Diamond-Blackfan anemia 21

disease

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Also known as DBA21diamond-blackfan anaemia 21

Summary

Diamond-Blackfan anemia 21 (MONDO:0031071) is a disease caused by HEATR3 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: HEATR3 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Diamond-Blackfan anemia 21
Mondo ID	MONDO:0031071
OMIM	620072
UMLS	C5774230
MedGen	1824003
GARD	0025692
Is cancer (heuristic)	no

Also known as: DBA21 · diamond-blackfan anaemia 21 · diamond-blackfan anemia 21

Data availability: 9 ClinVar variants · 2 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 21

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

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 4 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1300197	NM_182922.4(HEATR3):c.400T>C (p.Cys134Arg)	HEATR3	Pathogenic	no assertion criteria provided
1315571	NM_182922.4(HEATR3):c.1751G>A (p.Gly584Glu)	HEATR3	Pathogenic/Likely pathogenic	no assertion criteria provided
1321318	NM_182922.4(HEATR3):c.1337G>A (p.Cys446Tyr)	HEATR3	Pathogenic	no assertion criteria provided
1334102	NM_182922.4(HEATR3):c.399+1G>T	HEATR3	Pathogenic	criteria provided, single submitter
1334103	NM_182922.4(HEATR3):c.719C>T (p.Pro240Leu)	HEATR3	Pathogenic	criteria provided, single submitter
3366316	NM_182922.4(HEATR3):c.1253T>A (p.Val418Asp)	HEATR3	Uncertain significance	criteria provided, single submitter
3366317	NM_182922.4(HEATR3):c.1397C>T (p.Ala466Val)	HEATR3	Uncertain significance	criteria provided, single submitter
3377775	NM_182922.4(HEATR3):c.239C>T (p.Ala80Val)	HEATR3	Uncertain significance	criteria provided, single submitter
3602667	NM_182922.4(HEATR3):c.2024A>G (p.Glu675Gly)	HEATR3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
HEATR3	Strong	Autosomal recessive	Diamond-Blackfan anemia 21	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HEATR3	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
HEATR3	HGNC:26087	ENSG00000155393	Q7Z4Q2	HEAT repeat-containing protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HEATR3	HEAT repeat-containing protein 3	Plays a role in ribosome biogenesis and in nuclear import of the 60S ribosomal protein L5/large ribosomal subunit protein uL18 (RPL5).

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)
HEATR3	Other/Unknown	no		ARM-like, ARM-type_fold, SYO1-like

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HEATR3	248	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HEATR3	2,193

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HEATR3	Q7Z4Q2	83.07

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
erythrocyte maturation	1	842.6×	0.003	HEATR3
ribosomal large subunit biogenesis	1	443.5×	0.003	HEATR3
protein import into nucleus	1	144.0×	0.007	HEATR3

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
HEATR3	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	HEATR3

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)
HEATR3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: HEATR3