Diamond-Blackfan anemia 14 with mandibulofacial dysostosis

disease

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Also known as DBA14Diamond-Blackfan anaemia 14 with mandibulofacial dysostosis, X-linked recessiveDiamond-Blackfan anaemia caused by mutation in TSR2Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, X-linked recessiveDiamond-Blackfan anemia caused by mutation in TSR2TSR2 Diamond-Blackfan anaemiaTSR2 Diamond-Blackfan anemia

Summary

Diamond-Blackfan anemia 14 with mandibulofacial dysostosis (MONDO:0010493) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 14 with mandibulofacial dysostosis
Mondo ID	MONDO:0010493
OMIM	300946
DOID	DOID:0111897
UMLS	C4225422
MedGen	895657
GARD	0015275
Is cancer (heuristic)	no

Also known as: DBA14 · Diamond-Blackfan anaemia 14 with mandibulofacial dysostosis, X-linked recessive · Diamond-Blackfan anaemia caused by mutation in TSR2 · Diamond-Blackfan anemia 14 with mandibulofacial dysostosis · Diamond-Blackfan anemia 14 with mandibulofacial dysostosis, X-linked recessive · Diamond-Blackfan anemia caused by mutation in TSR2 · TSR2 Diamond-Blackfan anaemia · TSR2 Diamond-Blackfan anemia

Data availability: 2 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 14 with mandibulofacial dysostosis

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
187847	NM_058163.3(TSR2):c.191A>G (p.Glu64Gly)	TSR2	Pathogenic	criteria provided, single submitter
709009	NM_058163.3(TSR2):c.234T>C (p.Asp78=)	TSR2	Benign/Likely benign	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
TSR2	Supportive	Autosomal dominant	Diamond-Blackfan anemia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSR2	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
TSR2	HGNC:25455	ENSG00000158526	Q969E8	Pre-rRNA-processing protein TSR2 homolog	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSR2	Pre-rRNA-processing protein TSR2 homolog	May be involved in 20S pre-rRNA processing.

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)
TSR2	Other/Unknown	no		Pre-rRNA_process_TSR2

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
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
TSR2	289	ubiquitous	marker	tendon of biceps brachii, medial globus pallidus, globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSR2	1,969

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSR2	Q969E8	74.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	674.1×	0.001	TSR2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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.

Cohort genes: TSR2