Behr syndrome

Summary

Behr syndrome (MONDO:0008858) is a disease caused by OPA1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: OPA1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Behr syndrome
Mondo ID	MONDO:0008858
MeSH	C537669
OMIM	210000
Orphanet	1239
DOID	DOID:0111580
NCIT	C177251
SNOMED CT	718221007
UMLS	C0221061
MedGen	66358
GARD	0000849
Is cancer (heuristic)	no

Also known as: Behr syndrome · BEHRS · optic atrophy in early childhood, associated with ataxia, spasticity, intellectual disability, and posterior column sensory loss · optic atrophy in early childhood, associated with ataxia, spasticity, mental retardation, and posterior column sensory loss · optic atrophy, infantile hereditary, Behr complicated form of

Data availability: 34 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

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 › Behr syndrome

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, 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, 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

34 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 7 conflicting classifications of pathogenicity, 4 pathogenic, 4 likely pathogenic, 4 benign, 3 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
225123	NM_130837.3(OPA1):c.1870+1G>T	LOC126806913	Pathogenic	no assertion criteria provided
195896	NM_130837.3(OPA1):c.2734C>T (p.Arg912Ter)	OPA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2003096	NM_130837.3(OPA1):c.2885_2983+8del	OPA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225121	NM_130837.3(OPA1):c.2635C>T (p.Arg879Ter)	OPA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
500848	NM_130837.3(OPA1):c.1389dup (p.Gly464fs)	OPA1	Pathogenic	criteria provided, multiple submitters, no conflicts
5082	NM_130837.3(OPA1):c.2873_2876del	OPA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973235	NM_130837.3(OPA1):c.2287del (p.Ser763fs)	OPA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2585301	NM_130837.3(OPA1):c.2937_2938del (p.Lys979fs)	OPA1	Likely pathogenic	criteria provided, single submitter
3767222	NM_130837.3(OPA1):c.370G>T (p.Asp124Tyr)	OPA1	Likely pathogenic	criteria provided, single submitter
3776054	NM_130837.3(OPA1):c.1935+1G>T	OPA1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
930410	NM_130837.3(OPA1):c.2489G>A (p.Trp830Ter)	OPA1	Likely pathogenic	criteria provided, single submitter
214895	NM_130837.3(OPA1):c.3027A>C (p.Glu1009Asp)	OPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
214916	NM_130837.3(OPA1):c.113_130del (p.Arg38_Ser43del)	OPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
344482	NM_130837.3(OPA1):c.653C>T (p.Ser218Phe)	OPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
432856	NM_130837.3(OPA1):c.2617C>T (p.Arg873Trp)	OPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
502104	NM_130837.3(OPA1):c.245A>G (p.Tyr82Cys)	OPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
50866	NM_130837.3(OPA1):c.1311A>G (p.Ile437Met)	OPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930477	NM_130837.3(OPA1):c.1626A>G (p.Glu542=)	OPA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
930631	NM_130837.3(OPA1):c.1811C>T (p.Ser604Leu)	LOC126806913	Uncertain significance	criteria provided, multiple submitters, no conflicts
1983543	NM_130837.3(OPA1):c.1345A>G (p.Met449Val)	OPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
225122	NM_130837.3(OPA1):c.1369G>A (p.Val457Met)	OPA1	Uncertain significance	criteria provided, single submitter
3242088	NM_130837.3(OPA1):c.1476A>C (p.Gln492His)	OPA1	Uncertain significance	criteria provided, single submitter
3242089	NM_130837.3(OPA1):c.267G>A (p.Trp89Ter)	OPA1	Uncertain significance	criteria provided, single submitter
3383279	NM_130837.3(OPA1):c.2345A>G (p.His782Arg)	OPA1	Uncertain significance	criteria provided, single submitter
3589112	NM_130837.3(OPA1):c.1049G>A (p.Gly350Glu)	OPA1	Uncertain significance	criteria provided, single submitter
3680777	NM_130837.3(OPA1):c.1728G>T (p.Glu576Asp)	OPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
432381	NM_130837.3(OPA1):c.2429G>A (p.Arg810His)	OPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
586200	NM_130837.3(OPA1):c.1016C>T (p.Thr339Met)	OPA1	Uncertain significance	criteria provided, multiple submitters, no conflicts
997638	NM_130837.3(OPA1):c.861C>G (p.Ile287Met)	OPA1	Uncertain significance	criteria provided, single submitter
931270	NM_130837.3(OPA1):c.2924A>G (p.Asp975Gly)	OPA1	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 32 · Orphanet: 8 · 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
MED12	Strong	Autosomal recessive	Behr syndrome	21
OPA1	Strong	Autosomal recessive	Behr syndrome	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MED12	Orphanet:1415	Hardikar syndrome
MED12	Orphanet:293707	Blepharophimosis-intellectual disability syndrome, MKB type
MED12	Orphanet:776	Lujan-Fryns syndrome
MED12	Orphanet:777	X-linked non-syndromic intellectual disability
MED12	Orphanet:93932	FG syndrome type 1
OPA1	Orphanet:1215	Autosomal dominant optic atrophy plus syndrome
OPA1	Orphanet:1239	Behr syndrome
OPA1	Orphanet:98673	Autosomal dominant optic atrophy, classic form

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
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	gencc,clinvar
OPA1	HGNC:8140	ENSG00000198836	O60313	Dynamin-like GTPase OPA1, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MED12	Mediator of RNA polymerase II transcription subunit 12	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
OPA1	Dynamin-like GTPase OPA1, mitochondrial	Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain function.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
OPA1	Enzyme (other)	yes	3.6.5.5	Dynamin_GTPase, Dynamin, P-loop_NTPase

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
left ovary	1
right adrenal gland	1
right adrenal gland cortex	1
adrenal tissue	1
calcaneal tendon	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
OPA1	288	ubiquitous	marker	adrenal tissue, calcaneal tendon, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MED12	3,322
OPA1	2,630

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OPA1	O60313	11
MED12	Q93074	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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
Regulation of Apoptosis	1	951.7×	0.023	OPA1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	107.7×	0.038	MED12
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	98.5×	0.038	MED12
Respiratory Syncytial Virus Infection Pathway	1	98.5×	0.038	MED12
RSV-host interactions	1	78.2×	0.038	MED12
Adipogenesis	1	78.2×	0.038	MED12
Epigenetic regulation by WDR5-containing histone modifying complexes	1	77.2×	0.038	MED12
Regulation of lipid metabolism by PPARalpha	1	70.5×	0.038	MED12
Transcriptional regulation of white adipocyte differentiation	1	64.9×	0.038	MED12
Mitochondrial protein degradation	1	57.1×	0.038	OPA1
PPARA activates gene expression	1	47.2×	0.042	MED12
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	41.4×	0.044	MED12
Epigenetic regulation of gene expression	1	35.7×	0.047	MED12
Metabolism of lipids	1	15.8×	0.094	MED12
Viral Infection Pathways	1	15.4×	0.094	MED12
Infectious disease	1	12.4×	0.109	MED12
RNA Polymerase II Transcription	1	11.3×	0.112	MED12
Gene expression (Transcription)	1	8.9×	0.133	MED12
Generic Transcription Pathway	1	7.5×	0.147	MED12
Developmental Biology	1	7.2×	0.147	MED12
Disease	1	6.5×	0.154	MED12
Metabolism	1	5.8×	0.165	MED12

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
neural tube closure	2	187.2×	1e-03	MED12, OPA1
mitochondrial inner membrane fusion	1	8426.0×	0.002	OPA1
axis elongation involved in somitogenesis	1	2808.7×	0.003	MED12
membrane tubulation	1	2808.7×	0.003	OPA1
positive regulation of T-helper 17 cell lineage commitment	1	1053.2×	0.005	OPA1
embryonic neurocranium morphogenesis	1	936.2×	0.005	MED12
peroxisome fission	1	766.0×	0.005	OPA1
axonal transport of mitochondrion	1	702.2×	0.005	OPA1
GTP metabolic process	1	561.7×	0.005	OPA1
mitochondrial fission	1	526.6×	0.005	OPA1
Schwann cell development	1	526.6×	0.005	MED12
cristae formation	1	526.6×	0.005	OPA1
inner mitochondrial membrane organization	1	421.3×	0.005	OPA1
mitochondrial fusion	1	421.3×	0.005	OPA1
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	421.3×	0.005	OPA1
negative regulation of release of cytochrome c from mitochondria	1	401.2×	0.005	OPA1
embryonic brain development	1	401.2×	0.005	MED12
post-anal tail morphogenesis	1	366.4×	0.005	MED12
protein complex oligomerization	1	337.0×	0.005	OPA1
endoderm development	1	312.1×	0.005	MED12
oligodendrocyte development	1	300.9×	0.005	MED12
positive regulation of interleukin-17 production	1	300.9×	0.005	OPA1
spinal cord development	1	255.3×	0.006	MED12
Wnt signaling pathway, planar cell polarity pathway	1	227.7×	0.006	MED12
cellular senescence	1	147.8×	0.009	OPA1
positive regulation of transcription initiation by RNA polymerase II	1	135.9×	0.010	MED12
somatic stem cell population maintenance	1	123.9×	0.010	MED12
mitochondrion organization	1	75.9×	0.016	OPA1
visual perception	1	39.8×	0.029	OPA1
heart development	1	39.4×	0.029	MED12

Therapeutics

Drug target analysis

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

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
OPA1	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OPA1	2	4
MED12	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	OPA1
TIVANTINIB	3	OPA1
MOLIBRESIB	2	MED12

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MED12	6	Binding:6
OPA1	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
OPA1	3.6.5.5	dynamin GTPase

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

3 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)
MOMELOTINIB	4	OPA1
TIVANTINIB	3	OPA1
MOLIBRESIB	2	MED12

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	OPA1
B	Phased (≥1) drug, not yet approved	1	MED12
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.