Familial congenital mirror movements

Summary

Familial congenital mirror movements (MONDO:0016558) is a disease with 4 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• Phenotypes (HPO): 14
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		75	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0001335	Bimanual synkinesia	Frequent (30-79%)
HP:0002312	Clumsiness	Frequent (30-79%)
HP:0002492	Morphological abnormality of the corticospinal tract	Frequent (30-79%)
HP:0003388	Easy fatigability	Frequent (30-79%)
HP:0007010	Poor fine motor coordination	Frequent (30-79%)
HP:0100022	Abnormality of movement	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0025101	Dysgenesis of the hippocampus	Occasional (5-29%)
HP:0000044	Hypogonadotropic hypogonadism	Very rare (<1-4%)
HP:0001256	Intellectual disability, mild	Very rare (<1-4%)
HP:0002949	Fused cervical vertebrae	Very rare (<1-4%)
HP:0100021	Cerebral palsy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	familial congenital mirror movements
Mondo ID	MONDO:0016558
OMIM	157600
Orphanet	238722
DOID	DOID:0111153
ICD-11	1966778637
SNOMED CT	229247004
UMLS	C0454455
MedGen	473166
GARD	0012551
Is cancer (heuristic)	no

Also known as: bimanual synkinesis · CMM · congenital mirror movement disorder · congenital mirror movements · familial congenital controlateral synkinesia · familial congenital mirror movements · hereditary congenital controlateral synkinesia · hereditary congenital mirror movements · isolated congenital controlateral synkinesia · isolated congenital mirror movements

Data availability: 4 GenCC gene-disease records.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › familial congenital mirror movements

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, 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

Subtypes (4): mirror movements 2, mirror movements 3, mirror movements 4, mirror movements 1 and/or agenesis of the corpus callosum

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 29 · 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
DCC	Definitive	Autosomal dominant	mirror movements 1	12
NTN1	Strong	Autosomal dominant	mirror movements 4	5
RAD51	Strong	Autosomal dominant	mirror movements 2	10
DNAL4	Supportive	Autosomal dominant	familial congenital mirror movements	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCC	Orphanet:238722	Familial congenital mirror movements
DCC	Orphanet:2744	Horizontal gaze palsy with progressive scoliosis
DCC	Orphanet:478	Kallmann syndrome
DNAL4	Orphanet:238722	Familial congenital mirror movements
NTN1	Orphanet:238722	Familial congenital mirror movements
RAD51	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
RAD51	Orphanet:238722	Familial congenital mirror movements
RAD51	Orphanet:84	Fanconi anemia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	gencc
DNAL4	HGNC:2955	ENSG00000100246	O96015	Dynein axonemal light chain 4	gencc
NTN1	HGNC:8029	ENSG00000065320	O95631	Netrin-1	gencc
RAD51	HGNC:9817	ENSG00000051180	Q06609	DNA repair protein RAD51 homolog 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
DNAL4	Dynein axonemal light chain 4	Force generating protein of respiratory cilia.
NTN1	Netrin-1	Netrins control guidance of CNS commissural axons and peripheral motor axons.
RAD51	DNA repair protein RAD51 homolog 1	Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Antibody/Immunoglobulin	1	7.3×	0.390
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
DNAL4	Other/Unknown	no		Dynein_light_chain_typ-1/2, DLC_sf
NTN1	Other/Unknown	no		Netrin_domain, LE_dom, Laminin_N
RAD51	Transcription factor	no	3.6.4.B7	AAA+_ATPase, DNA_repair_Rad51/TF_NusA_a-hlx, DNA_recomb/repair_Rad51

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
cortical plate	1
right uterine tube	1
lower esophagus muscularis layer	1
mucosa of stomach	1
right atrium auricular region	1
buccal mucosa cell	1
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCC	154	broad	marker	cortical plate, right testis, left testis
DNAL4	207	tissue_specific	marker	left testis, right testis, right uterine tube
NTN1	218	broad	marker	mucosa of stomach, right atrium auricular region, lower esophagus muscularis layer
RAD51	193	ubiquitous	marker	primordial germ cell in gonad, buccal mucosa cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAD51	6,465
NTN1	2,072
DNAL4	1,616
DCC	1,333

Intra-cohort edges

A	B	Sources
DCC	NTN1	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAD51	Q06609	52
DCC	P43146	9
NTN1	O95631	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DNAL4	O96015	90.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DSCAM interactions	2	1142.0×	2e-05	DCC, NTN1
Netrin mediated repulsion signals	2	634.4×	4e-05	DCC, NTN1
Role of second messengers in netrin-1 signaling	2	519.1×	4e-05	DCC, NTN1
Regulation of commissural axon pathfinding by SLIT and ROBO	2	475.8×	4e-05	DCC, NTN1
DCC mediated attractive signaling	2	356.9×	6e-05	DCC, NTN1
Netrin-1 signaling	2	219.6×	1e-04	DCC, NTN1
Caspase activation via Dependence Receptors in the absence of ligand	1	285.5×	0.012	DCC
Retrograde neurotrophin signalling	1	203.9×	0.015	DNAL4
Impaired BRCA2 binding to PALB2	1	114.2×	0.019	RAD51
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	105.7×	0.019	RAD51
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	105.7×	0.019	RAD51
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	105.7×	0.019	RAD51
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	98.5×	0.019	RAD51
Homologous DNA Pairing and Strand Exchange	1	95.2×	0.019	RAD51
Impaired BRCA2 binding to RAD51	1	77.2×	0.019	RAD51
Resolution of D-loop Structures through Holliday Junction Intermediates	1	75.1×	0.019	RAD51
HDR through Single Strand Annealing (SSA)	1	73.2×	0.019	RAD51
Transcriptional Regulation by E2F6	1	73.2×	0.019	RAD51
Presynaptic phase of homologous DNA pairing and strand exchange	1	68.0×	0.019	RAD51
HDR through Homologous Recombination (HRR)	1	47.6×	0.026	RAD51
Meiotic recombination	1	32.4×	0.036	RAD51
Signaling by ROBO receptors	1	31.0×	0.036	NTN1
Axon guidance	1	11.3×	0.093	NTN1
Nervous system development	1	10.7×	0.094	NTN1
Developmental Biology	1	3.6×	0.249	NTN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
anterior/posterior axon guidance	2	1404.3×	4e-05	DCC, NTN1
response to glucoside	1	4213.0×	0.005	RAD51
regulation of glial cell migration	1	2106.5×	0.005	NTN1
mitotic recombination-dependent replication fork processing	1	2106.5×	0.005	RAD51
DNA recombinase assembly	1	1404.3×	0.005	RAD51
spinal cord ventral commissure morphogenesis	1	1404.3×	0.005	DCC
Cdc42 protein signal transduction	1	1053.2×	0.005	NTN1
dorsal/ventral axon guidance	1	1053.2×	0.005	DCC
DNA strand invasion	1	1053.2×	0.005	RAD51
chemorepulsion of axon	1	1053.2×	0.005	NTN1
chromosome organization involved in meiotic cell cycle	1	842.6×	0.005	RAD51
cellular response to cisplatin	1	842.6×	0.005	RAD51
cellular response to camptothecin	1	842.6×	0.005	RAD51
cell-cell adhesion	2	50.8×	0.005	DCC, NTN1
mitotic recombination	1	702.2×	0.005	RAD51
replication-born double-strand break repair via sister chromatid exchange	1	702.2×	0.005	RAD51
mammary gland duct morphogenesis	1	601.9×	0.006	NTN1
negative regulation of dendrite development	1	526.6×	0.006	DCC
telomere maintenance via telomere lengthening	1	468.1×	0.006	RAD51
motor neuron migration	1	421.3×	0.006	NTN1
telomere maintenance via recombination	1	383.0×	0.006	RAD51
substrate-dependent cell migration, cell extension	1	383.0×	0.006	NTN1
negative regulation of collateral sprouting	1	383.0×	0.006	DCC
cellular response to hydroxyurea	1	351.1×	0.007	RAD51
double-strand break repair involved in meiotic recombination	1	324.1×	0.007	RAD51
regulation of DNA damage checkpoint	1	280.9×	0.008	RAD51
regulation of double-strand break repair via homologous recombination	1	247.8×	0.009	RAD51
response to X-ray	1	221.7×	0.009	RAD51
glial cell proliferation	1	221.7×	0.009	NTN1
positive regulation of cell motility	1	191.5×	0.010	NTN1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 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
DCC	0	0
DNAL4	0	0
NTN1	0	0
RAD51	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
RAD51	124	Binding:116, ADMET:8
NTN1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RAD51	3.6.4.B7

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
RAD51	124

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; 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	1	DCC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	DNAL4, NTN1, RAD51

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RAD51	124	—
DCC	0	—
DNAL4	0	—
NTN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02073604	Not specified	COMPLETED	Role of the SMA During Unimanual and Bimanual Movements Preparation: the Mirror Movements Paradigm