COL4A2

Summary

COL4A2 (collagen type IV alpha 2 chain, HGNC:2203) is a protein-coding gene on chromosome 13q34, encoding Collagen alpha-2(IV) chain (P08572). 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.

This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter.

Source: NCBI Gene 1284 — RefSeq curated summary.

At a glance

• Gene–disease (curated): brain small vessel disease 2A, autosomal dominant (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 59
• Clinical variants (ClinVar): 1,816 total — 39 pathogenic, 46 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes
• MANE Select transcript: NM_001846

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2203
Approved symbol	COL4A2
Name	collagen type IV alpha 2 chain
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22259, DKFZp686I14213
Ensembl gene	ENSG00000134871
Ensembl biotype	protein_coding
OMIM	120090
Entrez	1284

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 18 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000360467, ENST00000400163, ENST00000462309, ENST00000463084, ENST00000478681, ENST00000480609, ENST00000480771, ENST00000483683, ENST00000494852, ENST00000617564, ENST00000619688, ENST00000648222, ENST00000649101, ENST00000649396, ENST00000649951, ENST00000650225, ENST00000650322, ENST00000650540, ENST00000714396, ENST00000714397, ENST00000714398, ENST00000714399, ENST00000907571, ENST00000907572, ENST00000907573, ENST00000907574, ENST00000907575, ENST00000907576, ENST00000907577

RefSeq mRNA: 1 — MANE Select: NM_001846 NM_001846

CCDS: CCDS41907

Canonical transcript exons

ENST00000360467 — 48 exons

Exon	Start	End
ENSE00001345173	110357472	110357552
ENSE00003507335	110307860	110307947
ENSE00003542495	110308069	110308123
ENSE00003832854	110424734	110424868
ENSE00004023805	110492070	110492177
ENSE00004023806	110439789	110439833
ENSE00004023807	110449679	110449789
ENSE00004023808	110458771	110458934
ENSE00004023809	110503383	110503481
ENSE00004023810	110438618	110438668
ENSE00004023811	110472929	110473150
ENSE00004023813	110489711	110489785
ENSE00004023814	110467040	110467096
ENSE00004023815	110504148	110504264
ENSE00004023816	110438002	110438037
ENSE00004023817	110485655	110485836
ENSE00004023818	110450305	110450454
ENSE00004023819	110503847	110503993
ENSE00004023820	110424953	110424997
ENSE00004023822	110506415	110506606
ENSE00004023823	110484905	110485027
ENSE00004023824	110429885	110429956
ENSE00004023825	110445829	110445882
ENSE00004023826	110436269	110436367
ENSE00004023827	110430401	110430436
ENSE00004023828	110495342	110495467
ENSE00004023829	110446798	110446864
ENSE00004023831	110432325	110432360
ENSE00004023833	110489445	110489508
ENSE00004023835	110493211	110493282
ENSE00004023836	110430545	110430607
ENSE00004023837	110434401	110434442
ENSE00004023838	110501668	110501784
ENSE00004023839	110457343	110457435
ENSE00004023840	110507935	110508221
ENSE00004023841	110480220	110480390
ENSE00004023842	110465405	110465606
ENSE00004023845	110462278	110462384
ENSE00004023846	110503121	110503282
ENSE00004023847	110466003	110466062
ENSE00004023848	110469217	110469324
ENSE00004023849	110428467	110428583
ENSE00004023850	110482516	110482659
ENSE00004023851	110491233	110491340
ENSE00004023853	110307284	110307528
ENSE00004023854	110478003	110478164
ENSE00004023855	110462114	110462186
ENSE00004023856	110511934	110513209

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 88.4305 / max 1891.2526, expressed in 1371 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136042	77.2532	1252
136041	9.5508	1139
136058	0.6249	342
136048	0.2723	147
136057	0.1887	38
136038	0.1858	98
136055	0.1383	53
136039	0.0951	46
136056	0.0468	28
136053	0.0411	10

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.89	gold quality
decidua	UBERON:0002450	99.77	gold quality
placenta	UBERON:0001987	99.71	gold quality
pericardium	UBERON:0002407	99.71	gold quality
visceral pleura	UBERON:0002401	99.62	gold quality
stromal cell of endometrium	CL:0002255	99.61	gold quality
urethra	UBERON:0000057	99.58	gold quality
right coronary artery	UBERON:0001625	99.58	gold quality
blood vessel layer	UBERON:0004797	99.51	gold quality
coronary artery	UBERON:0001621	99.47	gold quality
ascending aorta	UBERON:0001496	99.45	gold quality
thoracic aorta	UBERON:0001515	99.45	gold quality
left coronary artery	UBERON:0001626	99.44	gold quality
descending thoracic aorta	UBERON:0002345	99.42	gold quality
aorta	UBERON:0000947	99.41	gold quality
pylorus	UBERON:0001166	99.40	gold quality
cardia of stomach	UBERON:0001162	99.39	gold quality
popliteal artery	UBERON:0002250	99.37	gold quality
tibial artery	UBERON:0007610	99.37	gold quality
myometrium	UBERON:0001296	99.36	gold quality
renal medulla	UBERON:0000362	99.35	gold quality
vena cava	UBERON:0004087	99.32	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.28	gold quality
lower esophagus	UBERON:0013473	99.27	gold quality
colonic epithelium	UBERON:0000397	99.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.22	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.15	gold quality
mucosa of stomach	UBERON:0001199	99.12	gold quality
layer of synovial tissue	UBERON:0007616	99.11	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.11	gold quality

Single-cell (SCXA)

Detected in 34 experiment(s), a significant marker in 32.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	2725.58
E-GEOD-84465	yes	2377.33
E-GEOD-130473	yes	2105.08
E-MTAB-8410	yes	1582.64
E-CURD-112	yes	1289.78
E-MTAB-9067	yes	1269.76
E-MTAB-9906	yes	979.95
E-MTAB-7407	yes	785.41
E-ANND-5	yes	574.99
E-GEOD-83139	yes	397.80
E-MTAB-6108	yes	295.92
E-MTAB-3929	yes	277.60
E-ENAD-27	yes	265.52
E-GEOD-81608	yes	251.40
E-MTAB-7249	yes	151.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, FOXO1, SOX9, SRY, VHL

miRNA regulators (miRDB)

62 targeting COL4A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607

Literature-anchored findings (GeneRIF, showing 40)

• an imbalance of glomerular alpha2(IV) and alpha5(IV) chain expression occurred in IgA nephropathy (PMID:12021518)
• Data show that the NC1 but not 7S domain is essential for chain association and initiation of triple helix formation in human collagen alpha2(IV) . (PMID:15522229)
• alpha2(IV)NC1 domain has a role in regulating tumor cell behavior (PMID:15743801)
• Mutation does not represent a further major genetic locus for thin basement membrane nephropathy. (PMID:17216253)
• Comparison of alpha5(IV) with alpha2(IV) expression in Alport patients is simple and eliminates technical artifacts. (PMID:17554254)
• support a crucial role for angiogenesis inhibitors in shifting the fate of radiation-induced HIF-1alpha activity from hypoxia-induced tumor radioresistance to hypoxia-induced tumor apoptosis (PMID:17557121)
• In mildly inflamed synovium from trauma patients, collagen alpha1/2(IV) chains were strongly present. (PMID:18050191)
• The co-detection of alpha5 and alpha2 chains of collagen IV in frozen skin biopsies is therefore proposed as a simple technique to diagnose Alport syndrome. (PMID:18706356)
• E1B-55kD-deleted oncolytic adenovirus armed with canstatin gene yields an enhanced anti-tumor efficacy on pancreatic cancer. (PMID:19481338)
• Data showed that miR-29a negatively regulated collagen IV by directly targeting the 3’UTRs of col4a1 and col4a2. (PMID:20067797)
• COL4A2 was overexpressed in the ER-negative breast cancer group. (PMID:20805453)
• Screening of COL4A1 and COL4A2 revealed numerous alterations in coding and non-coding regions of both genes in keratoconus patients. None of the identified sequence variants completely segregated with the affected keratoconus phenotype. (PMID:21527998)
• this study confirmed that abnormalities of the alpha1alpha1alpha2 heterotrimers of type IV collagen cause porencephaly and stresses the importance of screening for COL4A2 as well as for COL4A1. (PMID:22209246)
• The data suggested that COL4A2 mutations impair COL4A1 and COL4A2 secretion and can also result in cytotoxicity. The findings also suggested that, collectively, mutations in COL4A1 and COL4A2 contribute to sporadic cases of intracerebral hemorrhage. (PMID:22209247)
• dominant COL4A2 mutations are a novel major risk factor for familial cerebrovascular disease, including porencephaly and small-vessel disease with reduced penetrance and variable phenotype, which might also be modified by other contributing factors. (PMID:22333902)
• The expression of collagen type IV and its alpha chains (alpha1-6) was investigated in different endothelial cell culture systems in vitro qualitatively and quantitatively. (PMID:23551189)
• Data indicate that the aberrantly methylated and expressed genes in cancer process including IRS1 and collagen-related genes COL4A1, COL4A2 and COL6A3. (PMID:23818951)
• The whole exome sequencing showed no pathological mutations of COL4A1 and COL4A2 in fetal intraventricular hemorrhage (PMID:24317722)
• Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression. (PMID:24503185)
• Reduction of COL4A2 expression by RNAI-mediated knockdown induces cell death. Finally, elevated Notch3 expression levels correlate with higher COL4A2 expression in human ovarian tumor specimens (PMID:25169943)
• An association was found between common variation in the COL4A2 gene and sporadic cerebral small vessel disease. (PMID:25653287)
• Studied the role of alpha1 and alpha2 chains of type IV collagen in UIP; found type IV collagen deposition in early fibrotic lesions of UIP may be implicated in refractory pathophysiology including migration of lesion fibroblasts via a FAK pathway. (PMID:26006016)
• analysis of the unique AAB composition and chain register for a heterotrimeric type IV collagen model peptide COL4a1/COL4a2 containing a natural interruption site (PMID:26209635)
• SMAD3 is a necessary factor for TGFbeta-mediated stimulation of mRNA and protein expression of type IV collagen genes in human vascular smooth muscle cells; it regulates expression of COL4a1 and COL4a2 (PMID:26310581)
• No significant change in canstatin levels was observed between normotensive and pre-eclampsia patients. (PMID:26343951)
• identified a novel COL4A2 (c.2399G>A, p.G800E, CCDS41907.1) mutation in an autosomal dominant family with porencephaly and ocular abnormalities (PMID:26708157)
• These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, smooth muscle cells survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk. (PMID:27389912)
• Expression of miR-26a and miR-29a was significantly down regulated in leukoplakia and cancer tissues but up regulated in lichen planus tissues. Expression of target genes such as, ADAMTS7, ATP1B1, COL4A2, CPEB3, CDK6, DNMT3a and PI3KR1 was significantly down regulated in at least two of three disease types with respect to normal tissues. (PMID:27515006)
• Genotype-phenotype correlations in pathology caused by COL4A1 and COL4A2 mutations have been summarized. (Review) (PMID:27794444)
• Data showed that Col4A2 can restrain triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and MDA-MB-468 proliferation, migration, cell cycle, and ultimately lead to apoptosis. The data indicated that Col4A2 was significantly correlated with the proliferation and invasive potential of TNBC. (PMID:27906681)
• In this study, the inhibitory effect of recombinant canstatin on tumour growth was investigated using a gastric cancer xenograft model. (PMID:27919040)
• COL4A2 expression is significantly upregulated in human masticatory mucosa during wound healing (PMID:28005267)
• Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). (PMID:28542708)
• These results of this study provide evidence that the mutation of COL4A2 is associated with lacunar ischemic stroke and deep intracerebral hemorrhage. (PMID:28954878)
• Our study further emphasizes the need to search for both COL4A1 and COL4A2 mutations in children presenting with uni- or bilateral polymicrogyria with schizencephaly, even in the absence of intracranial microbleeds, calcification or associated systemic features. (PMID:30315939)
• Here, we set out to determine the efficacy of PBA as a treatment for adult COL4A1/4A2 pathologies. Our data establish that reducing ER stress is a therapeutic avenue for preventing and treating established adult ICH, but is not for effective eye and renal pathologies and can be counter-indicative for pathologies due to BM defects as it reduces their ability to withstand mechanical stress. (PMID:30351356)
• COL4A1/COL4A2 mutations typically cause a severe neurologic condition and a broader spectrum of milder phenotypes, in which epilepsy is the predominant feature. (PMID:30413629)
• Our results indicated that NID2, COL4A1 and COL4A2 could be the potential novel biomarkers for gastric cancer diagnosis prognosis and the promising therapeutic targets (PMID:30975489)
• rs3803230 and rs76425569 showed significant association with the risk of lacunar stroke in Xinjiang Han population. (PMID:31214923)
• Wnt/beta-catenin pathway was found to play an important role in the negative regulation of osteogenesis through COL4A2. (PMID:31285761)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	col4a2	ENSDARG00000104110
mus_musculus	Col4a2	ENSMUSG00000031503
rattus_norvegicus	Col4a2	ENSRNOG00000023972

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL1A1 (ENSG00000108821), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), COL18A1 (ENSG00000182871), EMID1 (ENSG00000186998), COL4A1 (ENSG00000187498), COL4A5 (ENSG00000188153), COL25A1 (ENSG00000188517), COL27A1 (ENSG00000196739), COL13A1 (ENSG00000197467), COL4A6 (ENSG00000197565), COL11A2 (ENSG00000204248), COL5A2 (ENSG00000204262), COL15A1 (ENSG00000204291), COLQ (ENSG00000206561), COL28A1 (ENSG00000215018)

Protein

Protein identifiers

Collagen alpha-2(IV) chain — P08572 (reviewed: P08572)

All UniProt accessions (13): A0A087WY39, A0A3B3IRV2, A0A3B3IS04, A0A3B3IS47, A0A3B3IT80, A0A3B3ITN7, P08572, A0A3B3ITQ8, A0AAQ5BHW7, A0AAQ5BHY3, A0AAQ5BHY9, A0AAQ5BI49, A2A352

UniProt curated annotations — full annotation on UniProt →

Function. 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. Canstatin, a cleavage product corresponding to the collagen alpha 2(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity. It inhibits proliferation and migration of endothelial cells, reduces mitochondrial membrane potential, and induces apoptosis. Specifically induces Fas-dependent apoptosis and activates procaspase-8 and -9 activity. Ligand for alphavbeta3 and alphavbeta5 integrins.

Subunit / interactions. There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. Interacts with EFEMP2.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Post-translational modifications. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens. The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues. Proteolytic processing produces the C-terminal NC1 peptide, canstatin.

Disease relevance. Brain small vessel disease 2 (BSVD2) [MIM:614483] An autosomal dominant cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD2 features include intracranial hemorrage, fluid-filled cysts or cavities within the cerebral hemispheres, delayed psychomotor development, hemiplegia, spasticity and seizures. The disease is caused by variants affecting the gene represented in this entry. Intracerebral hemorrhage (ICH) [MIM:614519] A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.

Similarity. Belongs to the type IV collagen family.

RefSeq proteins (1): NP_001837* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001442	Collagen_IV_NC	Domain
IPR008160	Collagen	Repeat
IPR016187	CTDL_fold	Homologous_superfamily
IPR036954	Collagen_IV_NC_sf	Homologous_superfamily
IPR050149	Collagen_superfamily	Family

Pfam: PF01391, PF01413

UniProt features (85 total): strand 21, compositionally biased region 18, sequence variant 13, sequence conflict 7, region of interest 6, disulfide bond 6, helix 5, chain 2, turn 2, signal peptide 1, propeptide 1, modified residue 1, glycosylation site 1, domain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1LI1	X-RAY DIFFRACTION	1.9
6MPX	X-RAY DIFFRACTION	1.9
5NB2	X-RAY DIFFRACTION	2.5
5NAX	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08572-F1	47.97	0.13

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 1490

Disulfide bonds (6): 1504–1593, 1537–1590, 1549–1555, 1612–1708, 1646–1705, 1658–1665

Glycosylation sites (1): 138

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1566977	Fibronectin matrix formation
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-186797	Signaling by PDGF
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-216083	Integrin cell surface interactions
R-HSA-2214320	Anchoring fibril formation
R-HSA-2243919	Crosslinking of collagen fibrils
R-HSA-3000157	Laminin interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-3000480	Scavenging by Class A Receptors
R-HSA-419037	NCAM1 interactions
R-HSA-8948216	Collagen chain trimerization
R-HSA-9638630	Attachment of bacteria to epithelial cells

MSigDB gene sets: 390 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOCC_COLLAGEN_TRIMER, DITTMER_PTHLH_TARGETS_UP, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, PATIL_LIVER_CANCER, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (9): angiogenesis (GO:0001525), DNA-templated transcription (GO:0006351), response to activity (GO:0014823), negative regulation of angiogenesis (GO:0016525), extracellular matrix organization (GO:0030198), collagen fibril organization (GO:0030199), endodermal cell differentiation (GO:0035987), collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063), cellular response to transforming growth factor beta stimulus (GO:0071560)

GO Molecular Function (4): extracellular matrix structural constituent (GO:0005201), extracellular matrix structural constituent conferring tensile strength (GO:0030020), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), collagen type IV trimer (GO:0005587), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), collagen trimer (GO:0005581), basement membrane (GO:0005604)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Extracellular matrix organization	5
Collagen formation	2
Assembly of collagen fibrils and other multimeric structures	2
Degradation of the extracellular matrix	1
Signaling by Receptor Tyrosine Kinases	1
Binding and Uptake of Ligands by Scavenger Receptors	1
NCAM signaling for neurite out-growth	1
Collagen biosynthesis and modifying enzymes	1
Biofilm formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular matrix	2
binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
gene expression	1
RNA biosynthetic process	1
response to stimulus	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
extracellular structure organization	1
external encapsulating structure organization	1
extracellular matrix organization	1
endoderm formation	1
cell differentiation	1
cell surface receptor protein tyrosine kinase signaling pathway	1
collagen-activated signaling pathway	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
structural molecule activity	1
extracellular matrix structural constituent	1
molecular_function	1
cellular anatomical structure	1
network-forming collagen trimer	1
chicken-wire-like collagen network	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1
extracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

2606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL4A2	COL4A1	P02462	961
COL4A2	NID1	P14543	765
COL4A2	COL5A2	P05997	749
COL4A2	LAMC1	P11047	747
COL4A2	LAMA4	Q16363	730
COL4A2	LAMA5	O15230	691
COL4A2	FN1	P02751	679
COL4A2	ITGA1	P56199	674
COL4A2	COL5A1	P20908	670
COL4A2	NID2	Q14112	649
COL4A2	LAMA2	P24043	649
COL4A2	F10	P00742	640
COL4A2	LAMA1	P25391	640
COL4A2	LAMA3	Q16787	636
COL4A2	TGFBI	Q15582	626

IntAct

66 interactions, top by confidence:

A	B	Type	Score
MMP9	TIMP1	psi-mi:“MI:0914”(association)	0.640
MMP2	COL4A1	psi-mi:“MI:0914”(association)	0.640
COL4A1	COL4A2	psi-mi:“MI:0407”(direct interaction)	0.560
COL10A1	C1QL1	psi-mi:“MI:0914”(association)	0.530
IFNA21	IFIT3	psi-mi:“MI:0914”(association)	0.530
COLGALT2	COL1A1	psi-mi:“MI:0914”(association)	0.530
LYG2	COL4A2	psi-mi:“MI:0914”(association)	0.530
FKBP9	CASC3	psi-mi:“MI:0914”(association)	0.530
PLOD3	COL4A1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LAIR2	LAMA5	psi-mi:“MI:0914”(association)	0.530
PLOD3	PLOD2	psi-mi:“MI:0914”(association)	0.530
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
COL4A2	KLK6	psi-mi:“MI:0570”(protein cleavage)	0.440
COL4A1	COL4A1	psi-mi:“MI:0195”(covalent binding)	0.440
COL4A2	ARMS2	psi-mi:“MI:0915”(physical association)	0.370
COL4A2	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
CSNK2B	COL4A2	psi-mi:“MI:0915”(physical association)	0.370
COL4A2	DAZAP2	psi-mi:“MI:0915”(physical association)	0.370
COL4A2	TENT5A	psi-mi:“MI:0915”(physical association)	0.370
COL4A2	SKIL	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	COL4A2	psi-mi:“MI:0915”(physical association)	0.370
COL4A2	SMN1	psi-mi:“MI:0915”(physical association)	0.370
TK1	COL4A2	psi-mi:“MI:0915”(physical association)	0.370
	COL4A2	psi-mi:“MI:0915”(physical association)	0.370
NA	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (74): COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), TNPO3 (Co-fractionation)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WR59, C0HLN2, C7DZK3, O35167, O35348, O76368, O88207, P08122, P08572, P12106, P12107, P12108, P13942, P20849, P20850, P20908, P20909, P25067, P25940, P53420, P83371, P98085, Q01955, Q03637, Q05722, Q07092, Q07643, Q0VF58, Q14031, Q14055, Q14993, Q17RW2, Q28083, Q30D77, Q32S24, Q4ZJM7

Diamond homologs: P02462, P02463, P08120, P08122, P08572, P17139, P17140, P27393, P29400, P53420, P55787, Q01955, Q14031, Q28084, Q28247, Q29442, Q7SIB2, Q7SIB3, Q9QZR9, Q9QZS0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	COL4A2	“transcriptional regulation”
COL4A2	“up-regulates activity”	“A2/b1 integrin”	binding
COL4A2	up-regulates	ECM_synthesis
COL4A2	“up-regulates activity”	“A1/b1 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Collagen biosynthesis and modifying enzymes	13	45.2×	1e-16
Collagen chain trimerization	7	37.1×	4e-08
Collagen degradation	8	28.7×	3e-08
Assembly of collagen fibrils and other multimeric structures	6	24.5×	8e-06
Non-integrin membrane-ECM interactions	5	15.8×	7e-04
Integrin cell surface interactions	5	13.7×	1e-03
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	5	8.8×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	8	30.5×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

1816 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	39
Likely pathogenic	46
Uncertain significance	718
Likely benign	509
Benign	285

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1041965	NM_001846.4(COL4A2):c.3448C>T (p.Gln1150Ter)	Pathogenic
1074537	NM_001846.4(COL4A2):c.3634+1G>A	Pathogenic
1299561	NM_001846.4(COL4A2):c.1011+1G>A	Pathogenic
1352073	NM_001846.4(COL4A2):c.3882_3891dup (p.Pro1298fs)	Pathogenic
1389768	NM_001846.4(COL4A2):c.2032C>T (p.Gln678Ter)	Pathogenic
1395887	NM_001846.4(COL4A2):c.1545_1546del (p.Asp516fs)	Pathogenic
1712742	NM_001846.4(COL4A2):c.3272G>A (p.Gly1091Asp)	Pathogenic
1905712	NM_001846.4(COL4A2):c.1864G>T (p.Gly622Ter)	Pathogenic
1913699	NM_001846.4(COL4A2):c.3466del (p.Gly1155_Leu1156insTer)	Pathogenic
1933149	NM_001846.4(COL4A2):c.546T>A (p.Tyr182Ter)	Pathogenic
1948893	NM_001846.4(COL4A2):c.1570_1571del (p.Gly524fs)	Pathogenic
1948910	NM_001846.4(COL4A2):c.1547del (p.Asp516fs)	Pathogenic
1952299	NM_001846.4(COL4A2):c.3766C>T (p.Arg1256Ter)	Pathogenic
2015130	NM_001846.4(COL4A2):c.1542dup (p.Gly515fs)	Pathogenic
2052696	NM_001846.4(COL4A2):c.4256delinsCG (p.Met1419fs)	Pathogenic
2098040	NM_001846.4(COL4A2):c.4698G>A (p.Trp1566Ter)	Pathogenic
2151150	NM_001846.4(COL4A2):c.1289dup (p.Arg431fs)	Pathogenic
2185412	NM_001846.4(COL4A2):c.799del (p.Val267fs)	Pathogenic
2770671	NM_001846.4(COL4A2):c.4095del (p.Asp1366fs)	Pathogenic
2805917	NM_001846.4(COL4A2):c.1311dup (p.Gly438fs)	Pathogenic
2809267	NM_001846.4(COL4A2):c.1359del (p.Gly454fs)	Pathogenic
2837937	NM_001846.4(COL4A2):c.439C>T (p.Gln147Ter)	Pathogenic
2844624	NM_001846.4(COL4A2):c.2446del (p.Met816fs)	Pathogenic
2847390	NM_001846.4(COL4A2):c.1507_1513del (p.Gly503fs)	Pathogenic
2851323	NM_001846.4(COL4A2):c.2262_2274dup (p.Gly759fs)	Pathogenic
2876988	NM_001846.4(COL4A2):c.1237G>T (p.Gly413Ter)	Pathogenic
29627	NM_001846.4(COL4A2):c.3455G>A (p.Gly1152Asp)	Pathogenic
29628	NM_001846.4(COL4A2):c.3110G>A (p.Gly1037Glu)	Pathogenic
3339986	NC_000013.10:g.(111138184_111141791)_(111156612_111158761)del	Pathogenic
374994	NM_001846.4(COL4A2):c.3490G>A (p.Gly1164Arg)	Pathogenic

SpliceAI

7556 predictions. Top by Δscore:

Variant	Effect	Δscore
13:110306939:CTCA:C	donor_loss	1.0000
13:110306940:TCA:T	donor_loss	1.0000
13:110306941:CA:C	donor_loss	1.0000
13:110306942:A:AC	donor_gain	1.0000
13:110306942:A:T	donor_loss	1.0000
13:110306943:C:CC	donor_gain	1.0000
13:110306943:C:CG	donor_loss	1.0000
13:110306943:CCTT:C	donor_gain	1.0000
13:110307856:CTA:C	acceptor_loss	1.0000
13:110307858:A:AG	acceptor_gain	1.0000
13:110307858:AGGC:A	acceptor_loss	1.0000
13:110307859:G:GG	acceptor_gain	1.0000
13:110307944:GGCG:G	donor_gain	1.0000
13:110307945:GCG:G	donor_gain	1.0000
13:110307945:GCGG:G	donor_gain	1.0000
13:110307948:G:GG	donor_gain	1.0000
13:110307948:GTAAG:G	donor_loss	1.0000
13:110307949:T:G	donor_loss	1.0000
13:110308064:TGCA:T	acceptor_loss	1.0000
13:110308065:GCAG:G	acceptor_loss	1.0000
13:110308066:CA:C	acceptor_loss	1.0000
13:110308067:AG:A	acceptor_gain	1.0000
13:110308067:AGGT:A	acceptor_gain	1.0000
13:110308068:G:A	acceptor_loss	1.0000
13:110308068:GG:G	acceptor_gain	1.0000
13:110308068:GGTG:G	acceptor_gain	1.0000
13:110308120:GGCG:G	donor_gain	1.0000
13:110308121:GCG:G	donor_gain	1.0000
13:110308121:GCGG:G	donor_gain	1.0000
13:110308123:GGTA:G	donor_loss	1.0000

AlphaMissense

10791 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:110506558:A:C	S1516R	1.000
13:110506560:C:A	S1516R	1.000
13:110506560:C:G	S1516R	1.000
13:110507951:C:G	C1537W	1.000
13:110508036:T:A	W1566R	1.000
13:110508036:T:C	W1566R	1.000
13:110508038:G:C	W1566C	1.000
13:110508038:G:T	W1566C	1.000
13:110508040:T:C	L1567P	1.000
13:110508102:A:C	S1588R	1.000
13:110508104:C:A	S1588R	1.000
13:110508104:C:G	S1588R	1.000
13:110508108:T:C	C1590R	1.000
13:110508110:T:G	C1590W	1.000
13:110508174:T:A	C1612S	1.000
13:110508174:T:C	C1612R	1.000
13:110508175:G:A	C1612Y	1.000
13:110508175:G:C	C1612S	1.000
13:110508176:C:G	C1612W	1.000
13:110508200:G:C	W1620C	1.000
13:110508200:G:T	W1620C	1.000
13:110508205:G:A	G1622E	1.000
13:110508211:C:T	S1624F	1.000
13:110511985:A:C	S1645R	1.000
13:110511987:C:A	S1645R	1.000
13:110511987:C:G	S1645R	1.000
13:110511988:T:A	C1646S	1.000
13:110511988:T:C	C1646R	1.000
13:110511989:G:A	C1646Y	1.000
13:110511989:G:C	C1646S	1.000

dbSNP variants (sampled 300 via entrez): RS1000012551 (13:110405551 C>A,T), RS1000016430 (13:110512902 G>A), RS1000026632 (13:110436723 G>A), RS1000053215 (13:110484519 C>T), RS1000070513 (13:110398867 AT>A,ATT), RS1000071710 (13:110380853 A>G), RS1000105532 (13:110471291 T>C), RS1000108036 (13:110370665 C>T), RS1000112068 (13:110409033 C>G,T), RS1000119774 (13:110507265 C>G,T), RS1000127739 (13:110347544 G>A), RS1000180443 (13:110347764 A>G), RS1000184148 (13:110429602 G>A), RS1000194690 (13:110464340 C>T), RS1000195568 (13:110482779 A>C)

Disease associations

OMIM: gene MIM:120090 | disease phenotypes: MIM:614483, MIM:621414, MIM:614519, MIM:616471, MIM:617186, MIM:175780, MIM:607595

GenCC curated gene-disease

Disease	Classification	Inheritance
brain small vessel disease 2A, autosomal dominant	Strong	Autosomal dominant
COL4A1 or COL4A2-related cerebral small vessel disease	Moderate	Autosomal dominant
familial porencephaly	Supportive	Autosomal dominant

Mondo (14): brain small vessel disease 2A, autosomal dominant (MONDO:0013773), cerebral palsy (MONDO:0006497), brain small vessel disease 2B, autosomal recessive (MONDO:0980747), hemorrhage, intracerebral, susceptibility to (MONDO:0100533), intellectual disability (MONDO:0001071), myoepithelial tumor (MONDO:0002380), Bethlem myopathy 2 (MONDO:0034022), encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 (MONDO:0020781), hereditary ataxia (MONDO:0100309), brain small vessel disease 1 with or without ocular anomalies (MONDO:0008289), vasculitis (MONDO:0018882), vascular dementia (MONDO:0004648), (MONDO:0018788), familial porencephaly (MONDO:0020496)

Orphanet (10): Porencephaly (Orphanet:2940), Familial porencephaly (Orphanet:99810), COL4A1 or COL4A2-related cerebral small vessel disease (Orphanet:477759), Myopathic Ehlers-Danlos syndrome (Orphanet:536516), Bethlem muscular dystrophy (Orphanet:610), NAD(P)HX epimerase deficiency (Orphanet:555407), Hereditary ataxia (Orphanet:183518), COL4A1/2-related familial vascular leukoencephalopathy (Orphanet:36383), Vasculitis (Orphanet:52759), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000565	Esotropia
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001510	Growth delay
HP:0002069	Bilateral tonic-clonic seizure
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002126	Polymicrogyria
HP:0002132	Porencephalic cyst
HP:0002170	Intracranial hemorrhage
HP:0002197	Generalized-onset seizure
HP:0002273	Tetraparesis
HP:0002301	Hemiplegia
HP:0002392	EEG with polyspike wave complexes
HP:0002421	Poor head control
HP:0002445	Tetraplegia
HP:0002510	Spastic tetraplegia
HP:0002540	Inability to walk
HP:0003593	Infantile onset
HP:0003829	Typified by incomplete penetrance
HP:0007359	Focal-onset seizure
HP:0010636	Schizencephaly

GWAS associations

59 associations (top):

Study	Trait	p-value
GCST000998_11	Coronary heart disease	4.000000e-09
GCST001347_3	Coronary artery calcification	9.000000e-07
GCST002289_12	Coronary artery disease	2.000000e-06
GCST003013_29	White matter hyperintensity burden	7.000000e-07
GCST003116_31	Coronary artery disease	1.000000e-10
GCST003117_28	Myocardial infarction	8.000000e-08
GCST003542_144	Night sleep phenotypes	1.000000e-06
GCST003542_40	Night sleep phenotypes	1.000000e-06
GCST003542_75	Night sleep phenotypes	8.000000e-06
GCST004787_57	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	4.000000e-10
GCST005194_54	Coronary artery disease	4.000000e-17
GCST005194_55	Coronary artery disease	6.000000e-24
GCST005195_130	Coronary artery disease	4.000000e-23
GCST005196_2	Coronary artery disease	6.000000e-24
GCST005984_63	Glomerular filtration rate	1.000000e-08
GCST006612_122	LDL cholesterol	5.000000e-12
GCST006614_107	Total cholesterol levels	5.000000e-13
GCST007016_12	Serum bilirubin levels x sex interaction in metabolic syndrome	8.000000e-06
GCST007094_122	Diastolic blood pressure	6.000000e-09
GCST007846_5	Arterial stiffness	2.000000e-07
GCST008062_127	Blood urea nitrogen levels	4.000000e-08
GCST008403_27	Arterial stiffness index	1.000000e-07
GCST008762_10	Intake of sweets	7.000000e-06
GCST008873_1	Non-lobar intracerebral hemorrhage	3.000000e-07
GCST008876_2	Non-lobar intracerebral hemorrhage (MTAG)	5.000000e-10
GCST009210_6	Middle temporal gyrus volume	5.000000e-06
GCST009420_1	Retinal arteriolar tortuosity	5.000000e-12
GCST009421_2	Maximum retinal arteriolar tortuosity	7.000000e-07
GCST010101_11	White matter hyperintensities	8.000000e-11
GCST010204_61	Low density lipoprotein cholesterol levels	2.000000e-09

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0005665	white matter hyperintensity measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004570	bilirubin measurement
EFO:0008343	sex interaction measurement
EFO:0006336	diastolic blood pressure
EFO:0004517	arterial stiffness measurement
EFO:0010158	sugar consumption measurement
EFO:0010178	non-lobar intracerebral hemorrhage
EFO:0010554	retinal vasculature measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0006834	septic shock
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0004533	alkaline phosphatase measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009208	Myoepithelioma	C04.557.435.585
D014657	Vasculitis	C14.907.940
C531642	Familial vascular leukoencephalopathy (supp.)
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364188 (PROTEIN COMPLEX GROUP)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

73 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	7
bisphenol A	decreases methylation, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Tobacco Smoke Pollution	decreases expression, decreases methylation, affects expression	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	decreases methylation, increases methylation, affects expression	3
chromium hexavalent ion	decreases expression, increases abundance	2
Cadmium	increases abundance, increases expression, decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Rotenone	decreases expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
Paclitaxel	affects cotreatment, decreases expression, increases expression	2
dicrotophos	increases expression	1
4-oxoretinoic acid	increases expression	1
testosterone enanthate	affects expression	1
apocarotenal	decreases expression	1
dimethylselenide	decreases expression, increases oxidation	1
beta-lapachone	increases expression, decreases expression	1
sodium bichromate	decreases expression	1
nickel subsulfide	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-oxoretinol	increases expression	1
beta-methylcholine	affects expression	1

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1NV	Abcam HeLa COL4A2 KO	Cancer cell line	Female
CVCL_D9C8	Ubigene HEK293 COL4A2 KO	Transformed cell line	Female
CVCL_E0AK	Ubigene HeLa COL4A2 KO	Cancer cell line	Female
CVCL_YX75	WMUi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
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