Dyskeratosis congenita, autosomal recessive 3

Summary

Dyskeratosis congenita, autosomal recessive 3 (MONDO:0013520) is a disease caused by WRAP53 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: WRAP53 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 86

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyskeratosis congenita, autosomal recessive 3
Mondo ID	MONDO:0013520
OMIM	613988
DOID	DOID:0070019
NCIT	C176927
UMLS	C3151442
MedGen	462792
GARD	0015740
Is cancer (heuristic)	no

Also known as: DKCB3 · dyskeratosis congenita, autosomal recessive 3 · dyskeratosis congenita, autosomal recessive type 3

Data availability: 86 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › dyskeratosis congenita, autosomal recessive 3

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

86 retrieved; paginated sample, class counts are floors:

47 uncertain significance, 19 conflicting classifications of pathogenicity, 11 benign/likely benign, 4 benign, 2 likely benign, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
30976	NM_001143992.2(WRAP53):c.1126C>T (p.His376Tyr)	WRAP53	Pathogenic	no assertion criteria provided
638511	NM_001143992.2(WRAP53):c.1118del (p.Leu373fs)	WRAP53	Pathogenic	criteria provided, single submitter
41252	NM_001143992.2(WRAP53):c.492C>A (p.Phe164Leu)	WRAP53	Likely pathogenic	criteria provided, single submitter
1675152	NM_001143992.2(WRAP53):c.956-6del	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1912927	NM_001143992.2(WRAP53):c.509del (p.Asn170fs)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1981385	NM_001143992.2(WRAP53):c.438G>A (p.Trp146Ter)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2902230	NM_001143992.2(WRAP53):c.823-11C>G	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30975	NM_001143992.2(WRAP53):c.1192C>T (p.Arg398Trp)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325654	NM_001143992.2(WRAP53):c.495C>T (p.Ser165=)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325656	NM_001143992.2(WRAP53):c.822+10G>A	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325658	NM_001143992.2(WRAP53):c.834G>A (p.Thr278=)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325661	NM_001143992.2(WRAP53):c.1035C>T (p.Tyr345=)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325662	NM_001143992.2(WRAP53):c.1269-13C>T	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3583081	NM_001143992.2(WRAP53):c.1257del (p.Phe419fs)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41251	NM_001143992.2(WRAP53):c.1303G>A (p.Gly435Arg)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
742999	NM_001143992.2(WRAP53):c.1521C>T (p.His507=)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
744284	NM_001143992.2(WRAP53):c.720A>G (p.Pro240=)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889405	NM_001143992.2(WRAP53):c.432-15C>G	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889406	NM_001143992.2(WRAP53):c.643-4A>G	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
890090	NM_001143992.2(WRAP53):c.956-14C>T	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
891848	NM_001143992.2(WRAP53):c.330C>T (p.Asn110=)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
891911	NM_001143992.2(WRAP53):c.1537C>G (p.Arg513Gly)	WRAP53	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
325647	NM_018081.2(WRAP53):c.-255G>A	LOC130060173	Uncertain significance	criteria provided, single submitter
325651	NM_001143992.2(WRAP53):c.187G>A (p.Val63Met)	TP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
1005376	NM_001143992.2(WRAP53):c.794G>A (p.Arg265Gln)	WRAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
1010874	NM_001143992.2(WRAP53):c.767T>C (p.Ile256Thr)	WRAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
1163410	NM_001143992.2(WRAP53):c.919C>T (p.Arg307Trp)	WRAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
1305946	NM_001143992.2(WRAP53):c.1049del (p.Gly350fs)	WRAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts
1327075	NM_001143992.2(WRAP53):c.1168G>A (p.Ala390Thr)	WRAP53	Uncertain significance	criteria provided, single submitter
1357494	NM_001143992.2(WRAP53):c.1517G>A (p.Arg506His)	WRAP53	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 21 · 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
WRAP53	Strong	Autosomal recessive	dyskeratosis congenita, autosomal recessive 3	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WRAP53	Orphanet:1775	Dyskeratosis congenita
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WRAP53	HGNC:25522	ENSG00000141499	Q9BUR4	Telomerase Cajal body protein 1	gencc,clinvar
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WRAP53	Telomerase Cajal body protein 1	RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies.
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: 2 · 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
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WRAP53	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchus	1
epithelium of bronchus	1
right uterine tube	1
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
WRAP53	237	ubiquitous	marker	right uterine tube, epithelium of bronchus, bronchus
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
WRAP53	1,303

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53	P04637	313
WRAP53	Q9BUR4	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 54. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Association of TriC/CCT with target proteins during biosynthesis	2	292.8×	6e-04	WRAP53, TP53
Loss of function of TP53 in cancer due to loss of tetramerization ability	1	5710.0×	0.005	TP53
Regulation of TP53 Expression	1	2855.0×	0.006	TP53
Transcriptional activation of cell cycle inhibitor p21	1	1427.5×	0.009	TP53
Activation of NOXA and translocation to mitochondria	1	951.7×	0.009	TP53
RUNX3 regulates CDKN1A transcription	1	815.7×	0.009	TP53
PI5P Regulates TP53 Acetylation	1	634.4×	0.009	TP53
Activation of PUMA and translocation to mitochondria	1	571.0×	0.009	TP53
TP53 Regulates Transcription of Caspase Activators and Caspases	1	475.8×	0.009	TP53
TP53 Regulates Transcription of Death Receptors and Ligands	1	475.8×	0.009	TP53
Urea cycle	1	439.2×	0.009	TP53
Regulation of TP53 Activity through Association with Co-factors	1	407.9×	0.009	TP53
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	380.7×	0.009	TP53
Stabilization of p53	1	380.7×	0.009	TP53
TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest	1	356.9×	0.009	TP53
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	1	335.9×	0.009	TP53
Zygotic genome activation (ZGA)	1	335.9×	0.009	TP53
Regulation of NF-kappa B signaling	1	317.2×	0.009	TP53
Extension of Telomeres	1	300.5×	0.009	WRAP53
TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest	1	300.5×	0.009	TP53
SUMOylation of transcription factors	1	285.5×	0.009	TP53
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	271.9×	0.009	TP53
Regulation of TP53 Activity through Methylation	1	271.9×	0.009	TP53
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	1	259.6×	0.009	TP53
Telomere Extension By Telomerase	1	228.4×	0.009	WRAP53
Regulation of TP53 Activity through Acetylation	1	228.4×	0.009	TP53
Pyroptosis	1	211.5×	0.009	TP53
Telomere Maintenance	1	184.2×	0.010	WRAP53
Oncogene Induced Senescence	1	167.9×	0.011	TP53
Chaperonin-mediated protein folding	1	150.3×	0.012	WRAP53

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
telomere formation via telomerase	1	8426.0×	0.003	WRAP53
RNA folding	1	8426.0×	0.003	WRAP53
negative regulation of helicase activity	1	8426.0×	0.003	TP53
cellular response to actinomycin D	1	8426.0×	0.003	TP53
regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1	8426.0×	0.003	TP53
negative regulation of G1 to G0 transition	1	8426.0×	0.003	TP53
positive regulation of mitochondrial membrane permeability	1	4213.0×	0.003	TP53
oligodendrocyte apoptotic process	1	4213.0×	0.003	TP53
negative regulation of glucose catabolic process to lactate via pyruvate	1	4213.0×	0.003	TP53
protein localization to Cajal body	1	4213.0×	0.003	WRAP53
negative regulation of pentose-phosphate shunt	1	4213.0×	0.003	TP53
obsolete homolactic fermentation	1	2808.7×	0.003	TP53
signal transduction by p53 class mediator	1	2808.7×	0.003	TP53
negative regulation of miRNA processing	1	2808.7×	0.003	TP53
positive regulation of establishment of protein localization to telomere	1	2808.7×	0.003	WRAP53
intrinsic apoptotic signaling pathway in response to hypoxia	1	2808.7×	0.003	TP53
regulation of fibroblast apoptotic process	1	2808.7×	0.003	TP53
T cell proliferation involved in immune response	1	2106.5×	0.003	TP53
Cajal body organization	1	2106.5×	0.003	WRAP53
positive regulation of programmed necrotic cell death	1	2106.5×	0.003	TP53
oxidative stress-induced premature senescence	1	2106.5×	0.003	TP53
B cell lineage commitment	1	1685.2×	0.003	TP53
T cell lineage commitment	1	1685.2×	0.003	TP53
mRNA transcription	1	1685.2×	0.003	TP53
positive regulation of RNA polymerase II transcription preinitiation complex assembly	1	1685.2×	0.003	TP53
positive regulation of thymocyte apoptotic process	1	1685.2×	0.003	TP53
cellular response to UV-C	1	1685.2×	0.003	TP53
scaRNA localization to Cajal body	1	1685.2×	0.003	WRAP53
regulation of mitochondrial membrane permeability involved in apoptotic process	1	1404.3×	0.003	TP53
viral process	1	1203.7×	0.003	TP53

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
WRAP53	0	0

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
WRAP53	2	Binding:2

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: 2; 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	1	WRAP53

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)
WRAP53	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.