ALG12-congenital disorder of glycosylation

Summary

ALG12-congenital disorder of glycosylation (MONDO:0011783) is a disease caused by ALG12 (GenCC Definitive), with 5 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ALG12 (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 520
• Phenotypes (HPO): 93

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		11	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0012379	Abnormal enzyme/coenzyme activity	Obligate (100%)
HP:0000119	Abnormality of the genitourinary system	Very frequent (80-99%)
HP:0003256	Abnormality of the coagulation cascade	Very frequent (80-99%)
HP:0000253	Progressive microcephaly	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0000759	Abnormal peripheral nervous system morphology	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001929	Reduced factor XI activity	Frequent (30-79%)
HP:0002011	Morphological central nervous system abnormality	Frequent (30-79%)
HP:0002194	Delayed gross motor development	Frequent (30-79%)
HP:0002205	Recurrent respiratory infections	Frequent (30-79%)
HP:0002257	Chronic rhinitis	Frequent (30-79%)
HP:0003645	Prolonged partial thromboplastin time	Frequent (30-79%)
HP:0004855	Reduced protein S activity	Frequent (30-79%)
HP:0005543	Reduced protein C activity	Frequent (30-79%)
HP:0006532	Recurrent pneumonia	Frequent (30-79%)
HP:0008151	Prolonged prothrombin time	Frequent (30-79%)
HP:0010976	Decreased total B cell count	Frequent (30-79%)
HP:0011968	Feeding difficulties	Frequent (30-79%)
HP:0040246	Reduced antithrombin antigen	Frequent (30-79%)
HP:0100776	Recurrent pharyngitis	Frequent (30-79%)
HP:0410018	Recurrent ear infections	Frequent (30-79%)
HP:0410242	Abnormal IgG level	Frequent (30-79%)
HP:0001622	Premature birth	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0001792	Small nail	Occasional (5-29%)
HP:0001852	Sandal gap	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0001988	Recurrent hypoglycemia	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002020	Gastroesophageal reflux	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002162	Low posterior hairline	Occasional (5-29%)
HP:0002389	Cavum septum pellucidum	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0003026	Short long bone	Occasional (5-29%)
HP:0003049	Ulnar deviation of the wrist	Occasional (5-29%)
HP:0003073	Hypoalbuminemia	Occasional (5-29%)
HP:0003146	Hypocholesterolemia	Occasional (5-29%)
HP:0004209	Clinodactyly of the 5th finger	Occasional (5-29%)
HP:0009623	Proximal placement of thumb	Occasional (5-29%)
HP:0010557	Overlapping fingers	Occasional (5-29%)
HP:0011327	Posterior plagiocephaly	Occasional (5-29%)
HP:0011344	Severe global developmental delay	Occasional (5-29%)
HP:0011471	Gastrostomy tube feeding in infancy	Occasional (5-29%)
HP:0011800	Midface retrusion	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ALG12-congenital disorder of glycosylation
Mondo ID	MONDO:0011783
MeSH	C535745
OMIM	607143
Orphanet	79324
DOID	DOID:0080559
NCIT	C126873
SNOMED CT	711155008
UMLS	C2931001
MedGen	443954
GARD	0009833
Is cancer (heuristic)	no

Also known as: ALG12-CDG · ALG12-CDG (CDG-Ig) · ALG12-congenital disorder of glycosylation · carbohydrate deficient glycoprotein syndrome type Ig · CDG 1G · CDG syndrome type Ig · CDG-Ig · CDG1G · CDGIg · congenital disorder of glycosylation type 1g · congenital disorder of glycosylation type Ig · congenital disorder of glycosylation, type Ig · mannosyltransferase 8 deficiency

Data availability: 520 ClinVar variants · 5 GenCC gene-disease records · 2 cell lines.

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 I › ALG12-congenital disorder of glycosylation

Related subtypes (27): PMM2-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 36, SSR4-congenital disorder of glycosylation, ALG3-congenital disorder of glycosylation, MPI-congenital disorder of glycosylation, ALG6-congenital disorder of glycosylation 1C, ALG2-congenital disorder of glycosylation, DPAGT1-congenital disorder of glycosylation, ALG8-congenital disorder of glycosylation, ALG1-congenital disorder of glycosylation, ALG9-congenital disorder of glycosylation, congenital disorder of glycosylation type 1E, MPDU1-congenital disorder of glycosylation, DK1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, SRD5A3-congenital disorder of glycosylation, DPM3-congenital disorder of glycosylation, ALG11-congenital disorder of glycosylation, DDOST-congenital disorder of glycosylation, PGM1-congenital disorder of glycosylation, congenital muscular dystrophy with intellectual disability and severe epilepsy, STT3A-congenital disorder of glycosylation, STT3B-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 50, congenital disorder of glycosylation, type IAA, congenital disorder of glycosylation, type ICC, SSR3-CDG

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

520 retrieved; paginated sample, class counts are floors:

225 likely benign, 193 uncertain significance, 32 conflicting classifications of pathogenicity, 24 pathogenic, 19 benign, 13 likely pathogenic, 7 pathogenic/likely pathogenic, 7 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4724	NM_019109.5(ALG1):c.773C>T (p.Ser258Leu)	ALG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069034	NM_024105.4(ALG12):c.1156dup (p.Gln386fs)	ALG12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1383200	NM_024105.4(ALG12):c.522G>A (p.Trp174Ter)	ALG12	Pathogenic	criteria provided, single submitter
1440773	NM_024105.4(ALG12):c.789C>A (p.Tyr263Ter)	ALG12	Pathogenic	criteria provided, single submitter
1448154	NM_024105.4(ALG12):c.502G>T (p.Glu168Ter)	ALG12	Pathogenic	criteria provided, single submitter
1456464	NM_024105.4(ALG12):c.688dup (p.Tyr230fs)	ALG12	Pathogenic	criteria provided, single submitter
2073899	NM_024105.4(ALG12):c.336G>A (p.Trp112Ter)	ALG12	Pathogenic	criteria provided, single submitter
2090231	NM_024105.4(ALG12):c.1129C>T (p.Gln377Ter)	ALG12	Pathogenic	criteria provided, single submitter
2103386	NM_024105.4(ALG12):c.424_428delinsCAGTTCCAC (p.Phe142fs)	ALG12	Pathogenic	criteria provided, single submitter
2138458	NM_024105.4(ALG12):c.30del (p.Leu12fs)	ALG12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2426800	NC_000022.10:g.(?50297486)(50307413_?)del	ALG12	Pathogenic	criteria provided, single submitter
242854	NM_024105.4(ALG12):c.1001del (p.Asn334fs)	ALG12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
242855	NM_024105.4(ALG12):c.117del (p.Gln40fs)	ALG12	Pathogenic	criteria provided, multiple submitters, no conflicts
2626751	NM_024105.4(ALG12):c.768+1dup	ALG12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2697267	NM_024105.4(ALG12):c.698_699del (p.Arg233fs)	ALG12	Pathogenic	criteria provided, single submitter
2734803	NM_024105.4(ALG12):c.731G>A (p.Trp244Ter)	ALG12	Pathogenic	criteria provided, single submitter
2824299	NM_024105.4(ALG12):c.160C>T (p.Gln54Ter)	ALG12	Pathogenic	criteria provided, single submitter
2839616	NM_024105.4(ALG12):c.21_33dup (p.Leu12fs)	ALG12	Pathogenic	criteria provided, single submitter
3358165	NM_024105.4(ALG12):c.604C>T (p.Arg202Ter)	ALG12	Pathogenic	criteria provided, single submitter
3434	NM_024105.4(ALG12):c.200C>T (p.Thr67Met)	ALG12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3435	NM_024105.4(ALG12):c.437G>A (p.Arg146Gln)	ALG12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3437	NM_024105.4(ALG12):c.473T>C (p.Leu158Pro)	ALG12	Pathogenic	no assertion criteria provided
3438	NM_024105.4(ALG12):c.1242C>G (p.Tyr414Ter)	ALG12	Pathogenic	no assertion criteria provided
3617623	NM_024105.4(ALG12):c.755del (p.Ser252fs)	ALG12	Pathogenic	criteria provided, single submitter
3688618	NM_024105.4(ALG12):c.1015_1016del (p.Trp339fs)	ALG12	Pathogenic	criteria provided, single submitter
4697444	NM_024105.4(ALG12):c.861del (p.Thr288fs)	ALG12	Pathogenic	criteria provided, single submitter
4767896	NM_024105.4(ALG12):c.904_908del (p.Tyr302fs)	ALG12	Pathogenic	criteria provided, single submitter
560937	NM_024105.4(ALG12):c.930_931del (p.Arg311fs)	ALG12	Pathogenic	criteria provided, multiple submitters, no conflicts
987881	NM_024105.4(ALG12):c.165C>A (p.Tyr55Ter)	ALG12	Pathogenic	criteria provided, single submitter
1031734	NM_007347.5(AP4E1):c.3313C>T (p.Arg1105Ter)	AP4E1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
ALG12	Definitive	Autosomal recessive	ALG12-congenital disorder of glycosylation	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ALG12	Orphanet:79324	ALG12-CDG
ALG1	Orphanet:79327	ALG1-CDG
AP4E1	Orphanet:280763	Severe intellectual disability and progressive spastic paraplegia

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ALG12	HGNC:19358	ENSG00000182858	Q9BV10	Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase	gencc,clinvar
BRD1	HGNC:1102	ENSG00000100425	O95696	Bromodomain-containing protein 1	clinvar
ALG1	HGNC:18294	ENSG00000033011	Q9BT22	Chitobiosyldiphosphodolichol beta-mannosyltransferase	clinvar
AP4E1	HGNC:573	ENSG00000081014	Q9UPM8	AP-4 complex subunit epsilon-1	clinvar
PLXNB2	HGNC:9104	ENSG00000196576	O15031	Plexin-B2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ALG12	Dol-P-Man:Man(7)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase	Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
BRD1	Bromodomain-containing protein 1	Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, that acts as a regulator of hematopoiesis.
ALG1	Chitobiosyldiphosphodolichol beta-mannosyltransferase	Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
AP4E1	AP-4 complex subunit epsilon-1	Component of the adaptor protein complex 4 (AP-4).
PLXNB2	Plexin-B2	Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.6

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)	2	4.8×	0.235
Antibody/Immunoglobulin	1	5.8×	0.320
Transcription factor	1	1.6×	0.634
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ALG12	Enzyme (other)	yes	2.4.1.260	GPI_mannosylTrfase
BRD1	Transcription factor	no		PWWP_dom, Bromodomain, Znf_PHD
ALG1	Enzyme (other)	yes	2.4.1.142	Glyco_trans_1, ALG1-like
AP4E1	Other/Unknown	no		Clathrin/coatomer_adapt-like_N, ARM-like, ARM-type_fold
PLXNB2	Antibody/Immunoglobulin	yes		Semap_dom, Plexin_repeat, IPT_dom

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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
buccal mucosa cell	2
left lobe of thyroid gland	1
right lobe of thyroid gland	1
oocyte	1
paraflocculus	1
secondary oocyte	1
body of pancreas	1
esophagus squamous epithelium	1
gingival epithelium	1
lower esophagus mucosa	1
metanephros cortex	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ALG12	217	ubiquitous	marker	right lobe of thyroid gland, stromal cell of endometrium, left lobe of thyroid gland
BRD1	289	ubiquitous	marker	oocyte, secondary oocyte, paraflocculus
ALG1	185	ubiquitous	marker	stromal cell of endometrium, buccal mucosa cell, body of pancreas
AP4E1	262	ubiquitous	yes	gingival epithelium, esophagus squamous epithelium, buccal mucosa cell
PLXNB2	276	ubiquitous	marker	right uterine tube, metanephros cortex, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRD1	2,359
ALG1	2,187
AP4E1	2,108
PLXNB2	1,606
ALG12	1,385

Intra-cohort edges

A	B	Sources
ALG1	ALG12	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRD1	O95696	318
AP4E1	Q9UPM8	4
PLXNB2	O15031	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ALG12	Q9BV10	93.26
ALG1	Q9BT22	93.24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 5 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
Diseases associated with N-glycosylation of proteins	2	317.2×	3e-04	ALG12, ALG1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	2	103.8×	0.002	ALG12, ALG1
Defective ALG1 causes CDG-1k	1	2855.0×	0.002	ALG1
Defective ALG12 causes CDG-1g	1	2855.0×	0.002	ALG12
Diseases of glycosylation	2	65.6×	0.002	ALG12, ALG1
Diseases of metabolism	2	40.2×	0.004	ALG12, ALG1
Asparagine N-linked glycosylation	2	30.1×	0.006	ALG12, ALG1
Regulation of TP53 Activity through Acetylation	1	114.2×	0.026	BRD1
Lysosome Vesicle Biogenesis	1	81.6×	0.033	AP4E1
trans-Golgi Network Vesicle Budding	1	63.4×	0.034	AP4E1
Post-translational protein modification	2	9.6×	0.034	ALG12, ALG1
Golgi Associated Vesicle Biogenesis	1	50.1×	0.040	AP4E1
Regulation of TP53 Activity	1	33.2×	0.054	BRD1
Disease	2	6.5×	0.054	ALG12, ALG1
Metabolism of proteins	2	6.2×	0.056	ALG12, ALG1
Chromatin organization	1	20.4×	0.070	BRD1
HATs acetylate histones	1	19.8×	0.070	BRD1
Chromatin modifying enzymes	1	18.1×	0.072	BRD1
Transcriptional Regulation by TP53	1	15.5×	0.079	BRD1
Membrane Trafficking	1	9.3×	0.124	AP4E1
Vesicle-mediated transport	1	8.7×	0.126	AP4E1
RNA Polymerase II Transcription	1	5.6×	0.181	BRD1
Gene expression (Transcription)	1	4.5×	0.215	BRD1
Generic Transcription Pathway	1	3.8×	0.240	BRD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
dolichol-linked oligosaccharide biosynthetic process	2	337.0×	4e-04	ALG12, ALG1
protein N-linked glycosylation	2	105.3×	0.002	ALG12, ALG1
regulation of developmental process	1	481.5×	0.023	BRD1
regulation of hemopoiesis	1	306.4×	0.024	BRD1
excitatory synapse assembly	1	259.3×	0.024	PLXNB2
regulation of protein phosphorylation	1	224.7×	0.024	PLXNB2
erythrocyte maturation	1	168.5×	0.025	BRD1
response to immobilization stress	1	146.5×	0.025	BRD1
response to electrical stimulus	1	129.6×	0.025	BRD1
regulation of neuron migration	1	124.8×	0.025	PLXNB2
positive regulation of axonogenesis	1	116.2×	0.025	PLXNB2
regulation of GTPase activity	1	102.1×	0.025	PLXNB2
positive regulation of erythrocyte differentiation	1	102.1×	0.025	BRD1
semaphorin-plexin signaling pathway	1	80.2×	0.026	PLXNB2
negative regulation of cell adhesion	1	76.6×	0.026	PLXNB2
protein targeting	1	73.3×	0.026	AP4E1
neuroblast proliferation	1	73.3×	0.026	PLXNB2
synapse assembly	1	46.2×	0.037	PLXNB2
positive regulation of translation	1	45.5×	0.037	PLXNB2
receptor-mediated endocytosis	1	44.4×	0.037	PLXNB2
neural tube closure	1	37.5×	0.042	PLXNB2
regulation of cell migration	1	31.5×	0.047	PLXNB2
homophilic cell-cell adhesion	1	28.1×	0.049	PLXNB2
positive regulation of neuron projection development	1	27.4×	0.049	PLXNB2
regulation of cell shape	1	24.6×	0.053	PLXNB2
intracellular protein localization	1	20.9×	0.058	AP4E1
protein folding	1	20.7×	0.058	ALG12
vesicle-mediated transport	1	19.3×	0.060	AP4E1
brain development	1	15.9×	0.070	PLXNB2
chromatin remodeling	1	14.6×	0.073	BRD1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALG12	0	0
BRD1	0	0
ALG1	0	0
AP4E1	0	0
PLXNB2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
BRD1	121	Binding:118, Functional:3
ALG1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALG12	2.4.1.260	dolichyl-P-Man:Man7GlcNAc2-PP-dolichol alpha-1,6-mannosyltransferase
ALG1	2.4.1.142	chitobiosyldiphosphodolichol beta-mannosyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BRD1	121

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	PLXNB2
D	Druggable family + AlphaFold only, no drug	2	ALG12, ALG1
E	Difficult family or no structure, no drug	2	BRD1, AP4E1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRD1	121	—
ALG12	0	—
ALG1	1	—
AP4E1	0	—
PLXNB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.