Oculodentodigital dysplasia, autosomal recessive

Summary

Oculodentodigital dysplasia, autosomal recessive (MONDO:0009768) is a disease caused by GJA1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: GJA1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 247

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oculodentodigital dysplasia, autosomal recessive
Mondo ID	MONDO:0009768
MeSH	C567605
OMIM	257850
UMLS	C2749477
MedGen	412708
GARD	0015213
Is cancer (heuristic)	no

Also known as: autosomal recessive oculodentodigital dysplasia · oculodentodigital dysplasia, autosomal recessive · oculodentoosseous dysplasia recessive · ODOD recessive

Data availability: 247 ClinVar variants · 2 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 › oculodentodigital dysplasia, autosomal recessive

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, 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, dyskeratosis congenita, autosomal recessive 3, 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

247 retrieved; paginated sample, class counts are floors:

131 uncertain significance, 68 likely benign, 13 pathogenic, 12 conflicting classifications of pathogenicity, 9 pathogenic/likely pathogenic, 8 likely pathogenic, 5 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
501115	NM_080680.3(COL11A2):c.3877C>T (p.Arg1293Ter)	COL11A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028586	NM_000165.5(GJA1):c.142G>A (p.Glu48Lys)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16984	NM_000165.5(GJA1):c.61G>A (p.Gly21Arg)	GJA1	Pathogenic	criteria provided, single submitter
16985	NM_000165.5(GJA1):c.65G>A (p.Gly22Glu)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16988	NM_000165.5(GJA1):c.286G>A (p.Val96Met)	GJA1	Pathogenic	criteria provided, single submitter
16995	NM_000165.5(GJA1):c.97C>T (p.Arg33Ter)	GJA1	Pathogenic	no assertion criteria provided
16996	NM_000165.5(GJA1):c.227G>A (p.Arg76His)	GJA1	Pathogenic	no assertion criteria provided
16997	NM_000165.5(GJA1):c.226C>A (p.Arg76Ser)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1715214	NM_000165.5(GJA1):c.187A>G (p.Asn63Asp)	GJA1	Pathogenic	criteria provided, single submitter
203469	NM_000165.5(GJA1):c.131C>T (p.Ala44Val)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2169516	NM_000165.5(GJA1):c.113G>A (p.Gly38Glu)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2705428	NM_000165.5(GJA1):c.32T>A (p.Leu11His)	GJA1	Pathogenic	criteria provided, single submitter
3647870	NM_000165.5(GJA1):c.679G>C (p.Glu227Gln)	GJA1	Pathogenic	criteria provided, single submitter
435323	NM_000165.5(GJA1):c.119C>T (p.Ala40Val)	GJA1	Pathogenic	criteria provided, multiple submitters, no conflicts
435324	NM_000165.5(GJA1):c.443G>A (p.Arg148Gln)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
470213	NM_000165.5(GJA1):c.140A>T (p.Asp47Val)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
470215	NM_000165.5(GJA1):c.389T>C (p.Ile130Thr)	GJA1	Pathogenic	criteria provided, single submitter
470216	NM_000165.5(GJA1):c.413G>A (p.Gly138Asp)	GJA1	Pathogenic	criteria provided, multiple submitters, no conflicts
537755	NM_000165.5(GJA1):c.306G>C (p.Lys102Asn)	GJA1	Pathogenic	criteria provided, single submitter
537756	NM_000165.5(GJA1):c.412G>A (p.Gly138Ser)	GJA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
844190	NM_000165.5(GJA1):c.64G>A (p.Gly22Arg)	GJA1	Pathogenic	criteria provided, single submitter
941060	NM_000165.5(GJA1):c.53C>A (p.Ser18Ter)	GJA1	Pathogenic	criteria provided, single submitter
1345508	NM_000165.5(GJA1):c.196T>C (p.Tyr66His)	GJA1	Likely pathogenic	criteria provided, single submitter
1492359	NM_000165.5(GJA1):c.246C>G (p.Ile82Met)	GJA1	Likely pathogenic	criteria provided, single submitter
2136457	NM_000165.5(GJA1):c.461C>A (p.Thr154Asn)	GJA1	Likely pathogenic	criteria provided, single submitter
2734938	NM_000165.5(GJA1):c.121G>C (p.Val41Leu)	GJA1	Likely pathogenic	criteria provided, single submitter
2734939	NM_000165.5(GJA1):c.226C>T (p.Arg76Cys)	GJA1	Likely pathogenic	criteria provided, single submitter
4747539	NM_000165.5(GJA1):c.402G>T (p.Lys134Asn)	GJA1	Likely pathogenic	criteria provided, single submitter
4747540	NM_000165.5(GJA1):c.442C>G (p.Arg148Gly)	GJA1	Likely pathogenic	criteria provided, single submitter
941061	NM_000165.5(GJA1):c.577C>G (p.Pro193Ala)	GJA1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 25 · Orphanet: 12 · 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
GJA1	Definitive	Autosomal dominant	oculodentodigital dysplasia	25

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GJA1	Orphanet:1010	Autosomal dominant palmoplantar keratoderma and congenital alopecia
GJA1	Orphanet:1522	Craniometaphyseal dysplasia
GJA1	Orphanet:2248	Hypoplastic left heart syndrome
GJA1	Orphanet:2710	Oculodentodigital dysplasia
GJA1	Orphanet:317	Erythrokeratodermia variabilis
GJA1	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
GJA1	Orphanet:93404	Syndactyly type 3
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

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
GJA1	HGNC:4274	ENSG00000152661	P17302	Gap junction alpha-1 protein	gencc,clinvar
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GJA1	Gap junction alpha-1 protein	Structural component of the gap junction, a specialized intercellular structure consisting of a cluster of closely packed pairs of transmembrane channels, the connexons, that allow passage of small molecules and electrical signals between…
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GJA1	Other/Unknown	no		Connexin, Connexin43, Connexin_N
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal motor nucleus of vagus nerve	1
hair follicle	1
lateral globus pallidus	1
adenohypophysis	1
male germ line stem cell (sensu Vertebrata) in testis	1
pituitary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GJA1	292	ubiquitous	marker	lateral globus pallidus, dorsal motor nucleus of vagus nerve, hair follicle
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GJA1	4,942
COL11A2	1,583

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GJA1	P17302	19

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL11A2	P13942	50.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
Oligomerization of connexins into connexons	1	1903.3×	0.003	GJA1
Transport of connexins along the secretory pathway	1	1903.3×	0.003	GJA1
Regulation of gap junction activity	1	1903.3×	0.003	GJA1
SARS-CoV-2 targets PDZ proteins in cell-cell junction	1	1142.0×	0.004	GJA1
Formation of annular gap junctions	1	519.1×	0.006	GJA1
Gap junction degradation	1	475.8×	0.006	GJA1
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	335.9×	0.008	GJA1
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	271.9×	0.008	GJA1
MET activates PTK2 signaling	1	190.3×	0.010	COL11A2
Gap junction assembly	1	146.4×	0.012	GJA1
Collagen chain trimerization	1	129.8×	0.012	COL11A2
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.012	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.012	COL11A2
RHOJ GTPase cycle	1	100.2×	0.012	GJA1
RHOQ GTPase cycle	1	90.6×	0.012	GJA1
Collagen degradation	1	87.8×	0.012	COL11A2
Collagen biosynthesis and modifying enzymes	1	85.2×	0.012	COL11A2
Non-integrin membrane-ECM interactions	1	77.2×	0.013	COL11A2

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
microtubule-based transport	1	8426.0×	0.002	GJA1
positive regulation of mesodermal cell differentiation	1	8426.0×	0.002	GJA1
negative regulation of gonadotropin secretion	1	4213.0×	0.003	GJA1
positive regulation of morphogenesis of an epithelium	1	2808.7×	0.003	GJA1
cell communication by electrical coupling	1	2106.5×	0.003	GJA1
soft palate development	1	1685.2×	0.004	COL11A2
negative regulation of trophoblast cell migration	1	1203.7×	0.004	GJA1
gap junction assembly	1	1053.2×	0.004	GJA1
glutamate secretion	1	842.6×	0.004	GJA1
atrial cardiac muscle cell action potential	1	842.6×	0.004	GJA1
export across plasma membrane	1	842.6×	0.004	GJA1
cell communication by electrical coupling involved in cardiac conduction	1	702.2×	0.004	GJA1
cardiac conduction system development	1	526.6×	0.005	GJA1
bone remodeling	1	468.1×	0.005	GJA1
xenobiotic transport	1	421.3×	0.006	GJA1
positive regulation of stem cell proliferation	1	263.3×	0.008	GJA1
establishment of mitotic spindle orientation	1	240.7×	0.008	GJA1
maintenance of blood-brain barrier	1	240.7×	0.008	GJA1
positive regulation of vascular associated smooth muscle cell proliferation	1	216.1×	0.009	GJA1
cellular response to amyloid-beta	1	195.9×	0.009	GJA1
bone development	1	138.1×	0.012	GJA1
cartilage development	1	125.8×	0.013	COL11A2
roof of mouth development	1	123.9×	0.013	COL11A2
collagen fibril organization	1	112.3×	0.013	COL11A2
monoatomic ion transmembrane transport	1	104.0×	0.014	GJA1
positive regulation of cold-induced thermogenesis	1	81.8×	0.017	GJA1
negative regulation of cell growth	1	72.0×	0.018	GJA1
skeletal system development	1	62.9×	0.020	COL11A2
intracellular protein localization	1	52.3×	0.024	GJA1
sensory perception of sound	1	50.5×	0.024	COL11A2

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
GJA1	KANAMYCIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GJA1	1	4
COL11A2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
KANAMYCIN	4	GJA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GJA1	4	Binding:4

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

1 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)
KANAMYCIN	4	GJA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GJA1
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	COL11A2

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)
COL11A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.