Bone marrow failure syndrome 3

Summary

Bone marrow failure syndrome 3 (MONDO:0014887) is a disease caused by DNAJC21 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: DNAJC21 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 43

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bone marrow failure syndrome 3
Mondo ID	MONDO:0014887
OMIM	617052
UMLS	C4310744
MedGen	934711
GARD	0025030
Is cancer (heuristic)	no

Also known as: BMFS3 · bone marrow failure syndrome 3 · bone marrow failure syndrome caused by mutation in DNAJC21 · bone marrow failure syndrome type 3 · DNAJC21 bone marrow failure syndrome · DNAJC21-related bone marrow failure syndrome

Data availability: 43 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › bone marrow disorder › bone marrow failure syndrome › bone marrow failure syndrome 3

Related subtypes (7): autosomal dominant aplasia and myelodysplasia, pancytopenia-developmental delay syndrome, bone marrow failure syndrome 4, bone marrow failure syndrome 6, AMED syndrome, digenic, bone marrow failure syndrome 5, Ziegler-Huang syndrome

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

43 retrieved; paginated sample, class counts are floors:

12 pathogenic, 11 uncertain significance, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 benign, 3 likely pathogenic, 3 pathogenic/likely pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028445	NM_001012339.3(DNAJC21):c.1224dup (p.Gly409fs)	DNAJC21	Pathogenic	criteria provided, multiple submitters, no conflicts
1339571	NM_001012339.3(DNAJC21):c.148C>T (p.Gln50Ter)	DNAJC21	Pathogenic	criteria provided, single submitter
1339573	NM_001012339.3(DNAJC21):c.643_644delinsTTT (p.Lys215fs)	DNAJC21	Pathogenic	no assertion criteria provided
1394237	NM_001012339.3(DNAJC21):c.673G>T (p.Glu225Ter)	DNAJC21	Pathogenic	criteria provided, multiple submitters, no conflicts
222063	NM_001012339.3(DNAJC21):c.94C>G (p.Pro32Ala)	DNAJC21	Pathogenic	no assertion criteria provided
222064	NM_001012339.3(DNAJC21):c.517C>T (p.Arg173Ter)	DNAJC21	Pathogenic	criteria provided, multiple submitters, no conflicts
222065	NM_001012339.3(DNAJC21):c.793G>T (p.Glu265Ter)	DNAJC21	Pathogenic	no assertion criteria provided
222066	NM_001012339.3(DNAJC21):c.983+1G>A	DNAJC21	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065635	NM_001012339.3(DNAJC21):c.381delinsCTAGTGT (p.Leu127delinsPheTer)	DNAJC21	Pathogenic	criteria provided, single submitter
4280725	NM_001012339.3(DNAJC21):c.411del (p.Phe137fs)	DNAJC21	Pathogenic	criteria provided, single submitter
598950	NM_001012339.3(DNAJC21):c.544C>T (p.Arg182Ter)	DNAJC21	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
617606	NM_001012339.3(DNAJC21):c.520C>T (p.Gln174Ter)	DNAJC21	Pathogenic	no assertion criteria provided
617607	NM_001012339.3(DNAJC21):c.100A>G (p.Lys34Glu)	DNAJC21	Pathogenic	criteria provided, single submitter
802111	NM_001012339.3(DNAJC21):c.982del (p.Ala328fs)	DNAJC21	Pathogenic	criteria provided, single submitter
807409	NM_001012339.3(DNAJC21):c.647_666del (p.Arg216fs)	DNAJC21	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705479	NM_001012339.3(DNAJC21):c.1004C>A (p.Ser335Ter)	DNAJC21	Likely pathogenic	criteria provided, single submitter
253171	NM_001012339.3(DNAJC21):c.983+1G>T	DNAJC21	Likely pathogenic	criteria provided, single submitter
2585147	NM_001012339.3(DNAJC21):c.316-2A>C	DNAJC21	Likely pathogenic	criteria provided, single submitter
1031725	NM_001012339.3(DNAJC21):c.958G>A (p.Asp320Asn)	DNAJC21	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1164684	NM_001012339.3(DNAJC21):c.191+10A>G	DNAJC21	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1174703	NM_001012339.3(DNAJC21):c.1016G>A (p.Arg339Gln)	DNAJC21	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2635017	NM_001012339.3(DNAJC21):c.434A>G (p.Asp145Gly)	DNAJC21	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
790400	NM_001012339.3(DNAJC21):c.1024G>A (p.Val342Met)	DNAJC21	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009379	NM_001012339.3(DNAJC21):c.1481G>A (p.Arg494Gln)	DNAJC21	Uncertain significance	criteria provided, multiple submitters, no conflicts
1021219	NM_001012339.3(DNAJC21):c.335G>A (p.Arg112His)	DNAJC21	Uncertain significance	criteria provided, multiple submitters, no conflicts
1031724	NM_001012339.3(DNAJC21):c.1015C>T (p.Arg339Trp)	DNAJC21	Uncertain significance	criteria provided, single submitter
1303476	NM_001012339.3(DNAJC21):c.1368del (p.Lys456fs)	DNAJC21	Uncertain significance	criteria provided, multiple submitters, no conflicts
1336969	NM_001012339.3(DNAJC21):c.1186-531G>A	DNAJC21	Uncertain significance	criteria provided, multiple submitters, no conflicts
1372084	NM_001012339.3(DNAJC21):c.253A>G (p.Ser85Gly)	DNAJC21	Uncertain significance	criteria provided, multiple submitters, no conflicts
1427599	NM_001012339.3(DNAJC21):c.410T>C (p.Phe137Ser)	DNAJC21	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
DNAJC21	Definitive	Autosomal recessive	bone marrow failure syndrome 3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAJC21	Orphanet:811	Shwachman-Diamond syndrome

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
DNAJC21	HGNC:27030	ENSG00000168724	Q5F1R6	DnaJ homolog subfamily C member 21	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAJC21	DnaJ homolog subfamily C member 21	May act as a co-chaperone for HSP70.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAJC21	Transcription factor	no		DnaJ_domain, Matrin/U1-like-C_Znf_C2H2, Znf_C2H2_type

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
epithelial cell of pancreas	1
left testis	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAJC21	255	ubiquitous	marker	epithelial cell of pancreas, tibialis anterior, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNAJC21	1,048

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAJC21	Q5F1R6	72.10

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
protein folding	1	103.4×	0.010	DNAJC21

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
DNAJC21	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	DNAJC21

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)
DNAJC21	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.