SLC35A2-congenital disorder of glycosylation

Summary

SLC35A2-congenital disorder of glycosylation (MONDO:0010478) is a disease caused by SLC35A2 (GenCC Definitive), with 9 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLC35A2 (GenCC Definitive)
• Cohort genes: 9
• ClinVar variants: 297
• Phenotypes (HPO): 74

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000707	Abnormality of the nervous system	Very frequent (80-99%)
HP:0000924	Abnormality of the skeletal system	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002521	Hypsarrhythmia	Very frequent (80-99%)
HP:0008947	Floppy infant	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0000951	Abnormality of the skin	Frequent (30-79%)
HP:0001155	Abnormality of the hand	Frequent (30-79%)
HP:0001272	Cerebellar atrophy	Frequent (30-79%)
HP:0001531	Failure to thrive in infancy	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002086	Abnormality of the respiratory system	Frequent (30-79%)
HP:0002500	Abnormal cerebral white matter morphology	Frequent (30-79%)
HP:0002540	Inability to walk	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002715	Abnormality of the immune system	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0008936	Axial hypotonia	Frequent (30-79%)
HP:0010864	Intellectual disability, severe	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0012345	Abnormal glycosylation	Frequent (30-79%)
HP:0012348	Decreased galactosylation of N-linked protein glycosylation	Frequent (30-79%)
HP:0012363	Decreased sialylation of O-linked protein glycosylation	Frequent (30-79%)
HP:0012448	Delayed myelination	Frequent (30-79%)
HP:0012469	Infantile spasms	Frequent (30-79%)
HP:0025053	Elevated brain N-acetyl aspartate level by MRS	Frequent (30-79%)
HP:0040288	Nasogastric tube feeding	Frequent (30-79%)
HP:0045060	Aplasia/hypoplasia involving bones of the extremities	Frequent (30-79%)
HP:0100704	Cerebral visual impairment	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000474	Thickened nuchal skin fold	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000577	Exotropia	Occasional (5-29%)
HP:0000826	Precocious puberty	Occasional (5-29%)
HP:0001010	Hypopigmentation of the skin	Occasional (5-29%)
HP:0001285	Spastic tetraparesis	Occasional (5-29%)
HP:0001363	Craniosynostosis	Occasional (5-29%)
HP:0001511	Intrauterine growth retardation	Occasional (5-29%)
HP:0001627	Abnormal heart morphology	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0001840	Metatarsus adductus	Occasional (5-29%)
HP:0002059	Cerebral atrophy	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002673	Coxa valga	Occasional (5-29%)
HP:0002686	Prenatal maternal abnormality	Occasional (5-29%)
HP:0003121	Limb joint contracture	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	SLC35A2-congenital disorder of glycosylation
Mondo ID	MONDO:0010478
OMIM	300896
Orphanet	356961
DOID	DOID:0070265
UMLS	C3806688
MedGen	813018
GARD	0012403
Is cancer (heuristic)	no

Also known as: CDG syndrome type IIm · CDG-IIm · CDG2M · congenital disorder of glycosylation type 2m · congenital disorder of glycosylation type IIm · congenital disorder of glycosylation, type IIm · congenital disorder of glycosylation, type IIm, Somatic mosaicism, X-linked dominant · EIEE22 · epileptic encephalopathy, early infantile, 22 · epileptic encephalopathy, early infantile, 22; EIEE22 · SLC35A2-CDG · SLC35A2-congenital disorder of glycosylation

Data availability: 297 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › congenital disorder of glycosylation type II › SLC35A2-congenital disorder of glycosylation

Related subtypes (25): MGAT2-congenital disorder of glycosylation, leukocyte adhesion deficiency type II, SLC35A1-congenital disorder of glycosylation, MOGS-congenital disorder of glycosylation, B4GALT1-congenital disorder of glycosylation, COG7-congenital disorder of glycosylation, COG8-congenital disorder of glycosylation, COG1-congenital disorder of glycosylation, COG4-congenital disorder of glycosylation, COG5-congenital disorder of glycosylation, COG6-congenital disorder of glycosylation, TMEM165-congenital disorder of glycosylation, SLC39A8-CDG, CCDC115-CDG, TMEM199-CDG, congenital disorder of glycosylation, type IIr, congenital disorder of glycosylation, type iit, congenital disorder of glycosylation, type 2v, congenital disorder of glycosylation, type IIw, congenital disorder of glycosylation, type IIq, congenital disorder of glycosylation, type IIy, congenital disorder of glycosylation, type IIz, congenital disorder of glycosylation, type IIaa, congenital disorder of glycosylation, type IIbb, congenital disorder of glycosylation, type IIcc

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

297 retrieved; paginated sample, class counts are floors:

98 likely benign, 90 uncertain significance, 33 pathogenic, 22 benign, 20 benign/likely benign, 19 conflicting classifications of pathogenicity, 12 likely pathogenic, 2 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
267249	NM_001378743.1(CYLD):c.2299A>T (p.Lys767Ter)	CYLD	Pathogenic	criteria provided, multiple submitters, no conflicts
1064528	NM_001282648.2(SLC35A2):c.-81_202+1del	LOC130068257	Pathogenic	criteria provided, single submitter
1030061	NM_005660.3(SLC35A2):c.340A>T (p.Lys114Ter)	SLC35A2	Pathogenic	criteria provided, single submitter
1042432	NM_005660.3(SLC35A2):c.991_993del (p.Val331del)	SLC35A2	Pathogenic	criteria provided, single submitter
1064526	NM_005660.3(SLC35A2):c.426+1G>A	SLC35A2	Pathogenic	criteria provided, single submitter
1064527	NM_005660.3(SLC35A2):c.781del (p.Arg261fs)	SLC35A2	Pathogenic	criteria provided, single submitter
1064529	NM_005660.3(SLC35A2):c.601del (p.Ala201fs)	SLC35A2	Pathogenic	criteria provided, single submitter
1072202	NM_005660.3(SLC35A2):c.656_660del (p.Val218_Tyr219insTer)	SLC35A2	Pathogenic	criteria provided, single submitter
1072227	NC_000023.10:g.(?48762413)(48763384_?)del	SLC35A2	Pathogenic	criteria provided, single submitter
1072618	NM_005660.3(SLC35A2):c.327T>G (p.Tyr109Ter)	SLC35A2	Pathogenic	criteria provided, single submitter
135674	NM_005660.3(SLC35A2):c.433_434del (p.Tyr145fs)	SLC35A2	Pathogenic	no assertion criteria provided
135675	NM_005660.3(SLC35A2):c.972del (p.Phe324fs)	SLC35A2	Pathogenic	no assertion criteria provided
135676	NM_005660.3(SLC35A2):c.638C>T (p.Ser213Phe)	SLC35A2	Pathogenic	no assertion criteria provided
1449566	NM_005660.3(SLC35A2):c.385C>T (p.Gln129Ter)	SLC35A2	Pathogenic	criteria provided, single submitter
1457955	NM_005660.3(SLC35A2):c.136C>T (p.Gln46Ter)	SLC35A2	Pathogenic	criteria provided, single submitter
1686209	NM_005660.3(SLC35A2):c.1A>T (p.Met1Leu)	SLC35A2	Pathogenic	criteria provided, single submitter
2442224	NM_005660.3(SLC35A2):c.795dup (p.Gly266fs)	SLC35A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2575887	NM_005660.3(SLC35A2):c.832C>T (p.Gln278Ter)	SLC35A2	Pathogenic	criteria provided, single submitter
2772188	NM_005660.3(SLC35A2):c.68dup (p.Leu23fs)	SLC35A2	Pathogenic	criteria provided, single submitter
2850025	NM_005660.3(SLC35A2):c.92-12C>A	SLC35A2	Pathogenic	criteria provided, single submitter
2907575	NM_005660.3(SLC35A2):c.923C>T (p.Ser308Phe)	SLC35A2	Pathogenic	criteria provided, single submitter
374354	NM_005660.3(SLC35A2):c.617_620del (p.Val206fs)	SLC35A2	Pathogenic	no assertion criteria provided
392100	NM_005660.3(SLC35A2):c.1A>G (p.Met1Val)	SLC35A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
412239	NM_005660.3(SLC35A2):c.426+287_775del	SLC35A2	Pathogenic	criteria provided, single submitter
4526870	NM_005660.3(SLC35A2):c.424C>T (p.Gln142Ter)	SLC35A2	Pathogenic	criteria provided, single submitter
50363	SLC35A2:c.15_91+48delinsA	SLC35A2	Pathogenic	no assertion criteria provided
50364	NM_005660.3(SLC35A2):c.991G>A (p.Val331Ile)	SLC35A2	Pathogenic	criteria provided, multiple submitters, no conflicts
50365	NM_005660.3(SLC35A2):c.3G>A (p.Met1Ile)	SLC35A2	Pathogenic	no assertion criteria provided
541105	NM_005660.3(SLC35A2):c.348del (p.Val117fs)	SLC35A2	Pathogenic	criteria provided, single submitter
586961	NM_005660.3(SLC35A2):c.233A>G (p.Lys78Arg)	SLC35A2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 9 · 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
SLC35A2	Definitive	X-linked	SLC35A2-congenital disorder of glycosylation	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC35A2	Orphanet:268973	Isolated focal cortical dysplasia type Ia
SLC35A2	Orphanet:356961	SLC35A2-CDG
SOX11	Orphanet:1465	Coffin-Siris syndrome
CACNA1F	Orphanet:178333	Åland Islands eye disease
CACNA1F	Orphanet:1872	Cone rod dystrophy
CACNA1F	Orphanet:714070	Incomplete congenital stationary night blindness, Schubert-Bornschein type
CYLD	Orphanet:211	Familial cylindromatosis
CYLD	Orphanet:867	Familial multiple trichoepithelioma
AKAP4	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC35A2	HGNC:11022	ENSG00000102100	P78381	UDP-galactose translocator	gencc,clinvar
SOX11	HGNC:11191	ENSG00000176887	P35716	Transcription factor SOX-11	clinvar
CACNA1F	HGNC:1393	ENSG00000102001	O60840	Voltage-dependent L-type calcium channel subunit alpha-1F	clinvar
CCNB3	HGNC:18709	ENSG00000147082	Q8WWL7	G2/mitotic-specific cyclin-B3	clinvar
NDUFA12	HGNC:23987	ENSG00000184752	Q9UI09	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12	clinvar
CYLD	HGNC:2584	ENSG00000083799	Q9NQC7	Ubiquitin carboxyl-terminal hydrolase CYLD	clinvar
CCDC120	HGNC:28910	ENSG00000147144	Q96HB5	Coiled-coil domain-containing protein 120	clinvar
AKAP4	HGNC:374	ENSG00000147081	Q5JQC9	A-kinase anchor protein 4	clinvar
ERAS	HGNC:5174	ENSG00000187682	Q7Z444	GTPase ERas	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC35A2	UDP-galactose translocator	Transports uridine diphosphate galactose (UDP-galactose) from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges UDP-galactose for UMP.
SOX11	Transcription factor SOX-11	Transcription factor that acts as a transcriptional activator.
CACNA1F	Voltage-dependent L-type calcium channel subunit alpha-1F	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
CCNB3	G2/mitotic-specific cyclin-B3	Cyclins are positive regulatory subunits of the cyclin-dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle, notably via their destruction during cell division.
NDUFA12	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	Deubiquitinase that specifically cleaves ‘Lys-63’- and linear ‘Met-1’-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-induced necroptosis.
CCDC120	Coiled-coil domain-containing protein 120	Centriolar protein required for centriole subdistal appendage assembly and microtubule anchoring in interphase cells.
AKAP4	A-kinase anchor protein 4	Major structural component of sperm fibrous sheath.
ERAS	GTPase ERas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.22

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
Ion channel	1	12.4×	0.312
Protease	1	4.1×	0.441
Other/Unknown	6	1.2×	0.507
Transcription factor	1	0.9×	0.687

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC35A2	Other/Unknown	no		Nuc_sug_transpt, EmrE-like
SOX11	Transcription factor	no		HMG_box_dom, SOX-12/11/4, HMG_box_dom_sf
CACNA1F	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, Ion_trans_dom
CCNB3	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
NDUFA12	Other/Unknown	no		NDUFA12
CYLD	Protease	yes		CAP-Gly_domain, Peptidase_C19_UCH, USP_CS
CCDC120	Other/Unknown	no		CUPID, CCDC120/INAVA
AKAP4	Other/Unknown	no		SPHK1-interactor_AKAP_110, AKAP_110_C, RII-bd_1
ERAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

7 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	2
male germ line stem cell (sensu Vertebrata) in testis	2
primordial germ cell in gonad	2
bronchial epithelial cell	1
epithelium of bronchus	1
cortical plate	1
embryo	1
ganglionic eminence	1
granulocyte	1
parotid gland	1
right hemisphere of cerebellum	1
left ventricle myocardium	1
myocardium	1
tibialis anterior	1
calcaneal tendon	1
lateral nuclear group of thalamus	1
lymph node	1
esophagus mucosa	1
lower esophagus mucosa	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC35A2	277	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, epithelium of bronchus
SOX11	93	broad	marker	ganglionic eminence, cortical plate, embryo
CACNA1F	143	tissue_specific	marker	parotid gland, granulocyte, right hemisphere of cerebellum
CCNB3	156	tissue_specific	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte
NDUFA12	255	ubiquitous	marker	left ventricle myocardium, tibialis anterior, myocardium
CYLD	294	ubiquitous	marker	lateral nuclear group of thalamus, calcaneal tendon, lymph node
CCDC120	162	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, skin of leg
AKAP4	62	tissue_specific	marker	sperm, male germ cell, left testis
ERAS	95		yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, hypothalamus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYLD	3,507
NDUFA12	3,068
CCNB3	2,576
SOX11	2,090
ERAS	2,024
SLC35A2	1,684
CACNA1F	1,616
CCDC120	1,218
AKAP4	1,149

Intra-cohort edges

A	B	Sources
AKAP4	CCNB3	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFA12	Q9UI09	7
CYLD	Q9NQC7	6
SOX11	P35716	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC35A2	P78381	80.59
ERAS	Q7Z444	79.71
CACNA1F	O60840	67.46
CCDC120	Q96HB5	56.34
AKAP4	Q5JQC9	53.52
CCNB3	Q8WWL7	42.25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 9 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective SLC35A2 causes congenital disorder of glycosylation 2M (CDG2M)	1	3806.7×	0.005	SLC35A2
Transport of nucleotide sugars	1	380.7×	0.024	SLC35A2
TNFR1-induced proapoptotic signaling	1	146.4×	0.028	CYLD
TNFR1-induced NF-kappa-B signaling pathway	1	112.0×	0.028	CYLD
Negative regulators of DDX58/IFIH1 signaling	1	108.8×	0.028	CYLD
NOD1/2 Signaling Pathway	1	105.7×	0.028	CYLD
Transport of vitamins, nucleosides, and related molecules	1	90.6×	0.028	SLC35A2
Regulation of TNFR1 signaling	1	74.6×	0.029	CYLD
SLC transporter disorders	1	68.0×	0.029	SLC35A2
Complex I biogenesis	1	55.2×	0.032	NDUFA12
Disorders of transmembrane transporters	1	46.4×	0.035	SLC35A2
Respiratory electron transport	1	31.7×	0.046	NDUFA12
Aerobic respiration and respiratory electron transport	1	29.5×	0.046	NDUFA12
SLC-mediated transmembrane transport	1	19.7×	0.064	SLC35A2
Ub-specific processing proteases	1	17.7×	0.067	CYLD
Transport of small molecules	1	8.4×	0.129	SLC35A2
Disease	1	4.4×	0.225	SLC35A2
Metabolism	1	3.9×	0.237	NDUFA12

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of interleukin-18-mediated signaling pathway	1	1872.4×	0.019	CYLD
negative regulation of transcription regulatory region DNA binding	1	1872.4×	0.019	SOX11
closure of optic fissure	1	936.2×	0.019	SOX11
UDP-galactose transmembrane transport	1	936.2×	0.019	SLC35A2
positive regulation of lens epithelial cell proliferation	1	936.2×	0.019	SOX11
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	624.1×	0.019	CYLD
ripoptosome assembly involved in necroptotic process	1	624.1×	0.019	CYLD
protein linear deubiquitination	1	624.1×	0.019	CYLD
negative regulation of lymphocyte proliferation	1	374.5×	0.023	SOX11
soft palate development	1	374.5×	0.023	SOX11
negative regulation of voltage-gated calcium channel activity	1	374.5×	0.023	CACNA1F
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	1	312.1×	0.023	CYLD
noradrenergic neuron differentiation	1	267.5×	0.023	SOX11
regulation of intrinsic apoptotic signaling pathway	1	267.5×	0.023	CYLD
galactose metabolic process	1	234.1×	0.023	SLC35A2
negative regulation of p38MAPK cascade	1	234.1×	0.023	CYLD
mitochondrial ATP synthesis coupled electron transport	1	208.1×	0.023	NDUFA12
regulation of necroptotic process	1	208.1×	0.023	CYLD
positive regulation of hormone secretion	1	187.2×	0.023	SOX11
hard palate development	1	187.2×	0.023	SOX11
negative regulation of glial cell proliferation	1	187.2×	0.023	SOX11
intracellular protein localization	2	23.3×	0.023	CCDC120, AKAP4
neuroepithelial cell differentiation	1	170.2×	0.023	SOX11
microtubule anchoring at centrosome	1	156.0×	0.023	CCDC120
positive regulation of protein localization	1	156.0×	0.023	CYLD
lens morphogenesis in camera-type eye	1	144.0×	0.023	SOX11
regulation of B cell differentiation	1	144.0×	0.023	CYLD
cornea development in camera-type eye	1	144.0×	0.023	SOX11
positive regulation of hippo signaling	1	117.0×	0.025	SOX11
lung morphogenesis	1	117.0×	0.025	SOX11

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 7

Druggability breadth: 5 of 9 evidence-associated genes (56%) 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
CACNA1F	BEPRIDIL
CCNB3	PALBOCICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1F	48	4
CCNB3	17	4
SLC35A2	0	0
SOX11	0	0
NDUFA12	0	0
CYLD	0	0
CCDC120	0	0
AKAP4	0	0
ERAS	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	CACNA1F
IMIPRAMINE	4	CACNA1F
HALOFANTRINE	4	CACNA1F
DROPERIDOL	4	CACNA1F
SAQUINAVIR	4	CACNA1F
DULOXETINE	4	CACNA1F
DIAZEPAM	4	CACNA1F
SERTINDOLE	4	CACNA1F
QUINIDINE	4	CACNA1F
LAMIVUDINE	4	CACNA1F
PIMOZIDE	4	CACNA1F
PHENYTOIN	4	CACNA1F
TERFENADINE	4	CACNA1F
CISAPRIDE	4	CACNA1F
SOLIFENACIN	4	CACNA1F
NIFEDIPINE	4	CACNA1F
DILTIAZEM	4	CACNA1F
NILOTINIB	4	CACNA1F
ASTEMIZOLE	4	CACNA1F
TERODILINE	4	CACNA1F
CLOZAPINE	4	CACNA1F
MIBEFRADIL	4	CACNA1F
DOFETILIDE	4	CACNA1F
THIORIDAZINE	4	CACNA1F
PAROXETINE	4	CACNA1F
DONEPEZIL	4	CACNA1F
IBUTILIDE	4	CACNA1F
SUNITINIB	4	CACNA1F
HALOPERIDOL	4	CACNA1F
DASATINIB	4	CACNA1F

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CACNA1F	221	Binding:135, Functional:79, Toxicity:5, ADMET:2
CCNB3	148	Binding:147, Functional:1
NDUFA12	4	Binding:4
CYLD	3	Binding:3
SLC35A2	1	ADMET:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CACNA1F	221
CCNB3	148

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
BEPRIDIL	4	CACNA1F
IMIPRAMINE	4	CACNA1F
HALOFANTRINE	4	CACNA1F
DROPERIDOL	4	CACNA1F
SAQUINAVIR	4	CACNA1F
DULOXETINE	4	CACNA1F
DIAZEPAM	4	CACNA1F
SERTINDOLE	4	CACNA1F
QUINIDINE	4	CACNA1F
LAMIVUDINE	4	CACNA1F
PIMOZIDE	4	CACNA1F
PHENYTOIN	4	CACNA1F
TERFENADINE	4	CACNA1F
CISAPRIDE	4	CACNA1F
SOLIFENACIN	4	CACNA1F
NIFEDIPINE	4	CACNA1F
DILTIAZEM	4	CACNA1F
NILOTINIB	4	CACNA1F
ASTEMIZOLE	4	CACNA1F
TERODILINE	4	CACNA1F
CLOZAPINE	4	CACNA1F
MIBEFRADIL	4	CACNA1F
DOFETILIDE	4	CACNA1F
THIORIDAZINE	4	CACNA1F
PAROXETINE	4	CACNA1F
DONEPEZIL	4	CACNA1F
IBUTILIDE	4	CACNA1F
SUNITINIB	4	CACNA1F
HALOPERIDOL	4	CACNA1F
DASATINIB	4	CACNA1F

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	CACNA1F, CCNB3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	CYLD
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	6	SLC35A2, SOX11, NDUFA12, CCDC120, AKAP4, ERAS

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC35A2	1	—
SOX11	0	—
NDUFA12	4	—
CYLD	3	—
CCDC120	0	—
AKAP4	0	—
ERAS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.