brain small vessel disease 2A, autosomal dominant

Summary

brain small vessel disease 2A, autosomal dominant (MONDO:0013773) is a disease caused by COL4A2 (GenCC Strong), with 5 cohort genes. The dominant Reactome pathway is Anchoring fibril formation (3 cohort genes).

At a glance

• Causal gene: COL4A2 (GenCC Strong)
• Cohort genes: 5
• ClinVar variants: 306

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain small vessel disease 2A, autosomal dominant
Mondo ID	MONDO:0013773
OMIM	614483
DOID	DOID:0112314
UMLS	C3280970
MedGen	482600
GARD	0015808
Is cancer (heuristic)	no

Also known as: brain small vessel disease 2 · COL4A2 porencephaly · POREN2 · porencephaly 2 · porencephaly type 2

Data availability: 306 ClinVar variants · 3 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 dominant disease › brain small vessel disease 2A, autosomal dominant

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

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

306 retrieved; paginated sample, class counts are floors:

101 uncertain significance, 66 benign, 51 conflicting classifications of pathogenicity, 48 benign/likely benign, 20 likely pathogenic, 12 likely benign, 7 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1299561	NM_001846.4(COL4A2):c.1011+1G>A	COL4A2	Pathogenic	criteria provided, single submitter
2121413	NM_001846.4(COL4A2):c.361-1G>A	COL4A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29627	NM_001846.4(COL4A2):c.3455G>A (p.Gly1152Asp)	COL4A2	Pathogenic	no assertion criteria provided
29628	NM_001846.4(COL4A2):c.3110G>A (p.Gly1037Glu)	COL4A2	Pathogenic	no assertion criteria provided
3339986	NC_000013.10:g.(111138184_111141791)_(111156612_111158761)del	COL4A2	Pathogenic	criteria provided, single submitter
3896611	NM_001846.4(COL4A2):c.2019_2022del (p.Gln674fs)	COL4A2	Pathogenic	criteria provided, single submitter
560985	NM_001846.4(COL4A2):c.316-1G>C	COL4A2	Pathogenic	criteria provided, single submitter
689504	NM_001846.4(COL4A2):c.4129G>A (p.Gly1377Arg)	COL4A2	Pathogenic	no assertion criteria provided
1677010	NM_001846.4(COL4A2):c.4557C>A (p.Tyr1519Ter)	COL4A2	Likely pathogenic	criteria provided, single submitter
1679295	NM_001846.4(COL4A2):c.668G>A (p.Gly223Glu)	COL4A2	Likely pathogenic	criteria provided, single submitter
1685278	NM_001846.4(COL4A2):c.3346+1G>A	COL4A2	Likely pathogenic	criteria provided, single submitter
1703695	NM_001846.4(COL4A2):c.3634G>A (p.Gly1212Ser)	COL4A2	Likely pathogenic	criteria provided, single submitter
1713186	NM_001846.4(COL4A2):c.4183C>T (p.Gln1395Ter)	COL4A2	Likely pathogenic	criteria provided, single submitter
2429006	NM_001846.4(COL4A2):c.2203+1G>C	COL4A2	Likely pathogenic	criteria provided, single submitter
2579161	NM_001846.4(COL4A2):c.4937G>C (p.Cys1646Ser)	COL4A2	Likely pathogenic	criteria provided, single submitter
3255139	NM_001846.4(COL4A2):c.2453G>T (p.Gly818Val)	COL4A2	Likely pathogenic	criteria provided, single submitter
3255204	NM_001846.4(COL4A2):c.2687G>A (p.Gly896Glu)	COL4A2	Likely pathogenic	criteria provided, single submitter
3392554	NM_001846.4(COL4A2):c.3950G>T (p.Gly1317Val)	COL4A2	Likely pathogenic	criteria provided, single submitter
3770213	NM_001846.4(COL4A2):c.1485del (p.Pro496fs)	COL4A2	Likely pathogenic	criteria provided, single submitter
3770218	NM_001846.4(COL4A2):c.3191del (p.Gly1064fs)	COL4A2	Likely pathogenic	criteria provided, single submitter
3775800	NM_001846.4(COL4A2):c.2264dup (p.Gly756fs)	COL4A2	Likely pathogenic	criteria provided, single submitter
444321	NM_001846.4(COL4A2):c.4357G>T (p.Gly1453Ter)	COL4A2	Likely pathogenic	criteria provided, single submitter
4688005	NM_001846.4(COL4A2):c.1189+1G>A	COL4A2	Likely pathogenic	criteria provided, single submitter
4813470	NM_001846.4(COL4A2):c.4038del (p.Arg1349fs)	COL4A2	Likely pathogenic	criteria provided, single submitter
4820092	NM_001846.4(COL4A2):c.2249G>A (p.Gly750Asp)	COL4A2	Likely pathogenic	criteria provided, single submitter
807561	NM_001846.4(COL4A2):c.1856G>A (p.Gly619Asp)	COL4A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
864858	NM_001846.4(COL4A2):c.2902+1G>A	COL4A2	Likely pathogenic	criteria provided, single submitter
996003	NM_001846.4(COL4A2):c.4151_4168del (p.Thr1384_Gly1389del)	COL4A2	Likely pathogenic	criteria provided, single submitter
1096634	NM_001846.4(COL4A2):c.4208C>A (p.Thr1403Lys)	COL4A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1172813	NM_001846.4(COL4A2):c.4049G>A (p.Gly1350Asp)	COL4A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 12 · 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
COL4A2	Strong	Autosomal dominant	brain small vessel disease 2A, autosomal dominant	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL4A2	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A2	Orphanet:99810	Familial porencephaly
COL4A1	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A1	Orphanet:477749	Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1	Orphanet:481986	Familial schizencephaly
COL4A1	Orphanet:73229	HANAC syndrome
COL4A1	Orphanet:75326	Familial isolated retinal arteriolar tortuosity
COL4A1	Orphanet:899	Walker-Warburg syndrome
COL4A1	Orphanet:99810	Familial porencephaly
COL4A4	Orphanet:653722	Digenic Alport syndrome
COL4A4	Orphanet:88918	Autosomal dominant Alport syndrome
COL4A4	Orphanet:88919	Autosomal recessive Alport syndrome

Cohort genes → proteins

5 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL4A2	HGNC:2203	ENSG00000134871	P08572	Collagen alpha-2(IV) chain	gencc,clinvar
COL4A1	HGNC:2202	ENSG00000187498	P02462	Collagen alpha-1(IV) chain	clinvar
COL4A4	HGNC:2206	ENSG00000081052	P53420	Collagen alpha-4(IV) chain	clinvar
COL4A2-AS2	HGNC:39849	ENSG00000224821		COL4A2 antisense RNA 2	clinvar
COL4A2-AS1	HGNC:40156	ENSG00000232814		COL4A2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL4A2	Collagen alpha-2(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A1	Collagen alpha-1(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
COL4A4	Collagen alpha-4(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 5 · 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	5	1.8×	0.054

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL4A2	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A1	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A4	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
COL4A2-AS2	Other/Unknown	no
COL4A2-AS1	Other/Unknown	no

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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
placenta	2
decidua	1
saphenous vein	1
right coronary artery	1
visceral pleura	1
metanephros cortex	1
pigmented layer of retina	1
renal medulla	1
skeletal muscle tissue	1
subcutaneous adipose tissue	1
sural nerve	1
left coronary artery	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL4A2	284	ubiquitous	marker	saphenous vein, decidua, placenta
COL4A1	283	ubiquitous	marker	visceral pleura, placenta, right coronary artery
COL4A4	187	broad	marker	renal medulla, metanephros cortex, pigmented layer of retina
COL4A2-AS2	97	tissue_specific	yes	sural nerve, skeletal muscle tissue, subcutaneous adipose tissue
COL4A2-AS1	123		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left coronary artery

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A1	2,909
COL4A2	2,746
COL4A4	1,243
COL4A2-AS2	0
COL4A2-AS1	0

Intra-cohort edges

A	B	Sources
COL4A1	COL4A2	intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL4A2	P08572	4
COL4A1	P02462	4
COL4A4	P53420	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 5 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
Anchoring fibril formation	3	761.3×	2e-08	COL4A2, COL4A1, COL4A4
Fibronectin matrix formation	3	571.0×	2e-08	COL4A2, COL4A1, COL4A4
Crosslinking of collagen fibrils	3	571.0×	2e-08	COL4A2, COL4A1, COL4A4
Attachment of bacteria to epithelial cells	3	496.5×	3e-08	COL4A2, COL4A1, COL4A4
Laminin interactions	3	380.7×	5e-08	COL4A2, COL4A1, COL4A4
Collagen chain trimerization	3	259.6×	1e-07	COL4A2, COL4A1, COL4A4
Signaling by PDGF	3	253.8×	1e-07	COL4A2, COL4A1, COL4A4
NCAM1 interactions	3	248.3×	1e-07	COL4A2, COL4A1, COL4A4
Assembly of collagen fibrils and other multimeric structures	3	200.3×	2e-07	COL4A2, COL4A1, COL4A4
Collagen degradation	3	175.7×	3e-07	COL4A2, COL4A1, COL4A4
Collagen biosynthesis and modifying enzymes	3	170.4×	3e-07	COL4A2, COL4A1, COL4A4
Non-integrin membrane-ECM interactions	3	154.3×	3e-07	COL4A2, COL4A1, COL4A4
ECM proteoglycans	3	150.3×	3e-07	COL4A2, COL4A1, COL4A4
Integrin cell surface interactions	3	134.3×	4e-07	COL4A2, COL4A1, COL4A4
Scavenging by Class A Receptors	2	400.7×	8e-06	COL4A2, COL4A1

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
collagen fibril organization	3	224.7×	2e-06	COL4A2, COL4A1, COL4A4
collagen-activated tyrosine kinase receptor signaling pathway	2	864.2×	2e-05	COL4A2, COL4A1
renal tubule morphogenesis	1	1404.3×	0.005	COL4A1
retinal blood vessel morphogenesis	1	802.5×	0.006	COL4A1
glomerular basement membrane development	1	510.7×	0.007	COL4A4
blood vessel morphogenesis	1	267.5×	0.011	COL4A1
branching involved in blood vessel morphogenesis	1	175.5×	0.011	COL4A1
neuromuscular junction development	1	175.5×	0.011	COL4A1
basement membrane organization	1	170.2×	0.011	COL4A1
endodermal cell differentiation	1	165.2×	0.011	COL4A2
response to activity	1	108.0×	0.015	COL4A2
cellular response to amino acid stimulus	1	102.1×	0.015	COL4A1
cellular response to transforming growth factor beta stimulus	1	92.1×	0.016	COL4A2
DNA-templated transcription	1	74.9×	0.018	COL4A2
epithelial cell differentiation	1	58.5×	0.021	COL4A1
negative regulation of angiogenesis	1	56.2×	0.021	COL4A2
extracellular matrix organization	1	40.7×	0.027	COL4A2
brain development	1	26.5×	0.039	COL4A1
angiogenesis	1	20.8×	0.047	COL4A2

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 5 evidence-associated genes (60%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL4A2	0	0
COL4A1	0	0
COL4A4	0	0
COL4A2-AS2	0	0
COL4A2-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	COL4A2, COL4A1, COL4A4, COL4A2-AS2, COL4A2-AS1

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)
COL4A2	0	—
COL4A1	0	—
COL4A4	0	—
COL4A2-AS2	0	—
COL4A2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.