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 15 with mandibulofacial dysostosis

Related subtypes (21): Diamond-Blackfan anemia 1, Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, Diamond-Blackfan anemia 2, 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 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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
187847	NM_058163.3(TSR2):c.191A>G (p.Glu64Gly)	TSR2	Pathogenic	criteria provided, single submitter
187848	NM_001031.5(RPS28):c.1A>G (p.Met1Val)	RPS28	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1244664	NM_001031.5(RPS28):c.*16+23T>C	RPS28	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 3 · 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
RPS28	Moderate	Autosomal dominant	Diamond-Blackfan anemia 15 with mandibulofacial dysostosis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPS28	Orphanet:124	Diamond-Blackfan anemia
RPS26	Orphanet:124	Diamond-Blackfan anemia
TSR2	Orphanet:124	Diamond-Blackfan anemia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPS28	HGNC:10418	ENSG00000233927	P62857	Small ribosomal subunit protein eS28	gencc,clinvar
RPS26	HGNC:10414	ENSG00000197728	P62854	Small ribosomal subunit protein eS26	clinvar
TSR2	HGNC:25455	ENSG00000158526	Q969E8	Pre-rRNA-processing protein TSR2 homolog	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPS28	Small ribosomal subunit protein eS28	Component of the small ribosomal subunit.
RPS26	Small ribosomal subunit protein eS26	Component of the small ribosomal subunit.
TSR2	Pre-rRNA-processing protein TSR2 homolog	May be involved in 20S pre-rRNA processing.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPS28	Other/Unknown	no		Ribosomal_eS28, NA-bd_OB-fold, Ribosomal_eS28_CS
RPS26	Other/Unknown	no		Ribosomal_eS26, Ribosomal_eS26_sf, Ribosomal_eS26_CS
TSR2	Other/Unknown	no		Pre-rRNA_process_TSR2

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
mucosa of transverse colon	2
adenohypophysis	1
lower esophagus mucosa	1
granulocyte	1
left adrenal gland cortex	1
globus pallidus	1
medial globus pallidus	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPS28	250	ubiquitous	marker	lower esophagus mucosa, adenohypophysis, mucosa of transverse colon
RPS26	140	ubiquitous	marker	granulocyte, left adrenal gland cortex, mucosa of transverse colon
TSR2	289	ubiquitous	marker	tendon of biceps brachii, medial globus pallidus, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSR2	1,969
RPS26	829
RPS28	637

Intra-cohort edges

A	B	Sources
RPS26	TSR2	biogrid_interaction, intact

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS28	P62857	214
RPS26	P62854	190

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSR2	Q969E8	74.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 50. Enrichment computed across 3 evidence-associated genes (2 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 2 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	2	308.6×	1e-04	RPS28, RPS26
Cap-dependent Translation Initiation	2	308.6×	1e-04	RPS28, RPS26
SARS-CoV-1 modulates host translation machinery	2	308.6×	1e-04	RPS28, RPS26
Eukaryotic Translation Elongation	2	278.5×	1e-04	RPS28, RPS26
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	2	271.9×	1e-04	RPS28, RPS26
Nonsense-Mediated Decay (NMD)	2	233.1×	1e-04	RPS28, RPS26
SARS-CoV-2 modulates host translation machinery	2	223.9×	1e-04	RPS28, RPS26
Influenza Viral RNA Transcription and Replication	2	215.5×	1e-04	RPS28, RPS26
Formation of the ternary complex, and subsequently, the 43S complex	2	215.5×	1e-04	RPS28, RPS26
Selenoamino acid metabolism	2	196.9×	1e-04	RPS28, RPS26
Translation initiation complex formation	2	190.3×	1e-04	RPS28, RPS26
Ribosomal scanning and start codon recognition	2	190.3×	1e-04	RPS28, RPS26
Influenza Infection	2	175.7×	1e-04	RPS28, RPS26
SARS-CoV-1-host interactions	2	175.7×	1e-04	RPS28, RPS26
Cellular response to starvation	2	165.5×	1e-04	RPS28, RPS26
rRNA processing in the nucleus and cytosol	2	160.8×	1e-04	RPS28, RPS26
rRNA processing	2	146.4×	1e-04	RPS28, RPS26
SARS-CoV-1 Infection	2	142.8×	1e-04	RPS28, RPS26
Peptide chain elongation	2	126.9×	1e-04	RPS28, RPS26
Viral mRNA Translation	2	126.9×	1e-04	RPS28, RPS26
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	2	125.5×	1e-04	RPS28, RPS26
Signaling by ROBO receptors	2	124.1×	1e-04	RPS28, RPS26
Selenocysteine synthesis	2	120.2×	1e-04	RPS28, RPS26
Eukaryotic Translation Termination	2	120.2×	1e-04	RPS28, RPS26
SARS-CoV-2-host interactions	2	119.0×	1e-04	RPS28, RPS26
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	2	117.7×	1e-04	RPS28, RPS26
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	2	117.7×	1e-04	RPS28, RPS26
Formation of a pool of free 40S subunits	2	112.0×	1e-04	RPS28, RPS26
Response of EIF2AK4 (GCN2) to amino acid deficiency	2	110.9×	1e-04	RPS28, RPS26
L13a-mediated translational silencing of Ceruloplasmin expression	2	101.1×	2e-04	RPS28, 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cytoplasmic translation	2	123.5×	8e-04	RPS28, RPS26
translation	2	68.5×	0.001	RPS28, RPS26
negative regulation of RNA splicing	1	802.5×	0.004	RPS26
ribosomal small subunit assembly	1	468.1×	0.005	RPS28
maturation of SSU-rRNA	1	255.3×	0.006	RPS28
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	224.7×	0.006	TSR2
ribosome biogenesis	1	208.1×	0.006	RPS28
ribosomal small subunit biogenesis	1	75.9×	0.015	RPS28
rRNA processing	1	47.2×	0.021	RPS28

Therapeutics

Drug target analysis

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

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
RPS28	GENTAMICIN SULFATE
RPS26	GENTAMICIN SULFATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RPS28	1	4
RPS26	1	4
TSR2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS26, RPS28

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RPS28	90	Binding:90
RPS26	89	Binding:89

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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, RPS28

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RPS28, 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	TSR2

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)
TSR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.