Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies

Summary

Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (MONDO:0044319) is a disease caused by OTUD6B (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: OTUD6B (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 34
• Phenotypes (HPO): 53

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		12	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

53 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001250	Seizure	Very frequent (80-99%)
HP:0010864	Intellectual disability, severe	Very frequent (80-99%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000219	Thin upper lip vermilion	Frequent (30-79%)
HP:0000248	Brachycephaly	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000276	Long face	Frequent (30-79%)
HP:0000278	Retrognathia	Frequent (30-79%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000400	Macrotia	Frequent (30-79%)
HP:0000426	Prominent nasal bridge	Frequent (30-79%)
HP:0000445	Wide nose	Frequent (30-79%)
HP:0000470	Short neck	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000527	Long eyelashes	Frequent (30-79%)
HP:0000637	Long palpebral fissure	Frequent (30-79%)
HP:0000960	Sacral dimple	Frequent (30-79%)
HP:0001182	Tapered finger	Frequent (30-79%)
HP:0001187	Hyperextensibility of the finger joints	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001290	Generalized hypotonia	Frequent (30-79%)
HP:0001344	Absent speech	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001762	Talipes equinovarus	Frequent (30-79%)
HP:0001845	Overlapping toe	Frequent (30-79%)
HP:0002119	Ventriculomegaly	Frequent (30-79%)
HP:0002540	Inability to walk	Frequent (30-79%)
HP:0002553	Highly arched eyebrow	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0003121	Limb joint contracture	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004325	Decreased body weight	Frequent (30-79%)
HP:0005469	Flat occiput	Frequent (30-79%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0011304	Broad thumb	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0000028	Cryptorchidism	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0001166	Arachnodactyly	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0002120	Cerebral cortical atrophy	Occasional (5-29%)
HP:0002510	Spastic tetraplegia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies
Mondo ID	MONDO:0044319
OMIM	617452
Orphanet	505237
UMLS	C4479520
MedGen	1375601
GARD	0017942
Is cancer (heuristic)	no

Also known as: IDDFSDA · intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies

Data availability: 34 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies

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, Johanson-Blizzard 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, 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

34 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 8 pathogenic, 5 conflicting classifications of pathogenicity, 5 likely pathogenic, 2 benign, 2 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029424	NM_016023.5(OTUD6B):c.631G>T (p.Glu211Ter)	OTUD6B	Pathogenic	criteria provided, multiple submitters, no conflicts
1333287	NM_016023.5(OTUD6B):c.192_195del (p.Glu65fs)	OTUD6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1334799	NM_016023.5(OTUD6B):c.527_528del (p.Val176fs)	OTUD6B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627380	NM_016023.5(OTUD6B):c.381_388del (p.Leu127fs)	OTUD6B	Pathogenic	criteria provided, single submitter
3341105	NM_016023.5(OTUD6B):c.83-1del	OTUD6B	Pathogenic	criteria provided, single submitter
375701	NM_016023.5(OTUD6B):c.343C>T (p.Arg115Ter)	OTUD6B	Pathogenic	criteria provided, multiple submitters, no conflicts
375702	NM_016023.5(OTUD6B):c.379_383del (p.Leu127fs)	OTUD6B	Pathogenic	criteria provided, single submitter
375703	NM_016023.5(OTUD6B):c.83-2A>G	OTUD6B	Pathogenic	criteria provided, single submitter
4687388	NM_016023.5(OTUD6B):c.287del (p.Pro96fs)	OTUD6B	Pathogenic	criteria provided, single submitter
967815	NM_016023.5(OTUD6B):c.189_190del (p.His63fs)	OTUD6B	Pathogenic	criteria provided, multiple submitters, no conflicts
1324839	NM_016023.5(OTUD6B):c.481A>T (p.Lys161Ter)	OTUD6B	Likely pathogenic	criteria provided, single submitter
1335813	NM_016023.5(OTUD6B):c.731T>G (p.Ile244Arg)	OTUD6B	Likely pathogenic	no assertion criteria provided
1810274	NM_016023.5(OTUD6B):c.401A>G (p.Glu134Gly)	OTUD6B	Likely pathogenic	criteria provided, single submitter
375704	NM_016023.5(OTUD6B):c.557A>G (p.Tyr186Cys)	OTUD6B	Likely pathogenic	criteria provided, single submitter
559925	NM_016023.5(OTUD6B):c.686T>C (p.Leu229Pro)	OTUD6B	Likely pathogenic	criteria provided, single submitter
1033385	NM_016023.5(OTUD6B):c.-15G>A	OTUD6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1388293	NM_016023.5(OTUD6B):c.839C>T (p.Ser280Leu)	OTUD6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
708377	NM_016023.5(OTUD6B):c.658G>A (p.Val220Ile)	OTUD6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
711501	NM_016023.5(OTUD6B):c.-39A>G	OTUD6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
711502	NM_016023.5(OTUD6B):c.389C>A (p.Ala130Asp)	OTUD6B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4056699	NM_016023.5(OTUD6B):c.54G>C (p.Arg18Ser)	LOC130000726	Uncertain significance	criteria provided, single submitter
1330413	NM_016023.5(OTUD6B):c.550G>A (p.Ala184Thr)	OTUD6B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339067	NM_016023.5(OTUD6B):c.677G>T (p.Gly226Val)	OTUD6B	Uncertain significance	criteria provided, single submitter
2434531	NM_016023.5(OTUD6B):c.316-1622G>A	OTUD6B	Uncertain significance	criteria provided, multiple submitters, no conflicts
3061832	NM_016023.5(OTUD6B):c.776C>A (p.Ser259Ter)	OTUD6B	Uncertain significance	criteria provided, single submitter
3061834	NM_016023.5(OTUD6B):c.692T>C (p.Leu231Pro)	OTUD6B	Uncertain significance	criteria provided, single submitter
3064925	NM_016023.5(OTUD6B):c.691C>G (p.Leu231Val)	OTUD6B	Uncertain significance	criteria provided, single submitter
3341106	NM_016023.5(OTUD6B):c.479A>G (p.Tyr160Cys)	OTUD6B	Uncertain significance	criteria provided, single submitter
3391306	NM_016023.5(OTUD6B):c.326C>G (p.Ala109Gly)	OTUD6B	Uncertain significance	criteria provided, single submitter
3595949	NM_016023.5(OTUD6B):c.189T>G (p.His63Gln)	OTUD6B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
OTUD6B	Strong	Autosomal recessive	intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OTUD6B	Orphanet:505237	Early-onset seizures-distal limb anomalies-facial dysmorphism-global developmental delay syndrome

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
OTUD6B	HGNC:24281	ENSG00000155100	Q8N6M0	Deubiquitinase OTUD6B	gencc,clinvar
OTUD4	HGNC:24949	ENSG00000164164	Q01804	OTU domain-containing protein 4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OTUD6B	Deubiquitinase OTUD6B	Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1.
OTUD4	OTU domain-containing protein 4	Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	2	36.6×	7e-04

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OTUD6B	Protease	yes		OTU_dom, Papain-like_cys_pep_sf, OTU_OTUD6
OTUD4	Protease	yes		OTU_dom, Papain-like_cys_pep_sf, Peptidase_C85-like

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
calcaneal tendon	1
epithelial cell of pancreas	1
sural nerve	1
Brodmann (1909) area 10	1
middle frontal gyrus	1
paraflocculus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OTUD6B	249	ubiquitous	marker	sural nerve, epithelial cell of pancreas, calcaneal tendon
OTUD4	295	ubiquitous	marker	middle frontal gyrus, Brodmann (1909) area 10, paraflocculus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OTUD4	2,337
OTUD6B	1,379

Intra-cohort edges

A	B	Sources
OTUD4	OTUD6B	string_interaction

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OTUD6B	Q8N6M0	85.27
OTUD4	Q01804	49.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of protein K48-linked deubiquitination	1	8426.0×	0.002	OTUD4
negative regulation of interleukin-1-mediated signaling pathway	1	842.6×	0.003	OTUD4
DNA alkylation repair	1	766.0×	0.003	OTUD4
protein K11-linked deubiquitination	1	766.0×	0.003	OTUD4
proteasome assembly	1	766.0×	0.003	OTUD6B
proteolysis	2	34.2×	0.003	OTUD6B, OTUD4
negative regulation of toll-like receptor signaling pathway	1	421.3×	0.005	OTUD4
protein K48-linked deubiquitination	1	324.1×	0.005	OTUD4
protein K63-linked deubiquitination	1	312.1×	0.005	OTUD4
positive regulation of translation	1	113.9×	0.011	OTUD6B
antiviral innate immune response	1	113.9×	0.011	OTUD4
negative regulation of translation	1	98.0×	0.012	OTUD6B
protein deubiquitination	1	88.7×	0.012	OTUD6B
cell population proliferation	1	51.4×	0.019	OTUD6B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OTUD6B	0	0
OTUD4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
OTUD6B	2	Binding:2

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

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	2	OTUD6B, OTUD4
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
OTUD6B	2	—
OTUD4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.