Hypomyelinating leukodystrophy 10

Summary

Hypomyelinating leukodystrophy 10 (MONDO:0014632) is a disease caused by PYCR2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PYCR2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 43
• Phenotypes (HPO): 62

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		18	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000253	Progressive microcephaly	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001344	Absent speech	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0002540	Inability to walk	Very frequent (80-99%)
HP:0011344	Severe global developmental delay	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)
HP:0000327	Hypoplasia of the maxilla	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000411	Protruding ear	Frequent (30-79%)
HP:0000414	Bulbous nose	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002013	Vomiting	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)
HP:0003429	CNS hypomyelination	Frequent (30-79%)
HP:0007258	Severe demyelination of the white matter	Frequent (30-79%)
HP:0030890	Hyperintensity of cerebral white matter on MRI	Frequent (30-79%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000233	Thin vermilion border	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000325	Triangular face	Occasional (5-29%)
HP:0000341	Narrow forehead	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000396	Overfolded helix	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000494	Downslanted palpebral fissures	Occasional (5-29%)
HP:0000565	Esotropia	Occasional (5-29%)
HP:0000582	Upslanted palpebral fissure	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000737	Irritability	Occasional (5-29%)
HP:0000768	Pectus carinatum	Occasional (5-29%)
HP:0000924	Abnormality of the skeletal system	Occasional (5-29%)
HP:0001166	Arachnodactyly	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001274	Agenesis of corpus callosum	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001347	Hyperreflexia	Occasional (5-29%)
HP:0001371	Flexion contracture	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0002069	Bilateral tonic-clonic seizure	Occasional (5-29%)
HP:0002283	Global brain atrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hypomyelinating leukodystrophy 10
Mondo ID	MONDO:0014632
OMIM	616420
Orphanet	481152
DOID	DOID:0060788
UMLS	C4225332
MedGen	904191
GARD	0025008
Is cancer (heuristic)	no

Also known as: HLD10 · hypomyelinating leukodystrophy type 10 · leukodystrophy caused by mutation in PYCR2 · leukodystrophy, hypomyelinating, 10 · leukodystrophy, hypomyelinating, type 10 · PYCR2 leukodystrophy · PYCR2-related microcephaly-progressive leukoencephalopathy

Data availability: 43 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › hypomyelinating leukodystrophy 10

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, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

43 retrieved; paginated sample, class counts are floors:

14 likely pathogenic, 9 uncertain significance, 7 pathogenic, 6 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 2 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323507	NM_013328.4(PYCR2):c.354dup (p.Arg119fs)	PYCR2	Pathogenic	criteria provided, single submitter
1334633	NM_013328.4(PYCR2):c.676C>T (p.Gln226Ter)	PYCR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1357942	NM_013328.4(PYCR2):c.309del (p.Val104fs)	PYCR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1905643	NM_013328.4(PYCR2):c.252del (p.Asp85fs)	PYCR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
192394	NM_013328.4(PYCR2):c.751C>T (p.Arg251Cys)	PYCR2	Pathogenic	no assertion criteria provided
254247	NM_013328.4(PYCR2):c.796C>T (p.Arg266Ter)	PYCR2	Pathogenic	criteria provided, multiple submitters, no conflicts
254250	NM_013328.4(PYCR2):c.694T>G (p.Cys232Gly)	PYCR2	Pathogenic	no assertion criteria provided
286401	NM_013328.4(PYCR2):c.757_758dup (p.Leu254fs)	PYCR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775353	NM_013328.4(PYCR2):c.746dup (p.Phe250fs)	PYCR2	Pathogenic	criteria provided, single submitter
3775786	NM_013328.4(PYCR2):c.67+2C>T	PYCR2	Pathogenic	criteria provided, single submitter
4847146	NM_013328.4(PYCR2):c.619dup (p.Ala207fs)	PYCR2	Pathogenic	criteria provided, single submitter
1324974	NM_013328.4(PYCR2):c.318+1G>A	PYCR2	Likely pathogenic	criteria provided, single submitter
192393	NM_013328.4(PYCR2):c.355C>T (p.Arg119Cys)	PYCR2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
254248	NM_013328.4(PYCR2):c.773T>C (p.Val258Ala)	PYCR2	Likely pathogenic	criteria provided, single submitter
2682490	NM_013328.4(PYCR2):c.577G>A (p.Val193Met)	PYCR2	Likely pathogenic	criteria provided, single submitter
3255597	NM_013328.4(PYCR2):c.398_399del (p.Thr133fs)	PYCR2	Likely pathogenic	criteria provided, single submitter
3255598	NM_013328.4(PYCR2):c.686A>G (p.Asp229Gly)	PYCR2	Likely pathogenic	criteria provided, single submitter
3731482	NM_013328.4(PYCR2):c.633+1G>A	PYCR2	Likely pathogenic	criteria provided, single submitter
429628	NM_013328.4(PYCR2):c.356G>A (p.Arg119His)	PYCR2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
436454	NM_013328.4(PYCR2):c.139-2A>C	PYCR2	Likely pathogenic	criteria provided, single submitter
545033	NM_013328.4(PYCR2):c.138+1G>T	PYCR2	Likely pathogenic	criteria provided, single submitter
800754	NM_013328.4(PYCR2):c.529G>A (p.Gly177Arg)	PYCR2	Likely pathogenic	criteria provided, single submitter
872904	NM_013328.4(PYCR2):c.257T>G (p.Val86Gly)	PYCR2	Likely pathogenic	criteria provided, single submitter
872905	NM_013328.4(PYCR2):c.400G>A (p.Val134Met)	PYCR2	Likely pathogenic	criteria provided, single submitter
929953	NM_013328.4(PYCR2):c.402_403del (p.Tyr135fs)	PYCR2	Likely pathogenic	criteria provided, single submitter
489137	NM_013328.4(PYCR2):c.319-1G>C	MIR6741	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1188580	NM_013328.4(PYCR2):c.40G>C (p.Ala14Pro)	PYCR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
254249	NM_013328.4(PYCR2):c.595C>T (p.Arg199Trp)	PYCR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
391197	NM_013328.4(PYCR2):c.160C>T (p.Arg54Cys)	PYCR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992852	NM_013328.4(PYCR2):c.647T>G (p.Met216Arg)	PYCR2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
PYCR2	Definitive	Autosomal recessive	hypomyelinating leukodystrophy 10	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PYCR2	Orphanet:2512	Autosomal recessive primary microcephaly
PYCR2	Orphanet:481152	PYCR2-related microcephaly-progressive leukoencephalopathy

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PYCR2	HGNC:30262	ENSG00000143811	Q96C36	Pyrroline-5-carboxylate reductase 2	gencc,clinvar
MIR6741	HGNC:50004	ENSG00000284519		microRNA 6741	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PYCR2	Pyrroline-5-carboxylate reductase 2	Oxidoreductase that catalyzes the last step in proline biosynthesis, which corresponds to the reduction of pyrroline-5-carboxylate to L-proline using NAD(P)H.

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)
PYCR2	Other/Unknown	no		Pyrroline-COOH_reductase, 6-PGluconate_DH-like_C_sf, P5C_Rdtase_cat_N
MIR6741	Other/Unknown	no

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)	1
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac muscle of right atrium	1
left ventricle myocardium	1
right uterine tube	1
blood	1
gastrocnemius	1
omental fat pad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PYCR2	251	ubiquitous	marker	cardiac muscle of right atrium, right uterine tube, left ventricle myocardium
MIR6741	5		yes	blood, gastrocnemius, omental fat pad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PYCR2	1,728
MIR6741	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PYCR2	Q96C36	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glutamate and glutamine metabolism	1	815.7×	0.001	PYCR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
L-proline biosynthetic process	1	2808.7×	7e-04	PYCR2
cellular response to oxidative stress	1	154.6×	0.006	PYCR2

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
PYCR2	0	0
MIR6741	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
PYCR2	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PYCR2, MIR6741

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)
PYCR2	2	—
MIR6741	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.