Bone marrow failure syndrome 5

Summary

Bone marrow failure syndrome 5 (MONDO:0032573) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 51

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bone marrow failure syndrome 5
Mondo ID	MONDO:0032573
OMIM	618165
UMLS	C4748488
MedGen	1648380
GARD	0025706
Is cancer (heuristic)	no

Also known as: BMFS5

Data availability: 51 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 5

Related subtypes (7): autosomal dominant aplasia and myelodysplasia, pancytopenia-developmental delay syndrome, bone marrow failure syndrome 3, bone marrow failure syndrome 4, bone marrow failure syndrome 6, AMED syndrome, digenic, 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

51 retrieved; paginated sample, class counts are floors:

12 conflicting classifications of pathogenicity, 12 pathogenic, 10 pathogenic/likely pathogenic, 9 uncertain significance, 3 benign, 2 likely benign, 2 benign/likely benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance

ClinVar	Variant (HGVS)	Gene	Classification	Review
12356	NM_000546.6(TP53):c.743G>A (p.Arg248Gln)	TP53	Pathogenic	reviewed by expert panel
12359	NM_000546.6(TP53):c.722C>T (p.Ser241Phe)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12365	NM_000546.6(TP53):c.733G>A (p.Gly245Ser)	TP53	Pathogenic	reviewed by expert panel
12366	NM_000546.6(TP53):c.818G>A (p.Arg273His)	TP53	Pathogenic	reviewed by expert panel
12374	NM_000546.6(TP53):c.524G>A (p.Arg175His)	TP53	Pathogenic	reviewed by expert panel
12379	NM_000546.6(TP53):c.1010G>A (p.Arg337His)	TP53	Pathogenic/Likely pathogenic/Pathogenic, low penetrance	criteria provided, multiple submitters, no conflicts
127819	NM_000546.6(TP53):c.659A>G (p.Tyr220Cys)	TP53	Pathogenic	reviewed by expert panel
1341341	NM_000546.6(TP53):c.72dup (p.Leu25fs)	TP53	Pathogenic	criteria provided, single submitter
141963	NM_000546.6(TP53):c.473G>A (p.Arg158His)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142657	NM_000546.6(TP53):c.427G>A (p.Val143Met)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182968	NM_000546.6(TP53):c.842A>T (p.Asp281Val)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
182970	NM_000546.6(TP53):c.1024C>T (p.Arg342Ter)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
231146	NM_000546.6(TP53):c.1101-1G>A	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
376615	NM_000546.6(TP53):c.641A>G (p.His214Arg)	TP53	Pathogenic	reviewed by expert panel
376625	NM_000546.6(TP53):c.395A>G (p.Lys132Arg)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
376655	NM_000546.6(TP53):c.818G>T (p.Arg273Leu)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
376659	NM_000546.6(TP53):c.845G>C (p.Arg282Pro)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3892955	NC_000017.10:g.7578466_7590809del	TP53	Pathogenic	criteria provided, single submitter
428873	NM_000546.6(TP53):c.389T>C (p.Leu130Pro)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
549855	NM_000546.6(TP53):c.1077del (p.Ser362fs)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
549856	NM_000546.6(TP53):c.1083del (p.Ser362fs)	TP53	Pathogenic	criteria provided, multiple submitters, no conflicts
634674	NM_000546.6(TP53):c.298del (p.Gln100fs)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
634682	NM_000546.6(TP53):c.817C>G (p.Arg273Gly)	TP53	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100814	NM_000546.6(TP53):c.587G>T (p.Arg196Leu)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1021706	NM_000546.6(TP53):c.875A>C (p.Lys292Thr)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127810	NM_000546.6(TP53):c.466C>T (p.Arg156Cys)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127818	NM_000546.6(TP53):c.604C>T (p.Arg202Cys)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141967	NM_000546.6(TP53):c.256G>A (p.Ala86Thr)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1481828	NM_000546.6(TP53):c.1080G>T (p.Gly360=)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
183071	NM_000546.6(TP53):c.649G>A (p.Val217Met)	TP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 20 · 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
TP53	Moderate	Autosomal dominant	bone marrow failure syndrome 5	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome
TP53	Orphanet:52688	Myelodysplastic syndrome
TP53	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
TP53	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
TP53	Orphanet:668	Osteosarcoma
TP53	Orphanet:67038	B-cell chronic lymphocytic leukemia
TP53	Orphanet:70573	Small cell lung cancer
TP53	Orphanet:96253	Cushing disease
TP53	Orphanet:99756	Alveolar rhabdomyosarcoma
TP53	Orphanet:99757	Embryonal rhabdomyosarcoma

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
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.

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)
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn

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
ganglionic eminence	1
tendon of biceps brachii	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 46. 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
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	11420.0×	0.004	TP53
Regulation of TP53 Expression	1	5710.0×	0.004	TP53
Transcriptional activation of cell cycle inhibitor p21	1	2855.0×	0.004	TP53
Activation of NOXA and translocation to mitochondria	1	1903.3×	0.004	TP53
RUNX3 regulates CDKN1A transcription	1	1631.4×	0.004	TP53
PI5P Regulates TP53 Acetylation	1	1268.9×	0.004	TP53
Activation of PUMA and translocation to mitochondria	1	1142.0×	0.004	TP53
TP53 Regulates Transcription of Caspase Activators and Caspases	1	951.7×	0.004	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	951.7×	0.004	TP53
Urea cycle	1	878.5×	0.004	TP53
Regulation of TP53 Activity through Association with Co-factors	1	815.7×	0.004	TP53
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	761.3×	0.004	TP53
Stabilization of p53	1	761.3×	0.004	TP53
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	713.8×	0.004	TP53
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	671.8×	0.004	TP53
Zygotic genome activation (ZGA)	1	671.8×	0.004	TP53
Regulation of NF-kappa B signaling	1	634.4×	0.004	TP53
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	601.0×	0.004	TP53
SUMOylation of transcription factors	1	571.0×	0.004	TP53
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	543.8×	0.004	TP53
Regulation of TP53 Activity through Methylation	1	543.8×	0.004	TP53
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1	519.1×	0.004	TP53
Regulation of TP53 Activity through Acetylation	1	456.8×	0.004	TP53
Pyroptosis	1	423.0×	0.005	TP53
Oncogene Induced Senescence	1	335.9×	0.005	TP53
Association of TriC/CCT with target proteins during biosynthesis	1	292.8×	0.006	TP53
Regulation of TP53 Degradation	1	292.8×	0.006	TP53
Ovarian tumor domain proteases	1	278.5×	0.006	TP53
Autodegradation of the E3 ubiquitin ligase COP1	1	265.6×	0.006	TP53
Transcriptional Regulation by VENTX	1	265.6×	0.006	TP53

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
negative regulation of helicase activity	1	16852.0×	0.002	TP53
cellular response to actinomycin D	1	16852.0×	0.002	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	16852.0×	0.002	TP53
negative regulation of G1 to G0 transition	1	16852.0×	0.002	TP53
positive regulation of mitochondrial membrane permeability	1	8426.0×	0.002	TP53
oligodendrocyte apoptotic process	1	8426.0×	0.002	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	8426.0×	0.002	TP53
negative regulation of pentose-phosphate shunt	1	8426.0×	0.002	TP53
obsolete homolactic fermentation	1	5617.3×	0.002	TP53
signal transduction by p53 class mediator	1	5617.3×	0.002	TP53
negative regulation of miRNA processing	1	5617.3×	0.002	TP53
intrinsic apoptotic signaling pathway in response to hypoxia	1	5617.3×	0.002	TP53
regulation of fibroblast apoptotic process	1	5617.3×	0.002	TP53
T cell proliferation involved in immune response	1	4213.0×	0.002	TP53
positive regulation of programmed necrotic cell death	1	4213.0×	0.002	TP53
oxidative stress-induced premature senescence	1	4213.0×	0.002	TP53
B cell lineage commitment	1	3370.4×	0.002	TP53
T cell lineage commitment	1	3370.4×	0.002	TP53
mRNA transcription	1	3370.4×	0.002	TP53
positive regulation of RNA polymerase II transcription preinitiation complex assembly	1	3370.4×	0.002	TP53
positive regulation of thymocyte apoptotic process	1	3370.4×	0.002	TP53
cellular response to UV-C	1	3370.4×	0.002	TP53
regulation of mitochondrial membrane permeability involved in apoptotic process	1	2808.7×	0.002	TP53
viral process	1	2407.4×	0.002	TP53
mitochondrial DNA repair	1	2407.4×	0.002	TP53
regulation of cell cycle G2/M phase transition	1	2407.4×	0.002	TP53
regulation of tissue remodeling	1	2106.5×	0.002	TP53
regulation of DNA damage response, signal transduction by p53 class mediator	1	2106.5×	0.002	TP53
response to salt stress	1	1872.4×	0.002	TP53
circadian behavior	1	1872.4×	0.002	TP53

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
TP53	NITROFURANTOIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TP53	869

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

30 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)
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53
VERTEPORFIN	4	TP53
CANDESARTAN CILEXETIL	4	TP53
DIENESTROL	4	TP53
CLOTRIMAZOLE	4	TP53
COLCHICINE	4	TP53
NABUMETONE	4	TP53
SALMETEROL XINAFOATE	4	TP53
AMIODARONE HYDROCHLORIDE	4	TP53
FURAZOLIDONE	4	TP53
AMOXAPINE	4	TP53
RALOXIFENE HYDROCHLORIDE	4	TP53
NICARDIPINE HYDROCHLORIDE	4	TP53
SULCONAZOLE NITRATE	4	TP53
PYRITHIONE ZINC	4	TP53
LACTIC ACID	4	TP53
OXYMETHOLONE	4	TP53
CHLOROXINE	4	TP53
PROPIOLACTONE	4	TP53
CLOMIPRAMINE HYDROCHLORIDE	4	TP53
PHENYL AMINOSALICYLATE	4	TP53
THIORIDAZINE HYDROCHLORIDE	4	TP53
AMITRIPTYLINE HYDROCHLORIDE	4	TP53
ETHOPROPAZINE HYDROCHLORIDE	4	TP53
MECHLORETHAMINE HYDROCHLORIDE	4	TP53
ECONAZOLE NITRATE	4	TP53
TRIFLUPROMAZINE HYDROCHLORIDE	4	TP53
PROCHLORPERAZINE EDISYLATE	4	TP53
DEQUALINIUM CHLORIDE	4	TP53

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TP53
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.