Leukoencephalopathy with calcifications and cysts

Summary

Leukoencephalopathy with calcifications and cysts (MONDO:0013803) is a disease caused by SNORD118 (GenCC Strong), with 4 cohort genes and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SNORD118 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 56
• Phenotypes (HPO): 27
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0002352	Leukoencephalopathy	Very frequent (80-99%)
HP:0002514	Cerebral calcification	Very frequent (80-99%)
HP:0010576	Intracranial cystic lesion	Very frequent (80-99%)
HP:0000712	Emotional lability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001268	Mental deterioration	Frequent (30-79%)
HP:0002135	Basal ganglia calcification	Frequent (30-79%)
HP:0002461	Dense calcifications in the cerebellar dentate nucleus	Frequent (30-79%)
HP:0007229	Intracerebral periventricular calcifications	Frequent (30-79%)
HP:0007256	Abnormal pyramidal sign	Frequent (30-79%)
HP:0007346	Subcortical white matter calcifications	Frequent (30-79%)
HP:0100320	Rosenthal fibers	Frequent (30-79%)
HP:0100543	Cognitive impairment	Frequent (30-79%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001342	Cerebral hemorrhage	Occasional (5-29%)
HP:0002516	Increased intracranial pressure	Occasional (5-29%)
HP:0007291	Posterior fossa cyst	Occasional (5-29%)
HP:0011153	Focal motor seizure	Occasional (5-29%)
HP:0002059	Cerebral atrophy	Excluded (0%)
HP:0000725	Psychotic episodes	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	leukoencephalopathy with calcifications and cysts
Mondo ID	MONDO:0013803
MeSH	C000598644
OMIM	614561
Orphanet	542310
UMLS	C3281200
MedGen	482830
GARD	0010732
Is cancer (heuristic)	no

Also known as: LCC · leukoencephalopathy, brain calcifications, and cysts

Data availability: 56 ClinVar variants · 4 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 › leukoencephalopathy with calcifications and cysts

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, 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, 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

56 retrieved; paginated sample, class counts are floors:

21 pathogenic, 16 uncertain significance, 12 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
929296	NC_000017.11:g.8076912C>T	ALOX12B	Pathogenic	no assertion criteria provided
929297	NC_000017.11:g.8076886_8076914dup	ALOX12B	Pathogenic	no assertion criteria provided
929298	NC_000017.11:g.8076955_8076960del	ALOX12B	Pathogenic	no assertion criteria provided
430703	NM_183065.4(TMEM107):c.134A>G (p.Glu45Gly)	LOC105371520	Pathogenic	criteria provided, single submitter
265784	NC_000017.11:g.8173637_8173642del	LOC130060223	Pathogenic	no assertion criteria provided
929299	NC_000017.11:g.8173378_8173659del	LOC130060223	Pathogenic	no assertion criteria provided
265785	NC_000017.11:g.8173569_8173597dup	SNORD118	Pathogenic	no assertion criteria provided
265788	NM_183065.4(TMEM107):c.*759C>T	SNORD118	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929264	NC_000017.11:g.8173448G>C	SNORD118	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929266	NR_033294.2(SNORD118):n.131C>A	SNORD118	Pathogenic	no assertion criteria provided
929267	NR_033294.2(SNORD118):n.130T>C	SNORD118	Pathogenic	no assertion criteria provided
929272	NR_033294.2(SNORD118):n.100T>G	SNORD118	Pathogenic	no assertion criteria provided
929274	NR_033294.2(SNORD118):n.81G>C	SNORD118	Pathogenic	no assertion criteria provided
929279	NR_033294.2(SNORD118):n.73T>G	SNORD118	Pathogenic	no assertion criteria provided
929280	NR_033294.2(SNORD118):n.72A>G	SNORD118	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929283	NR_033294.2(SNORD118):n.60_61insT	SNORD118	Pathogenic	no assertion criteria provided
929284	NR_033294.2(SNORD118):n.60G>C	SNORD118	Pathogenic	no assertion criteria provided
929285	NR_033294.2(SNORD118):n.59T>G	SNORD118	Pathogenic	no assertion criteria provided
929286	NR_033294.2(SNORD118):n.58dup	SNORD118	Pathogenic	no assertion criteria provided
929287	NR_033294.2(SNORD118):n.57G>T	SNORD118	Pathogenic	no assertion criteria provided
929288	NR_033294.2(SNORD118):n.56dup	SNORD118	Pathogenic	no assertion criteria provided
929292	NR_033294.2(SNORD118):n.8G>C	SNORD118	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929294	NR_033294.2(SNORD118):n.3C>A	SNORD118	Pathogenic	no assertion criteria provided
929295	NR_033294.2(SNORD118):n.2T>C	SNORD118	Pathogenic	no assertion criteria provided
929290	NR_033294.2(SNORD118):n.39G>C	TMEM107	Pathogenic	criteria provided, multiple submitters, no conflicts
2683898	GRCh38/hg38 17p13.1(chr17:8171228-8185326)x1	BORCS6	Likely pathogenic	criteria provided, single submitter
929273	NR_033294.2(SNORD118):n.82A>G	SNORD118	Likely pathogenic	criteria provided, multiple submitters, no conflicts
929291	NR_033294.2(SNORD118):n.39G>T	TMEM107	Likely pathogenic	criteria provided, single submitter
1922719	NR_033294.2(SNORD118):n.66A>C	SNORD118	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522851	NR_033294.2(SNORD118):n.3C>T	SNORD118	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 5 · 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
SNORD118	Strong	Autosomal recessive	leukoencephalopathy with calcifications and cysts	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SNORD118	Orphanet:542310	Leukoencephalopathy with calcifications and cysts
TMEM107	Orphanet:564	Meckel syndrome
ALOX12B	Orphanet:281122	Self-improving collodion baby
ALOX12B	Orphanet:313	Lamellar ichthyosis
ALOX12B	Orphanet:79394	Congenital ichthyosiform erythroderma

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SNORD118	HGNC:32952	ENSG00000200463		small nucleolar RNA, C/D box 118	gencc,clinvar
BORCS6	HGNC:25939	ENSG00000196544	Q96GS4	BLOC-1-related complex subunit 6	clinvar
TMEM107	HGNC:28128	ENSG00000179029	Q6UX40	Transmembrane protein 107	clinvar
ALOX12B	HGNC:430	ENSG00000179477	O75342	Arachidonate 12-lipoxygenase, 12R-type	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BORCS6	BLOC-1-related complex subunit 6	As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery.
TMEM107	Transmembrane protein 107	Plays a role in cilia formation and embryonic patterning.
ALOX12B	Arachidonate 12-lipoxygenase, 12R-type	Catalyzes the regio and stereo-specific incorporation of a single molecule of dioxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · 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
Enzyme (other)	1	3.0×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SNORD118	Other/Unknown	no
BORCS6	Other/Unknown	no		BORCS6, BORCS6_C
TMEM107	Other/Unknown	no		TMEM107
ALOX12B	Enzyme (other)	yes	1.13.11.31	LipOase, PLAT/LH2_dom, LipOase_mml

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
kidney	1
sural nerve	1
granulocyte	1
olfactory bulb	1
type B pancreatic cell	1
bronchial epithelial cell	1
bronchus	1
right uterine tube	1
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SNORD118	81	ubiquitous	yes	sural nerve, kidney, adult mammalian kidney
BORCS6	219	ubiquitous	yes	type B pancreatic cell, olfactory bulb, granulocyte
TMEM107	240	ubiquitous	marker	bronchial epithelial cell, bronchus, right uterine tube
ALOX12B	168	broad	yes	skin of leg, skin of abdomen, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALOX12B	1,126
BORCS6	954
TMEM107	656
SNORD118	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMEM107	Q6UX40	94.21
ALOX12B	O75342	92.07
BORCS6	Q96GS4	66.53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 4 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
Synthesis of 12-eicosatetraenoic acid derivatives	1	1631.4×	0.003	ALOX12B
Arachidonate metabolism	1	571.0×	0.004	ALOX12B
Fatty acid metabolism	1	131.3×	0.013	ALOX12B
Metabolism of lipids	1	31.6×	0.040	ALOX12B
Metabolism	1	11.6×	0.086	ALOX12B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
detection of nodal flow	1	1872.4×	0.004	TMEM107
protein lipidation	1	1123.5×	0.004	ALOX12B
positive regulation of mucus secretion	1	1123.5×	0.004	ALOX12B
neural tube patterning	1	936.2×	0.004	TMEM107
protein localization to ciliary transition zone	1	802.5×	0.004	TMEM107
lipid oxidation	1	702.2×	0.004	ALOX12B
hepoxilin biosynthetic process	1	702.2×	0.004	ALOX12B
regulation of lysosome size	1	624.1×	0.004	BORCS6
craniofacial suture morphogenesis	1	561.7×	0.004	TMEM107
lipoxygenase pathway	1	510.7×	0.004	ALOX12B
regulation of endosome size	1	510.7×	0.004	BORCS6
organelle transport along microtubule	1	401.2×	0.005	BORCS6
sphingolipid metabolic process	1	330.4×	0.006	ALOX12B
linoleic acid metabolic process	1	234.1×	0.008	ALOX12B
lysosome localization	1	175.5×	0.009	BORCS6
arachidonate metabolic process	1	160.5×	0.010	ALOX12B
establishment of skin barrier	1	151.8×	0.010	ALOX12B
ceramide biosynthetic process	1	140.4×	0.010	ALOX12B
embryonic digit morphogenesis	1	100.3×	0.013	TMEM107
non-motile cilium assembly	1	96.8×	0.013	TMEM107
roof of mouth development	1	82.6×	0.014	TMEM107
regulation of gene expression	1	27.8×	0.040	TMEM107
positive regulation of MAPK cascade	1	26.9×	0.040	ALOX12B
cilium assembly	1	24.5×	0.042	TMEM107
positive regulation of gene expression	1	12.9×	0.075	ALOX12B

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SNORD118	0	0
BORCS6	0	0
TMEM107	0	0
ALOX12B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALOX12B	1.13.11.31	arachidonate 12-lipoxygenase

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	0
D	Druggable family + AlphaFold only, no drug	1	ALOX12B
E	Difficult family or no structure, no drug	3	SNORD118, BORCS6, TMEM107

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)
SNORD118	0	—
BORCS6	0	—
TMEM107	0	—
ALOX12B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies