Donnai-Barrow syndrome

Summary

Donnai-Barrow syndrome (MONDO:0009104) is a disease caused by LRP2 (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: LRP2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1,246
• Phenotypes (HPO): 28
• Clinical trials: 1

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)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0000093	Proteinuria	Very frequent (80-99%)
HP:0000260	Wide anterior fontanel	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000349	Widow’s peak	Very frequent (80-99%)
HP:0000358	Posteriorly rotated ears	Very frequent (80-99%)
HP:0000407	Sensorineural hearing impairment	Very frequent (80-99%)
HP:0000494	Downslanted palpebral fissures	Very frequent (80-99%)
HP:0000545	Myopia	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0005280	Depressed nasal bridge	Very frequent (80-99%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Very frequent (80-99%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000337	Broad forehead	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0000529	Progressive visual loss	Frequent (30-79%)
HP:0000541	Retinal detachment	Frequent (30-79%)
HP:0000776	Congenital diaphragmatic hernia	Frequent (30-79%)
HP:0001537	Umbilical hernia	Frequent (30-79%)
HP:0001539	Omphalocele	Frequent (30-79%)
HP:0000130	Abnormality of the uterus	Occasional (5-29%)
HP:0000556	Retinal dystrophy	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000813	Bicornuate uterus	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0002566	Intestinal malrotation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Donnai-Barrow syndrome
Mondo ID	MONDO:0009104
MeSH	C536390
OMIM	222448
Orphanet	2143
DOID	DOID:0090144
SNOMED CT	702418009
UMLS	C1857277
MedGen	347406
GARD	0001899
Is cancer (heuristic)	no

Also known as: DBS/FOAR syndrome · diaphragmatic hernia exomphalos absent corpus callosum hypertelorism myopia sensorineural deafness and proteinuria · diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia, sensorineural deafness, and proteinuria · diaphragmatic hernia-exomphalos-hypertelorism syndrome · diaphragmatic hernia-hypertelorism-myopia-deafness syndrome · Donnai-Barrow syndrome · facio-oculo-acoustico-renal syndrome · faciooculoacousticorenal syndrome · FOAR syndrome · Holmes-Schepens syndrome · syndrome of ocular and facial anomalies, telecanthus and deafness

Data availability: 1,246 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 › Donnai-Barrow syndrome

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, 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 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

600 retrieved; paginated sample, class counts are floors:

345 uncertain significance, 79 conflicting classifications of pathogenicity, 75 likely benign, 45 benign, 32 benign/likely benign, 13 likely pathogenic, 6 pathogenic/likely pathogenic, 3 pathogenic, 2 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1324679	NM_004525.3(LRP2):c.6673C>T (p.Arg2225Ter)	LRP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1375164	NM_004525.3(LRP2):c.11323C>T (p.Arg3775Ter)	LRP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458573	NM_004525.3(LRP2):c.10660C>T (p.Arg3554Ter)	LRP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526144	NM_004525.3(LRP2):c.8244T>A (p.Cys2748Ter)	LRP2	Pathogenic	criteria provided, single submitter
211391	NM_004525.3(LRP2):c.13139del (p.Pro4380fs)	LRP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21418	NM_004525.3(LRP2):c.11469_11472del (p.Cys3823fs)	LRP2	Pathogenic	criteria provided, single submitter
21419	NM_004525.3(LRP2):c.13139dup (p.Cys4381fs)	LRP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734334	NM_004525.3(LRP2):c.9550C>T (p.Arg3184Ter)	LRP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2860294	NM_004525.3(LRP2):c.12136C>T (p.Arg4046Ter)	LRP2	Pathogenic	criteria provided, multiple submitters, no conflicts
1179162	GRCh37/hg19 2q31.1(chr2:170134234-170137049)	LRP2	Likely pathogenic	no assertion criteria provided
1184542	NM_004525.3(LRP2):c.8095C>T (p.Arg2699Ter)	LRP2	Likely pathogenic	no assertion criteria provided
1184543	NM_004525.3(LRP2):c.7840A>T (p.Arg2614Ter)	LRP2	Likely pathogenic	no assertion criteria provided
1344817	NM_004525.3(LRP2):c.857G>T (p.Cys286Phe)	LRP2	Likely pathogenic	no assertion criteria provided
1344818	NM_004525.3(LRP2):c.12623C>A (p.Pro4208His)	LRP2	Likely pathogenic	no assertion criteria provided
1344819	NM_004525.3(LRP2):c.9575G>A (p.Arg3192Gln)	LRP2	Likely pathogenic	no assertion criteria provided
1677113	NC_000002.11:g.(170034537_170037957)_(170072941_170076963)del	LRP2	Likely pathogenic	criteria provided, single submitter
1722403	NM_004525.3(LRP2):c.2006del (p.Gly669fs)	LRP2	Likely pathogenic	criteria provided, single submitter
225405	NM_004525.3(LRP2):c.188-2A>G	LRP2	Likely pathogenic	criteria provided, single submitter
2441245	NM_004525.3(LRP2):c.11868del (p.Trp3956fs)	LRP2	Likely pathogenic	criteria provided, single submitter
2701133	NM_004525.3(LRP2):c.427+1del	LRP2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2838129	NM_004525.3(LRP2):c.12019+1G>A	LRP2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2974494	NM_004525.3(LRP2):c.13620+1G>T	LRP2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
225404	NM_018368.4(LMBRD1):c.981-10dup	LMBRD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002694	NM_004525.3(LRP2):c.10948C>A (p.Gln3650Lys)	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007775	NM_004525.3(LRP2):c.5867T>G (p.Leu1956Arg)	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1019130	NM_004525.3(LRP2):c.3013A>G (p.Arg1005Gly)	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029856	NM_004525.3(LRP2):c.428-4A>G	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1046181	NM_004525.3(LRP2):c.8352G>A (p.Thr2784=)	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1058836	NM_004525.3(LRP2):c.7247A>G (p.Asn2416Ser)	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1060104	NM_004525.3(LRP2):c.11504G>A (p.Arg3835His)	LRP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
LRP2	Definitive	Autosomal recessive	Donnai-Barrow syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LRP2	Orphanet:2143	Donnai-Barrow syndrome
LMBRD1	Orphanet:79284	Methylmalonic acidemia with homocystinuria type cblF

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRP2	HGNC:6694	ENSG00000081479	P98164	Low-density lipoprotein receptor-related protein 2	gencc,clinvar
LMBRD1	HGNC:23038	ENSG00000168216	Q9NUN5	Lysosomal cobalamin transport escort protein LMBD1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LRP2	Low-density lipoprotein receptor-related protein 2	Multiligand endocytic receptor.
LMBRD1	Lysosomal cobalamin transport escort protein LMBD1	Lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRP2	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
LMBRD1	Other/Unknown	no		LMBR1-like_membr_prot, LMBD1_LysCbl_Transport

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adult mammalian kidney	1
adult organism	1
corpus callosum	1
oocyte	1
pigmented layer of retina	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRP2	169	broad	marker	adult organism, adult mammalian kidney, corpus callosum
LMBRD1	288	ubiquitous	marker	secondary oocyte, oocyte, pigmented layer of retina

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRP2	2,501
LMBRD1	609

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRP2	P98164	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LMBRD1	Q9NUN5	84.17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transport of RCbl within the body	2	1427.5×	1e-05	LRP2, LMBRD1
Cobalamin (Cbl, vitamin B12) transport and metabolism	2	634.4×	3e-05	LRP2, LMBRD1
Metabolism of water-soluble vitamins and cofactors	2	181.3×	2e-04	LRP2, LMBRD1
Metabolism of vitamins and cofactors	2	116.5×	4e-04	LRP2, LMBRD1
Defective ABCD4 causes MAHCJ	1	2855.0×	0.002	LMBRD1
Uptake of dietary cobalamins into enterocytes	1	571.0×	0.007	LMBRD1
Vitamin D (calciferol) metabolism	1	439.2×	0.007	LRP2
Defects in cobalamin (B12) metabolism	1	407.9×	0.007	LMBRD1
Defects in vitamin and cofactor metabolism	1	300.5×	0.009	LMBRD1
ABC transporter disorders	1	219.6×	0.011	LMBRD1
Metabolism of fat-soluble vitamins	1	190.3×	0.011	LRP2
Visual phototransduction	1	129.8×	0.014	LRP2
Retinoid metabolism and transport	1	124.1×	0.014	LRP2
Metabolism	2	11.6×	0.014	LRP2, LMBRD1
Disorders of transmembrane transporters	1	69.6×	0.022	LMBRD1
Metabolism of steroids	1	68.8×	0.022	LRP2
Cargo recognition for clathrin-mediated endocytosis	1	52.4×	0.027	LRP2
Sensory Perception	1	47.6×	0.028	LRP2
Clathrin-mediated endocytosis	1	42.6×	0.029	LRP2
Diseases of metabolism	1	40.2×	0.030	LMBRD1
Membrane Trafficking	1	18.5×	0.061	LRP2
Vesicle-mediated transport	1	17.4×	0.062	LRP2
Metabolism of lipids	1	15.8×	0.065	LRP2
Disease	1	6.5×	0.147	LMBRD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
diol metabolic process	1	8426.0×	0.003	LRP2
positive regulation of oligodendrocyte progenitor proliferation	1	4213.0×	0.003	LRP2
insulin receptor internalization	1	2808.7×	0.003	LMBRD1
folate import across plasma membrane	1	2106.5×	0.003	LRP2
positive regulation of lysosomal protein catabolic process	1	1685.2×	0.003	LRP2
pulmonary artery morphogenesis	1	1404.3×	0.003	LRP2
ventricular compact myocardium morphogenesis	1	1203.7×	0.003	LRP2
response to leptin	1	1203.7×	0.003	LRP2
cobalamin transport	1	936.2×	0.003	LRP2
metal ion transport	1	936.2×	0.003	LRP2
coronary artery morphogenesis	1	936.2×	0.003	LRP2
neuron projection arborization	1	936.2×	0.003	LRP2
transcytosis	1	842.6×	0.003	LRP2
secondary heart field specification	1	766.0×	0.003	LRP2
vitamin D metabolic process	1	766.0×	0.003	LRP2
vagina development	1	766.0×	0.003	LRP2
protein localization to lysosome	1	526.6×	0.005	LMBRD1
amyloid-beta clearance	1	468.1×	0.005	LRP2
cranial skeletal system development	1	468.1×	0.005	LRP2
gastrulation	1	351.1×	0.006	LMBRD1
outflow tract septum morphogenesis	1	324.1×	0.006	LRP2
positive regulation of neurogenesis	1	290.6×	0.006	LRP2
clathrin-dependent endocytosis	1	290.6×	0.006	LMBRD1
aorta development	1	280.9×	0.006	LRP2
retinoid metabolic process	1	247.8×	0.007	LRP2
ventricular septum development	1	247.8×	0.007	LRP2
forebrain development	1	175.5×	0.009	LRP2
cellular response to growth factor stimulus	1	159.0×	0.009	LRP2
negative regulation of BMP signaling pathway	1	145.3×	0.010	LRP2
receptor-mediated endocytosis	1	110.9×	0.013	LRP2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LRP2	0	0
LMBRD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
LRP2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	LRP2, LMBRD1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LRP2	1	—
LMBRD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01509287	Not specified	COMPLETED	Metabolic Screening in Patients With Donnai-Barrow Syndrome