Bone marrow failure syndrome 6

Summary

Bone marrow failure syndrome 6 (MONDO:0030015) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bone marrow failure syndrome 6
Mondo ID	MONDO:0030015
OMIM	618849
UMLS	C5394274
MedGen	1717739
GARD	0025508
Is cancer (heuristic)	no

Also known as: BMFS6 · BONE MARROW FAILURE SYNDROME 6 · bone marrow failure syndrome 6

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

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 6

Related subtypes (7): autosomal dominant aplasia and myelodysplasia, pancytopenia-developmental delay syndrome, bone marrow failure syndrome 3, bone marrow failure syndrome 4, 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

5 retrieved; paginated sample, class counts are floors:

5 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333555	NM_002393.5(MDM4):c.1147T>C (p.Ser383Pro)	MDM4	Uncertain significance	criteria provided, single submitter
1679681	NM_002393.5(MDM4):c.1045A>G (p.Ile349Val)	MDM4	Uncertain significance	criteria provided, single submitter
2394777	NM_002393.5(MDM4):c.536C>G (p.Ala179Gly)	MDM4	Uncertain significance	criteria provided, multiple submitters, no conflicts
3602675	NM_002393.5(MDM4):c.90dup (p.Leu31fs)	MDM4	Uncertain significance	criteria provided, single submitter
869418	NM_002393.5(MDM4):c.1361C>T (p.Thr454Met)	MDM4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
MDM4	Moderate	Autosomal dominant	bone marrow failure syndrome	2

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
MDM4	HGNC:6974	ENSG00000198625	O15151	Protein Mdm4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MDM4	Protein Mdm4	Contributes to p53/TP53 regulation.

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)
MDM4	Transcription factor	no		Znf_RING, Znf_RanBP2, SWIB_MDM2_domain

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
colonic epithelium	1
nipple	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MDM4	270	ubiquitous	marker	nipple, oocyte, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MDM4	3,431

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MDM4	O15151	39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 1 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
Stabilization of p53	1	761.3×	0.008	MDM4
p53-Dependent G1 DNA Damage Response	1	713.8×	0.008	MDM4
p53-Dependent G1/S DNA damage checkpoint	1	713.8×	0.008	MDM4
G1/S DNA Damage Checkpoints	1	671.8×	0.008	MDM4
Regulation of TP53 Activity through Methylation	1	543.8×	0.008	MDM4
Regulation of TP53 Expression and Degradation	1	519.1×	0.008	MDM4
Oncogene Induced Senescence	1	335.9×	0.010	MDM4
Regulation of TP53 Degradation	1	292.8×	0.010	MDM4
Cellular Senescence	1	137.6×	0.017	MDM4
Regulation of TP53 Activity	1	132.8×	0.017	MDM4
Deubiquitination	1	124.1×	0.017	MDM4
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.017	MDM4
Oxidative Stress Induced Senescence	1	90.6×	0.019	MDM4
Cell Cycle Checkpoints	1	88.5×	0.019	MDM4
Transcriptional Regulation by TP53	1	62.1×	0.026	MDM4
Ub-specific processing proteases	1	53.1×	0.028	MDM4
Cellular responses to stress	1	36.8×	0.037	MDM4
Cell Cycle	1	36.0×	0.037	MDM4
Cellular responses to stimuli	1	31.5×	0.040	MDM4
RNA Polymerase II Transcription	1	22.5×	0.053	MDM4
Post-translational protein modification	1	19.2×	0.060	MDM4
Gene expression (Transcription)	1	17.8×	0.061	MDM4
Generic Transcription Pathway	1	15.1×	0.069	MDM4
Metabolism of proteins	1	12.4×	0.081	MDM4

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
atrial septum development	1	2106.5×	0.004	MDM4
heart valve development	1	1532.0×	0.004	MDM4
atrioventricular valve morphogenesis	1	1203.7×	0.004	MDM4
negative regulation of signal transduction by p53 class mediator	1	1203.7×	0.004	MDM4
endocardial cushion morphogenesis	1	842.6×	0.004	MDM4
ventricular septum development	1	495.6×	0.006	MDM4
negative regulation of protein catabolic process	1	366.4×	0.006	MDM4
DNA damage response, signal transduction by p53 class mediator	1	358.6×	0.006	MDM4
cellular response to hypoxia	1	121.2×	0.015	MDM4
protein-containing complex assembly	1	113.9×	0.015	MDM4
regulation of cell cycle	1	74.6×	0.021	MDM4
protein stabilization	1	66.9×	0.021	MDM4
negative regulation of cell population proliferation	1	42.1×	0.029	MDM4
protein ubiquitination	1	41.4×	0.029	MDM4
negative regulation of apoptotic process	1	34.8×	0.033	MDM4
negative regulation of DNA-templated transcription	1	31.6×	0.034	MDM4
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	MDM4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
MDM4	DIOSMIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MDM4	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIOSMIN	4	MDM4
VERTEPORFIN	4	MDM4
SIREMADLIN	2	MDM4
ALLICIN	2	MDM4
SAR-405838	1	MDM4
CGM-097	1	MDM4
ABT 737	1	MDM4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MDM4	149	Binding:148, Functional:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
MDM4	149

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

7 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)
DIOSMIN	4	MDM4
VERTEPORFIN	4	MDM4
SIREMADLIN	2	MDM4
ALLICIN	2	MDM4
SAR-405838	1	MDM4
CGM-097	1	MDM4
ABT 737	1	MDM4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MDM4
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.