Imerslund-Grasbeck syndrome type 1

Summary

Imerslund-Grasbeck syndrome type 1 (MONDO:0100156) is a disease caused by variants in CUBN and AMN, with 3 cohort genes.

At a glance

• Causal genes: CUBN (GenCC Definitive), AMN (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 975

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Imerslund-Grasbeck syndrome type 1
Mondo ID	MONDO:0100156
OMIM	261100
NCIT	C131677
UMLS	C4016819
MedGen	865256
GARD	0026066
Is cancer (heuristic)	no

Also known as: enterocyte cobalamin malabsorption · enterocyte intrinsic factor receptor, defect of · Imerslund-Grasbeck syndrome 1 · Imerslund-Grasbeck syndrome type 1 · megaloblastic Anaemia type 1 · megaloblastic Anemia type 1 · megaloblastic anemia, 1 · megaloblastic anemia, Finnish type · MGA-1 · MGA1 · Mga1 · pernicious anemia, juvenile, due to selective intestinal malabsorption of vitamin b12, with proteinuria

Data availability: 975 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 › Imerslund-Grasbeck syndrome type 1

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, leukoencephalopathy with calcifications and cysts, 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 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

600 retrieved; paginated sample, class counts are floors:

347 uncertain significance, 77 conflicting classifications of pathogenicity, 62 benign, 33 likely pathogenic, 33 benign/likely benign, 27 likely benign, 12 pathogenic/likely pathogenic, 9 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1033271	NM_001081.4(CUBN):c.4165del (p.Tyr1389fs)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074937	NM_001081.4(CUBN):c.10462C>T (p.Arg3488Ter)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179172	NM_001081.4(CUBN):c.8755C>T (p.Arg2919Ter)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179174	NM_001081.4(CUBN):c.8463G>A (p.Trp2821Ter)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179177	NM_001081.4(CUBN):c.796G>T (p.Glu266Ter)	CUBN	Pathogenic	criteria provided, single submitter
1322175	NM_001081.4(CUBN):c.10612G>T (p.Glu3538Ter)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322176	NM_001081.4(CUBN):c.10233G>A (p.Trp3411Ter)	CUBN	Pathogenic	criteria provided, multiple submitters, no conflicts
1333207	NM_001081.4(CUBN):c.6821+3A>G	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1805548	NM_001081.4(CUBN):c.6894_6901dup (p.Leu2301Ter)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189227	NM_001081.4(CUBN):c.6928_6934del (p.Glu2310fs)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2147526	NM_001081.4(CUBN):c.8126_8127del (p.Ala2708_Tyr2709insTer)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2899860	NM_001081.4(CUBN):c.7471dup (p.Thr2491fs)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2960213	NM_001081.4(CUBN):c.6276C>A (p.Cys2092Ter)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
299439	NM_001081.4(CUBN):c.6359G>A (p.Trp2120Ter)	CUBN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30291	NM_001081.4(CUBN):c.3329+1G>T	CUBN	Pathogenic	no assertion criteria provided
3220910	NM_001081.4(CUBN):c.591C>G (p.Tyr197Ter)	CUBN	Pathogenic	criteria provided, single submitter
3235994	NM_001081.4(CUBN):c.4042G>T (p.Gly1348Ter)	CUBN	Pathogenic	criteria provided, single submitter
3235995	NM_001081.4(CUBN):c.6297_6298insT (p.Arg2100Ter)	CUBN	Pathogenic	criteria provided, single submitter
3336804	NM_001081.4(CUBN):c.2301G>C (p.Glu767Asp)	CUBN	Pathogenic	criteria provided, single submitter
3338368	NM_001081.4(CUBN):c.9286_9287del (p.Leu3096fs)	CUBN	Pathogenic	criteria provided, single submitter
3592109	NM_001081.4(CUBN):c.8707C>T (p.Gln2903Ter)	CUBN	Pathogenic	criteria provided, single submitter
1066455	NM_001081.4(CUBN):c.7001-2del	CUBN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1328629	NM_001081.4(CUBN):c.4350+2T>C	CUBN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1495871	NM_001081.4(CUBN):c.4856-1del	CUBN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1699902	NM_001081.4(CUBN):c.2792-1G>T	CUBN	Likely pathogenic	criteria provided, single submitter
2585161	NM_001081.4(CUBN):c.4351-1G>C	CUBN	Likely pathogenic	criteria provided, single submitter
3008677	NM_001081.4(CUBN):c.9237-1G>C	CUBN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3235177	NM_001081.4(CUBN):c.5927-1G>A	CUBN	Likely pathogenic	criteria provided, single submitter
3591639	NM_001081.4(CUBN):c.10246_10258del (p.Asp3416fs)	CUBN	Likely pathogenic	criteria provided, single submitter
3591768	NM_001081.4(CUBN):c.9664-2A>C	CUBN	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 19 · Orphanet: 6 · 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
CUBN	Definitive	Autosomal recessive	Imerslund-Grasbeck syndrome type 1	5
ABCD1	Strong	Autosomal recessive	Imerslund-Grasbeck syndrome type 1	11
AMN	Strong	Autosomal recessive	Imerslund-Grasbeck syndrome type 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AMN	Orphanet:35858	Imerslund-Gräsbeck syndrome
CUBN	Orphanet:35858	Imerslund-Gräsbeck syndrome
ABCD1	Orphanet:139396	X-linked cerebral adrenoleukodystrophy
ABCD1	Orphanet:139399	Adrenomyeloneuropathy
ABCD1	Orphanet:369942	CADDS
ABCD1	Orphanet:388	Hirschsprung disease

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AMN	HGNC:14604	ENSG00000166126	Q9BXJ7	Protein amnionless	gencc,clinvar
CUBN	HGNC:2548	ENSG00000107611	O60494	Cubilin	gencc,clinvar
ABCD1	HGNC:61	ENSG00000101986	P33897	ATP-binding cassette sub-family D member 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AMN	Protein amnionless	Membrane-bound component of the endocytic receptor formed by AMN and CUBN.
CUBN	Cubilin	Endocytic receptor which plays a role in lipoprotein, vitamin and iron metabolism by facilitating their uptake.
ABCD1	ATP-binding cassette sub-family D member 1	ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Transporter	1	25.9×	0.076
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AMN	Other/Unknown	no		AMN
CUBN	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom
ABCD1	Transporter	yes	7.6.2.4	ABC_transporter-like_ATP-bd, AAA+_ATPase, FA_transporter

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
duodenum	1
jejunal mucosa	1
mucosa of transverse colon	1
adult organism	1
kidney epithelium	1
nephron tubule	1
ileal mucosa	1
left adrenal gland	1
left adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AMN	223	broad	marker	mucosa of transverse colon, jejunal mucosa, duodenum
CUBN	188	broad	marker	adult organism, nephron tubule, kidney epithelium
ABCD1	201	ubiquitous	marker	ileal mucosa, left adrenal gland cortex, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CUBN	1,193
ABCD1	1,181
AMN	414

Intra-cohort edges

A	B	Sources
AMN	CUBN	intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCD1	P33897	14
CUBN	O60494	2
AMN	Q9BXJ7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 30. Enrichment computed across 3 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 AMN causes MGA1	2	2537.8×	2e-06	AMN, CUBN
Defective CUBN causes MGA1	2	2537.8×	2e-06	AMN, CUBN
HDL clearance	2	1522.7×	5e-06	AMN, CUBN
Uptake of dietary cobalamins into enterocytes	2	761.3×	2e-05	AMN, CUBN
Defective ABCD1 causes ALD	1	1903.3×	0.003	ABCD1
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	1	634.4×	0.008	ABCD1
Linoleic acid (LA) metabolism	1	380.7×	0.009	ABCD1
Vitamin D (calciferol) metabolism	1	292.8×	0.009	CUBN
Beta-oxidation of very long chain fatty acids	1	292.8×	0.009	ABCD1
Defects in cobalamin (B12) metabolism	1	271.9×	0.009	AMN
alpha-linolenic acid (ALA) metabolism	1	237.9×	0.009	ABCD1
Peroxisomal lipid metabolism	1	223.9×	0.009	ABCD1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	211.5×	0.009	AMN
ABC transporters in lipid homeostasis	1	200.3×	0.009	ABCD1
Defects in vitamin and cofactor metabolism	1	200.3×	0.009	AMN
Transport of small molecules	2	16.8×	0.009	AMN, ABCD1
Class I peroxisomal membrane protein import	1	173.0×	0.010	ABCD1
Plasma lipoprotein clearance	1	158.6×	0.010	AMN
ABC transporter disorders	1	146.4×	0.011	ABCD1
Plasma lipoprotein assembly, remodeling, and clearance	1	76.1×	0.020	AMN
Protein localization	1	63.4×	0.022	ABCD1
Metabolism of water-soluble vitamins and cofactors	1	60.4×	0.022	AMN
Disease	2	8.7×	0.022	AMN, ABCD1
Disorders of transmembrane transporters	1	46.4×	0.026	ABCD1
Metabolism	2	7.7×	0.026	AMN, ABCD1
Fatty acid metabolism	1	43.8×	0.026	ABCD1
ABC-family protein mediated transport	1	40.5×	0.027	ABCD1
Metabolism of vitamins and cofactors	1	38.8×	0.027	AMN
Diseases of metabolism	1	26.8×	0.038	AMN
Metabolism of lipids	1	10.5×	0.092	ABCD1

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
cobalamin transport	2	1248.3×	2e-05	AMN, CUBN
cobalamin metabolic process	2	1021.3×	2e-05	AMN, CUBN
receptor-mediated endocytosis	2	147.8×	7e-04	AMN, CUBN
peroxisomal membrane transport	1	2808.7×	0.003	ABCD1
very long-chain fatty-acyl-CoA catabolic process	1	2808.7×	0.003	ABCD1
renal protein absorption	1	1872.4×	0.003	AMN
positive regulation of unsaturated fatty acid biosynthetic process	1	1872.4×	0.003	ABCD1
sterol homeostasis	1	1404.3×	0.003	ABCD1
long-chain fatty acid import into peroxisome	1	1123.5×	0.003	ABCD1
regulation of fatty acid beta-oxidation	1	936.2×	0.003	ABCD1
long-chain fatty acid catabolic process	1	936.2×	0.003	ABCD1
myelin maintenance	1	936.2×	0.003	ABCD1
regulation of mitochondrial depolarization	1	936.2×	0.003	ABCD1
fatty acid elongation	1	802.5×	0.003	ABCD1
very long-chain fatty acid catabolic process	1	802.5×	0.003	ABCD1
positive regulation of fatty acid beta-oxidation	1	510.7×	0.004	ABCD1
fatty acid derivative biosynthetic process	1	510.7×	0.004	ABCD1
regulation of cellular response to oxidative stress	1	432.1×	0.005	ABCD1
regulation of oxidative phosphorylation	1	401.2×	0.005	ABCD1
neuron projection maintenance	1	374.5×	0.005	ABCD1
lipoprotein transport	1	330.4×	0.005	CUBN
negative regulation of reactive oxygen species biosynthetic process	1	330.4×	0.005	ABCD1
fatty acid homeostasis	1	312.1×	0.005	ABCD1
alpha-linolenic acid metabolic process	1	295.6×	0.005	ABCD1
peroxisome organization	1	267.5×	0.006	ABCD1
very long-chain fatty acid metabolic process	1	255.3×	0.006	ABCD1
linoleic acid metabolic process	1	234.1×	0.006	ABCD1
unsaturated fatty acid biosynthetic process	1	216.1×	0.006	ABCD1
tissue homeostasis	1	187.2×	0.007	CUBN
Golgi to plasma membrane protein transport	1	175.5×	0.007	AMN

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
AMN	0	0
CUBN	0	0
ABCD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCD1	7.6.2.4	ABC-type fatty-acyl-CoA transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	ABCD1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	AMN, CUBN

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AMN	0	—
CUBN	0	—
ABCD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.