Johanson-Blizzard syndrome

Summary

Johanson-Blizzard syndrome (MONDO:0009479) is a disease caused by UBR1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: Unknown (Europe) [Orphanet-validated]
• Causal gene: UBR1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 46
• Phenotypes (HPO): 37

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.4	Europe	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000430	Underdeveloped nasal alae	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001511	Intrauterine growth retardation	Very frequent (80-99%)
HP:0001596	Alopecia	Very frequent (80-99%)
HP:0001732	Abnormality of the pancreas	Very frequent (80-99%)
HP:0001738	Exocrine pancreatic insufficiency	Very frequent (80-99%)
HP:0002024	Malabsorption	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0010720	Abnormal hair pattern	Very frequent (80-99%)
HP:0000142	Abnormality of the vagina	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Frequent (30-79%)
HP:0000632	Lacrimation abnormality	Frequent (30-79%)
HP:0000677	Oligodontia	Frequent (30-79%)
HP:0000684	Delayed eruption of teeth	Frequent (30-79%)
HP:0000691	Microdontia	Frequent (30-79%)
HP:0001092	Absent lacrimal punctum	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001545	Anteriorly placed anus	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0002023	Anal atresia	Frequent (30-79%)
HP:0002750	Delayed skeletal maturation	Frequent (30-79%)
HP:0003075	Hypoproteinemia	Frequent (30-79%)
HP:0010460	Abnormality of the female genitalia	Frequent (30-79%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0000819	Diabetes mellitus	Occasional (5-29%)
HP:0000969	Edema	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001522	Death in infancy	Occasional (5-29%)
HP:0001651	Dextrocardia	Occasional (5-29%)
HP:0001671	Abnormal cardiac septum morphology	Occasional (5-29%)
HP:0005288	Abnormality of the nares	Occasional (5-29%)
HP:0008736	Hypoplasia of penis	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Johanson-Blizzard syndrome
Mondo ID	MONDO:0009479
MeSH	C535880, C564907
OMIM	243800, 260450
Orphanet	2315
DOID	DOID:14694
ICD-11	1427330812
SNOMED CT	75979009
UMLS	C0175692
MedGen	59798
GARD	0000080
NORD	1311
Is cancer (heuristic)	no

Also known as: JBS · Johanson-Blizzard syndrome · nasal alar hypoplasia, hypothyroidism, pancreatic achylia and congenital deafness · pancreatic insufficiency, combined exocrine

Data availability: 46 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Johanson-Blizzard syndrome

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

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

46 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 11 likely pathogenic, 9 pathogenic, 6 conflicting classifications of pathogenicity, 4 benign, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1251994	NM_174916.3(UBR1):c.4054-2A>G	UBR1	Pathogenic	no assertion criteria provided
1323737	NM_174916.3(UBR1):c.4524T>A (p.Tyr1508Ter)	UBR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1328530	NM_174916.3(UBR1):c.529-13G>A	UBR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1709455	NM_174916.3(UBR1):c.2379+1G>C	UBR1	Pathogenic	criteria provided, single submitter
208624	NM_174916.3(UBR1):c.4107T>A (p.Cys1369Ter)	UBR1	Pathogenic	criteria provided, single submitter
31918	NM_174916.3(UBR1):c.1440-1G>A	UBR1	Pathogenic	no assertion criteria provided
4679	NM_174916.3(UBR1):c.2254+2T>C	UBR1	Pathogenic	no assertion criteria provided
4680	NM_174916.3(UBR1):c.1537C>T (p.Gln513Ter)	UBR1	Pathogenic	no assertion criteria provided
4681	NM_174916.3(UBR1):c.2839+5G>A	UBR1	Pathogenic	no assertion criteria provided
985549	NM_174916.3(UBR1):c.3055C>T (p.Arg1019Ter)	UBR1	Pathogenic	criteria provided, multiple submitters, no conflicts
4688527	NM_174916.3(UBR1):c.81+1G>C	LOC130056936	Likely pathogenic	criteria provided, single submitter
1027875	NM_174916.3(UBR1):c.1539+2T>G	UBR1	Likely pathogenic	criteria provided, single submitter
2137658	NM_174916.3(UBR1):c.4291T>C (p.Ser1431Pro)	UBR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2502313	NM_174916.3(UBR1):c.4745del (p.Asn1582fs)	UBR1	Likely pathogenic	criteria provided, single submitter
3076002	NM_174916.3(UBR1):c.2840-1G>A	UBR1	Likely pathogenic	criteria provided, single submitter
3381892	NM_174916.3(UBR1):c.3513T>G (p.Tyr1171Ter)	UBR1	Likely pathogenic	criteria provided, single submitter
3577125	NM_174916.3(UBR1):c.1876_1882del (p.Gly626fs)	UBR1	Likely pathogenic	criteria provided, single submitter
3577126	NM_174916.3(UBR1):c.1830dup (p.Leu611fs)	UBR1	Likely pathogenic	criteria provided, single submitter
3577127	NM_174916.3(UBR1):c.1396C>T (p.Gln466Ter)	UBR1	Likely pathogenic	criteria provided, single submitter
4077728	NM_174916.3(UBR1):c.3550del (p.His1184fs)	UBR1	Likely pathogenic	criteria provided, single submitter
429675	NM_174916.3(UBR1):c.1912-6T>G	UBR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029284	NM_174916.3(UBR1):c.2261G>A (p.Arg754His)	UBR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1408468	NM_174916.3(UBR1):c.4895C>T (p.Ala1632Val)	UBR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1706419	NM_174916.3(UBR1):c.752G>T (p.Cys251Phe)	UBR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
235664	NM_174916.3(UBR1):c.3290C>T (p.Thr1097Met)	UBR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2492627	NM_174916.3(UBR1):c.3775A>G (p.Ile1259Val)	UBR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
429676	NM_174916.3(UBR1):c.2273G>A (p.Gly758Glu)	UBR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029286	NM_174916.3(UBR1):c.947G>A (p.Arg316His)	UBR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1328529	NM_174916.3(UBR1):c.3848+5G>A	UBR1	Uncertain significance	criteria provided, single submitter
1805156	NM_174916.3(UBR1):c.593T>C (p.Ile198Thr)	UBR1	Uncertain significance	criteria provided, single submitter

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
UBR1	Definitive	Autosomal recessive	Johanson-Blizzard syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UBR1	Orphanet:2315	Johanson-Blizzard 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
UBR1	HGNC:16808	ENSG00000159459	Q8IWV7	E3 ubiquitin-protein ligase UBR1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UBR1	E3 ubiquitin-protein ligase UBR1	E3 ubiquitin-protein ligase which is a component of the N-end rule pathway.

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)
UBR1	Transcription factor	no	3.4.17.20	Znf_UBR, ClpS_core, Ribosomal_bL12_C/ClpS-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
epithelial cell of pancreas	1
germinal epithelium of ovary	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UBR1	261	ubiquitous	marker	epithelial cell of pancreas, germinal epithelium of ovary, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UBR1	2,944

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UBR1	Q8IWV7	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.027	UBR1

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
ubiquitin-dependent protein catabolic process via the N-end rule pathway	1	3370.4×	0.001	UBR1
cellular response to L-leucine	1	1404.3×	0.002	UBR1
negative regulation of TOR signaling	1	561.7×	0.003	UBR1
proteasome-mediated ubiquitin-dependent protein catabolic process	1	52.2×	0.024	UBR1
protein ubiquitination	1	41.4×	0.024	UBR1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UBR1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
UBR1	32	Binding:32

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
UBR1	3.4.17.20	carboxypeptidase U

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	UBR1

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)
UBR1	32	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.