COL4A1

Summary

COL4A1 (collagen type IV alpha 1 chain, HGNC:2202) is a protein-coding gene on chromosome 13q34, encoding Collagen alpha-1(IV) chain (P02462). 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 a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1282 — RefSeq curated summary.

At a glance

• Gene–disease (curated): COL4A1-related disorder (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 51
• Clinical variants (ClinVar): 2,932 total — 146 pathogenic, 237 likely-pathogenic
• Phenotypes (HPO): 114
• Druggable target: yes
• MANE Select transcript: NM_001845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2202
Approved symbol	COL4A1
Name	collagen type IV alpha 1 chain
Location	13q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187498
Ensembl biotype	protein_coding
OMIM	120130
Entrez	1282

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 7 retained_intron, 2 nonsense_mediated_decay

ENST00000375820, ENST00000467182, ENST00000474391, ENST00000543140, ENST00000615732, ENST00000647632, ENST00000647797, ENST00000648170, ENST00000648695, ENST00000648966, ENST00000648989, ENST00000649484, ENST00000649720, ENST00000649738, ENST00000650115, ENST00000650138, ENST00000650424, ENST00000650566, ENST00000714329, ENST00000714330, ENST00000714331, ENST00000933607, ENST00000933608, ENST00000953813, ENST00000953814

RefSeq mRNA: 2 — MANE Select: NM_001845 NM_001303110, NM_001845

CCDS: CCDS76649, CCDS9511

Canonical transcript exons

ENST00000375820 — 52 exons

Exon	Start	End
ENSE00001351451	110187138	110187329
ENSE00001365411	110205353	110205406
ENSE00001366314	110200854	110200889
ENSE00001367184	110206865	110206891
ENSE00001368411	110186385	110186553
ENSE00001368589	110211647	110211673
ENSE00001368867	110195023	110195118
ENSE00001369972	110212574	110212618
ENSE00001371543	110213926	110214015
ENSE00001371609	110211869	110211922
ENSE00001372483	110209980	110210042
ENSE00001374078	110209392	110209427
ENSE00001375883	110201438	110201522
ENSE00001377683	110192830	110192913
ENSE00001378972	110210129	110210212
ENSE00001379642	110212417	110212479
ENSE00001380858	110205494	110205538
ENSE00001381957	110213782	110213826
ENSE00001382766	110203566	110203607
ENSE00001383389	110192214	110192284
ENSE00001384077	110206665	110206715
ENSE00001384920	110198467	110198631
ENSE00001385330	110208849	110208890
ENSE00001387152	110207403	110207489
ENSE00001388790	110242675	110242734
ENSE00003835175	110306944	110307157
ENSE00004023604	110162230	110162442
ENSE00004023605	110176424	110176513
ENSE00004023608	110178064	110178231
ENSE00004023609	110173900	110173998
ENSE00004023610	110176885	110177037
ENSE00004023611	110181292	110181389
ENSE00004023612	110163463	110163561
ENSE00004023613	110172720	110172770
ENSE00004023615	110176626	110176724
ENSE00004023616	110174623	110174749
ENSE00004023617	110166232	110166303
ENSE00004023618	110179271	110179421
ENSE00004023619	110182993	110183097
ENSE00004023620	110170547	110170732
ENSE00004023622	110177842	110177931
ENSE00004023623	110152334	110152506
ENSE00004023625	110155283	110155397
ENSE00004023626	110161192	110161369
ENSE00004023627	110169629	110169762
ENSE00004023628	110167158	110167230
ENSE00004023629	110148963	110150444
ENSE00004023630	110164862	110164990
ENSE00004023631	110175218	110175357
ENSE00004023632	110183184	110183276
ENSE00004023633	110178923	110179036
ENSE00004023634	110174446	110174526

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 128.3463 / max 2909.4252, expressed in 1262 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138237	125.9878	1260
138220	2.3064	654
138225	0.0521	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
visceral pleura	UBERON:0002401	99.77	gold quality
placenta	UBERON:0001987	99.62	gold quality
right coronary artery	UBERON:0001625	99.47	gold quality
decidua	UBERON:0002450	99.41	gold quality
stromal cell of endometrium	CL:0002255	99.33	gold quality
left coronary artery	UBERON:0001626	99.27	gold quality
coronary artery	UBERON:0001621	99.21	gold quality
colonic epithelium	UBERON:0000397	99.20	gold quality
blood vessel layer	UBERON:0004797	99.20	gold quality
popliteal artery	UBERON:0002250	99.12	gold quality
tibial artery	UBERON:0007610	99.12	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.10	gold quality
omental fat pad	UBERON:0010414	99.09	gold quality
peritoneum	UBERON:0002358	99.08	gold quality
aorta	UBERON:0000947	99.06	gold quality
adipose tissue	UBERON:0001013	99.01	gold quality
pleura	UBERON:0000977	98.99	gold quality
ascending aorta	UBERON:0001496	98.99	gold quality
thoracic aorta	UBERON:0001515	98.99	gold quality
saphenous vein	UBERON:0007318	98.99	gold quality
pericardium	UBERON:0002407	98.93	gold quality
descending thoracic aorta	UBERON:0002345	98.85	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.82	gold quality
upper lobe of lung	UBERON:0008948	98.73	gold quality
upper lobe of left lung	UBERON:0008952	98.71	gold quality
skin of hip	UBERON:0001554	98.69	gold quality
cauda epididymis	UBERON:0004360	98.69	gold quality
smooth muscle tissue	UBERON:0001135	98.65	gold quality
connective tissue	UBERON:0002384	98.65	gold quality
right lung	UBERON:0002167	98.61	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 29.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	4607.76
E-MTAB-8410	yes	2884.05
E-HCAD-23	yes	2368.14
E-GEOD-84465	yes	1956.59
E-CURD-112	yes	1710.94
E-MTAB-6308	yes	1503.35
E-GEOD-83139	yes	1203.59
E-MTAB-7407	yes	1102.12
E-MTAB-9906	yes	1025.74
E-ENAD-27	yes	1010.68
E-CURD-126	yes	817.10
E-MTAB-9067	yes	730.76
E-GEOD-81608	yes	661.39
E-MTAB-3929	yes	502.49
E-MTAB-8142	yes	137.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, LMX1B, MYC, RAMP2, TGFB1, TP53

miRNA regulators (miRDB)

49 targeting COL4A1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-3182	99.40	68.15	2454

Literature-anchored findings (GeneRIF, showing 40)

• The trimer-trimer interface is stabilized by the extensive hydrophobic and hydrophilic interactions without a need for disulfide cross-linking. (PMID:11970952)
• Modulation of triple-helical stability and subsequent melanoma cellular responses by single-site substitution of fluoroproline derivatives of collagen alpha1(IV). (PMID:11994000)
• CD44 interaction with the alpha 1(IV)1263-1277 region from basement membrane collagen is modulated by ligand glycosylation (PMID:12574156)
• Fibronectin and type IV collagen activate ERalpha AF-1 by the c-Src pathway in breast cancer (PMID:15467744)
• distinctive patterns of expression of the alpha1 (IV) and alpha5 (IV) collagen chains may be related to the histogenic sudoral origin of cyli (PMID:15583824)
• findings show that COL4A1 mutations segregate with porencephaly in human families; propose that Col4a1 mutations conspire with environmental trauma in causing the disease (PMID:15905400)
• Neonatal porencephaly and adult stroke related to mutations in collagen IV A1. (PMID:16374828)
• SDS-PAGE showed that the expressed arresten proteins were mainly inclusion bodies and had a molecular weight of 26 kDa. The expressed arresten protein showed evident biological activities. (PMID:16481288)
• Identified a COL4A1 mutation in a human family with small-vessel disease. Mutation of COL4A1 may cause a spectrum of cerebrovascular phenotypes and that persons with COL4A1 mutations may be predisposed to hemorrhage. (PMID:16598045)
• Mutation does not represent a further major genetic locus for thin basement membrane nephropathy. (PMID:17216253)
• Role of COL4A1 in cerebral microangiopathy. Phenotypic spectrum associated with mutations in this gene. (PMID:17696175)
• study found COL4A1 mutation carriers have great diversity in clinical expression of disease within the same family; some affected members may remain asymptomatic during years of follow-up & have no evidence of progression of vascular changes on brain MRI (PMID:17938367)
• In mildly inflamed synovium from trauma patients, collagen alpha1/2(IV) chains were strongly present. (PMID:18050191)
• Col-IV regulates the secretion of MMP-9 via a Src and FAK dependent pathway in MCF-7 cells (PMID:18061419)
• COL4A1 may be a candidate gene in unexplained familial syndromes with autosomal dominant hematuria, cystic kidney disease, intracranial aneurysms, and muscle cramps. (PMID:18160688)
• patients with breast cancer have elevated levels of collagen IV compared,Collagen IV may serve as a potential marker of tumour angiogenesis (PMID:18560403)
• The expression of LAMC2-COL4A1 genes were particularly effective in distinguishing OSCC from normal tissue. (PMID:18669583)
• Here we show that arresten, the 26-kDa non-collagenous domain of type IV collagen alpha1 chain, significantly increases apoptosis of endothelial cells in vitro by decreasing the amount of anti-apoptotic molecules of the Bcl-family; Bcl-2 and Bcl-xL. (PMID:18775695)
• Mutation of the COL4A1 gene appears to be a risk factor of antenatal intracerebral hemorrhage followed by porencephaly in the preterm newborn. (PMID:19194877)
• Results suggest that the down-regulation of alpha 6(IV) mRNA coincides with the acquisition of invasive growth properties, whereas alpha1(IV) and alpha1(VII) mRNAs were up-regulated already in dysplastic tissue. (PMID:19422682)
• dominantly inherited mutation in collagen (COL4A1) causing childhood onset stroke without porencephaly. (PMID:19477666)
• Examined association between COL4A1 SNPs and intracranial aneurysms in Japanese cohort. (PMID:19506372)
• study reports a rare variant in COL4A1 associated with intraventricular hemorrhage in dizygotic preterm twins (PMID:19840616)
• Data show that the expression of collagen types I, III and fibronectin was significantly higher in pancreatic cancer, and the expression of collagen type IV, laminin and vitronectin was significantly lower in pancreatic cancer. (PMID:19893454)
• The clinical heterogeneity of Cerebrovascular disease in the phenotypic expression of disorders related to COL4A1 mutations. (PMID:19949034)
• SNP rs3742207 in COL4A1 gene was significantly associated with arterial stiffness. (PMID:20031579)
• Data showed that miR-29a negatively regulated collagen IV by directly targeting the 3’UTRs of col4a1 and col4a2. (PMID:20067797)
• In COL4A1 stroke syndrome most mutations are missense mutations involving a glycine residue. (PMID:20166936)
• The COL4A1 mutations may be associated with various ophthalmologic developmental anomalies of anterior segment dysgenesis type. (PMID:20385946)
• Data show that occupancy of EPCR by protein C switches signaling specificity so that activation of PAR-1 by thrombin inhibits TNF-alpha-mediated synthesis of IL-6 and IL-8 and down-regulates TGF-beta-mediated expression of collagen type 4 and fibronectin. (PMID:20506163)
• Review. COL4A1 is a further cause of familial vasculopathy and may present with stroke, ischemic as well as hemorrhagic, in adult life and with radiological features of leukoaraiosis and microbleeds. (PMID:20558831)
• The restricted distribution of COL4A1 mutations within the CB3[IV] region is a characteristic of the reports of patients with hereditary angiopathy, aephropathy, aneurysms, and cramps. (PMID:20818663)
• review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations; COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype [review] (PMID:21157337)
• Sporadic COL4A1 mutations are associated with sporadic severe antenatal hemorrhagic stroke resembling hydranencephaly. (PMID:21357838)
• study describes 2 infants with a COL4A1 mutation and fetal intracerebral hemorrhages with posthemorrhagic ventricular dilatation on their fetal MRI (PMID:21500141)
• 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)
• identified putative heterozygous mutations in COL4A1 in two Muscle-eye-brain disease/Walker-Warburg syndrome patients (PMID:21625620)
• The corresponding human collagen IV-derived peptide (P290) co-precipitated with Legionella pneumophila Mip and competitively inhibited the Mip-collagen IV binding. (PMID:21794054)
• article describes 5 patients demonstrating intracranial calcification in whom a COL4A1 mutation has been identified. (PMID:22134833)
• 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)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	col4a1	ENSDARG00000055009
mus_musculus	Col4a1	ENSMUSG00000031502
rattus_norvegicus	Col4a1	ENSRNOG00000016281

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), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), COL18A1 (ENSG00000182871), EMID1 (ENSG00000186998), 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-1(IV) chain — P02462 (reviewed: P02462)

All UniProt accessions (13): A0A087WTY5, A0A3B3ISH5, A0A3B3ISV3, A0A3B3ISZ8, A0A3B3ITC8, A0A3B3ITG7, A0A3B3ITS9, A0A3B3IU02, A0A3B3IUD0, A0AAQ5BHV6, A0AAQ5BHW8, A0AAQ5BHX0, P02462

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. Arresten, comprising the C-terminal NC1 domain, inhibits angiogenesis and tumor formation. The C-terminal half is found to possess the anti-angiogenic activity. Specifically inhibits endothelial cell proliferation, migration and tube formation.

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.

Tissue specificity. Highly expressed in placenta.

Post-translational modifications. Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated. The modified lysines can be O-glycosylated. Contains 4-hydroxyproline. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. Contains 3-hydroxyproline. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline. 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 (sulfilimine cross-links) between Lys and Met residues. These cross-links are important for the mechanical stability of the basement membrane. Sulfilimine cross-link is catalyzed by PXDN. Proteolytic processing produces the C-terminal NC1 peptide, arresten.

Disease relevance. Hereditary angiopathy with nephropathy aneurysms and muscle cramps (HANAC) [MIM:611773] The clinical renal manifestations include hematuria and bilateral large cysts. Histologic analysis revealed complex basement membrane defects in kidney and skin. The systemic angiopathy appears to affect both small vessels and large arteries. The disease is caused by variants affecting the gene represented in this entry. Brain small vessel disease 1 with or without ocular anomalies (BSVD1) [MIM:175780] An autosomal dominant cerebrovascular disorder with variable manifestations reflecting the location and severity of the vascular defect. BSVD1 features include cerebral hemorrage, unilateral fluid-filled cysts or cavities within the cerebral hemispheres, leukoencephalopathy, hemiplegia, seizures, intellectual disability, and facial paresis. Affected individuals may manifest variable visual defects and ocular anomalies. 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. Tortuosity of retinal arteries (RATOR) [MIM:180000] A disease characterized by marked tortuosity of second- and third-order retinal arteries with normal first-order arteries and venous system. Most patients manifest variable degrees of symptomatic transient vision loss due to retinal hemorrhage following minor stress or trauma. The disease is caused by variants affecting the gene represented in this entry. Schizencephaly (SCHZC) [MIM:269160] Extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro-spinal fluid. The disease is caused by variants affecting the gene represented in this entry. Microangiopathy and leukoencephalopathy, pontine, autosomal dominant (PADMAL) [MIM:618564] A form of cerebral small vessel disease characterized by the recurrence of ischemic strokes starting in the thirties or forties, and associated with progressive imbalance and cognitive impairment. MRI examination shows ischemic lacunas in the pons and cerebral hemispheres, and diffuse leukoencephalopathy affecting various brain regions. The disease is caused by variants affecting the gene represented in this entry. Causative mutations affect a binding site for miR-29 microRNA located within the 3’UTR of COL4A1 and lead to an up-regulation of this gene.

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. NC1 domain mediates hexamerization of alpha chains of type IV collagen.

Similarity. Belongs to the type IV collagen family.

Isoforms (2)

UniProt ID	Names	Canonical?
P02462-1	1	yes
P02462-2	2

RefSeq proteins (2): NP_001290039, NP_001836* (*=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 (134 total): sequence variant 37, strand 20, compositionally biased region 19, sequence conflict 17, modified residue 15, helix 6, disulfide bond 6, region of interest 4, chain 2, cross-link 2, splice variant 2, signal peptide 1, propeptide 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5NAY	X-RAY DIFFRACTION	1.8
1LI1	X-RAY DIFFRACTION	1.9
6MPX	X-RAY DIFFRACTION	1.9
5NAX	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02462-F1	49.43	0.15

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 (17): 204, 207, 210, 587, 602, 603, 605, 606, 623, 626, 629, 632, 647, 1214, 1424, 1533, 1651

Disulfide bonds (6): 1460–1551, 1493–1548, 1505–1511, 1570–1665, 1604–1662, 1616–1622

Glycosylation sites (1): 126

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: 658 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_52, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOCC_COLLAGEN_TRIMER, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, PATIL_LIVER_CANCER, GTGCCTT_MIR506, MODULE_118

GO Biological Process (12): branching involved in blood vessel morphogenesis (GO:0001569), brain development (GO:0007420), neuromuscular junction development (GO:0007528), collagen fibril organization (GO:0030199), epithelial cell differentiation (GO:0030855), collagen-activated tyrosine kinase receptor signaling pathway (GO:0038063), blood vessel morphogenesis (GO:0048514), retinal blood vessel morphogenesis (GO:0061304), renal tubule morphogenesis (GO:0061333), cellular response to amino acid stimulus (GO:0071230), basement membrane organization (GO:0071711), angiogenesis (GO:0001525)

GO Molecular Function (4): extracellular matrix structural constituent (GO:0005201), extracellular matrix structural constituent conferring tensile strength (GO:0030020), platelet-derived growth factor binding (GO:0048407), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), collagen type IV trimer (GO:0005587), basement membrane (GO:0005604), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), collagen trimer (GO:0005581)

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
blood vessel morphogenesis	3
extracellular matrix organization	2
extracellular matrix	2
angiogenesis	1
branching morphogenesis of an epithelial tube	1
central nervous system development	1
animal organ development	1
head development	1
synapse organization	1
cell differentiation	1
epithelium development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
collagen-activated signaling pathway	1
blood vessel development	1
tube morphogenesis	1
retina vasculature morphogenesis in camera-type eye	1
epithelial tube morphogenesis	1
renal tubule development	1
response to amino acid	1
cellular response to acid chemical	1
anatomical structure formation involved in morphogenesis	1
structural molecule activity	1
extracellular matrix structural constituent	1
growth factor binding	1
binding	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
protein-containing complex	1

Protein interactions and networks

STRING

2814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL4A1	COL4A2	P08572	961
COL4A1	LAMC1	P11047	826
COL4A1	FN1	P02751	805
COL4A1	LAMB1	P07942	761
COL4A1	ITGA1	P56199	749
COL4A1	COL5A2	P05997	731
COL4A1	LAMA4	Q16363	725
COL4A1	NID1	P14543	723
COL4A1	COL5A1	P20908	715
COL4A1	LAMC2	Q13753	712
COL4A1	LAMA5	O15230	710
COL4A1	FBN1	P35555	709
COL4A1	MMP9	P14780	670
COL4A1	DDR1	Q08345	646
COL4A1	COL6A1	P12109	640

IntAct

48 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
COLGALT2	COL1A1	psi-mi:“MI:0914”(association)	0.530
PLOD3	COL4A1	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
KLK6	COL4A1	psi-mi:“MI:0570”(protein cleavage)	0.440
COL4A1	COL4A1	psi-mi:“MI:0195”(covalent binding)	0.440
COL4A1	COCH	psi-mi:“MI:0407”(direct interaction)	0.440
PLOD1	COL25A1	psi-mi:“MI:0914”(association)	0.350
TINAG	VPS26A	psi-mi:“MI:0914”(association)	0.350
MMP2	COL2A1	psi-mi:“MI:0914”(association)	0.350
COL8A1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PLOD1	PLK4	psi-mi:“MI:0914”(association)	0.350
C1QTNF1	PLOD2	psi-mi:“MI:0914”(association)	0.350
LAIR2	PLOD3	psi-mi:“MI:0914”(association)	0.350
MMP2	PLOD3	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
C1QTNF1	CALU	psi-mi:“MI:0914”(association)	0.350
FKBP9	WASL	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
	COL4A1	psi-mi:“MI:0915”(physical association)	0.000
acnA	COL4A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (47): COL4A1 (Reconstituted Complex), COL4A1 (Affinity Capture-MS), COL4A1 (Affinity Capture-MS), COL4A1 (Affinity Capture-MS), COL4A1 (Affinity Capture-MS), COL4A1 (Affinity Capture-MS), COL4A1 (Affinity Capture-MS), COL4A1 (Affinity Capture-MS), COL4A1 (Affinity Capture-Western), COL4A1 (Affinity Capture-Western), COL4A1 (Affinity Capture-RNA), COL4A1 (Two-hybrid), NID1 (Reconstituted Complex), Nid1 (Reconstituted Complex), NID2 (Reconstituted Complex)

ESM2 similar proteins: A0MSJ1, A8WR59, B8V7R6, C0HLN2, O76368, O88207, P02462, P02463, P08120, P08122, P08125, P08572, P12106, P12107, P12108, P13942, P20849, P20850, P20908, P20909, P23206, P25067, P25318, P25940, P29400, P32017, P53420, P55787, Q01955, Q03692, Q05306, Q05722, Q07643, Q0VF58, Q14031, Q14050, Q14055, Q14993, Q28083, Q28247

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

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	COL4A1	“transcriptional regulation”
TGFB1	“up-regulates quantity by expression”	COL4A1	“transcriptional regulation”
COL4A1	“up-regulates activity”	“A2/b1 integrin”	binding
COL4A1	up-regulates	ECM_synthesis
COLGALT1	“up-regulates activity”	COL4A1	glycosylation
COLGALT2	“up-regulates activity”	COL4A1	glycosylation
COL4A1	“up-regulates activity”	“A1/b1 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 41 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	9	66.7×	4e-13
Collagen chain trimerization	5	56.4×	8e-07
Collagen degradation	7	53.5×	2e-09
Assembly of collagen fibrils and other multimeric structures	5	43.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
collagen fibril organization	7	60.5×	4e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

2932 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	146
Likely pathogenic	237
Uncertain significance	1087
Likely benign	943
Benign	235

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027961	NM_001845.6(COL4A1):c.2458+1G>A	Pathogenic
1027966	NM_001845.6(COL4A1):c.4887C>G (p.Tyr1629Ter)	Pathogenic
1064614	NM_001845.6(COL4A1):c.3742+1G>A	Pathogenic
1172657	NM_001845.6(COL4A1):c.3245G>T (p.Gly1082Val)	Pathogenic
1172810	NM_001845.6(COL4A1):c.4114G>C (p.Gly1372Arg)	Pathogenic
1210101	NM_001845.6(COL4A1):c.1870G>T (p.Gly624Ter)	Pathogenic
1256082	NM_001845.6(COL4A1):c.2870G>A (p.Gly957Glu)	Pathogenic
1297056	NM_001845.6(COL4A1):c.144+1G>A	Pathogenic
1299527	NM_001845.6(COL4A1):c.3761G>A (p.Gly1254Glu)	Pathogenic
1320505	NM_001845.6(COL4A1):c.3620G>A (p.Gly1207Glu)	Pathogenic
1321996	GRCh37/hg19 13p13-q34(chr13:1-115169878)x3	Pathogenic
1322130	NM_001845.6(COL4A1):c.4150+1G>A	Pathogenic
132791	NM_001845.6(COL4A1):c.3976G>A (p.Gly1326Arg)	Pathogenic
135653	NM_001845.6(COL4A1):c.2086G>A (p.Gly696Ser)	Pathogenic
1402997	NM_001845.6(COL4A1):c.1611dup (p.Arg538fs)	Pathogenic
1411011	NC_000013.10:g.(?110839465)(110855974_?)del	Pathogenic
1442186	NM_001845.6(COL4A1):c.2930del (p.Pro977fs)	Pathogenic
1443955	NM_001845.6(COL4A1):c.3655G>T (p.Gly1219Ter)	Pathogenic
1449074	NM_001845.6(COL4A1):c.2411del (p.Pro804fs)	Pathogenic
1449300	NM_001845.6(COL4A1):c.4738G>A (p.Gly1580Ser)	Pathogenic
1450480	NM_001845.6(COL4A1):c.1890_1897+77del	Pathogenic
1452564	NM_001845.6(COL4A1):c.4408G>A (p.Gly1470Arg)	Pathogenic
1455739	NM_001845.6(COL4A1):c.2655del (p.Thr886fs)	Pathogenic
1467463	NM_001845.6(COL4A1):c.2327G>T (p.Gly776Val)	Pathogenic
1469693	NM_001845.6(COL4A1):c.1889G>A (p.Gly630Asp)	Pathogenic
1495338	NM_001845.6(COL4A1):c.452G>A (p.Gly151Asp)	Pathogenic
1514833	NM_001845.6(COL4A1):c.2414G>A (p.Gly805Glu)	Pathogenic
1527881	NM_001845.6(COL4A1):c.2458+1G>C	Pathogenic
161440	NM_001845.6(COL4A1):c.2085del (p.Gly696fs)	Pathogenic
161441	NM_001845.6(COL4A1):c.2194-1G>A	Pathogenic

SpliceAI

6221 predictions. Top by Δscore:

Variant	Effect	Δscore
13:110152332:A:AC	donor_gain	1.0000
13:110152333:C:CC	donor_gain	1.0000
13:110152502:GTGTG:G	acceptor_gain	1.0000
13:110152503:TGTG:T	acceptor_gain	1.0000
13:110152504:GTG:G	acceptor_gain	1.0000
13:110152505:TG:T	acceptor_gain	1.0000
13:110152505:TGCTG:T	acceptor_loss	1.0000
13:110152507:C:CC	acceptor_gain	1.0000
13:110152507:CTGCA:C	acceptor_loss	1.0000
13:110155393:CACAC:C	acceptor_gain	1.0000
13:110155395:CAC:C	acceptor_gain	1.0000
13:110155397:CCT:C	acceptor_loss	1.0000
13:110155398:C:CA	acceptor_loss	1.0000
13:110155398:C:CC	acceptor_gain	1.0000
13:110155399:T:C	acceptor_loss	1.0000
13:110161191:CCTA:C	donor_gain	1.0000
13:110161365:CGTGC:C	acceptor_gain	1.0000
13:110161370:C:CC	acceptor_gain	1.0000
13:110161370:C:G	acceptor_loss	1.0000
13:110161371:T:C	acceptor_loss	1.0000
13:110164856:TCTCA:T	donor_loss	1.0000
13:110164857:CTCAC:C	donor_loss	1.0000
13:110164858:TCA:T	donor_loss	1.0000
13:110164859:CA:C	donor_loss	1.0000
13:110164860:A:C	donor_loss	1.0000
13:110164861:CCTT:C	donor_loss	1.0000
13:110164990:CCTG:C	acceptor_loss	1.0000
13:110164991:C:CC	acceptor_gain	1.0000
13:110164991:CTGT:C	acceptor_loss	1.0000
13:110164992:T:A	acceptor_loss	1.0000

AlphaMissense

10510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:110150378:A:C	C1665W	1.000
13:110150379:C:G	C1665S	1.000
13:110150379:C:T	C1665Y	1.000
13:110150380:A:G	C1665R	1.000
13:110150380:A:T	C1665S	1.000
13:110150387:G:C	C1662W	1.000
13:110150388:C:A	C1662F	1.000
13:110150388:C:G	C1662S	1.000
13:110150388:C:T	C1662Y	1.000
13:110150389:A:G	C1662R	1.000
13:110150389:A:T	C1662S	1.000
13:110150393:G:C	S1660R	1.000
13:110150393:G:T	S1660R	1.000
13:110150395:T:G	S1660R	1.000
13:110152364:A:G	L1633P	1.000
13:110152366:C:A	W1632C	1.000
13:110152366:C:G	W1632C	1.000
13:110152368:A:G	W1632R	1.000
13:110152368:A:T	W1632R	1.000
13:110152369:A:C	F1631L	1.000
13:110152369:A:T	F1631L	1.000
13:110152371:A:G	F1631L	1.000
13:110152372:G:C	S1630R	1.000
13:110152372:G:T	S1630R	1.000
13:110152374:T:G	S1630R	1.000
13:110152396:G:C	C1622W	1.000
13:110152397:C:A	C1622F	1.000
13:110152397:C:G	C1622S	1.000
13:110152397:C:T	C1622Y	1.000
13:110152398:A:G	C1622R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000454 (13:110183752 C>T), RS1000010134 (13:110219886 A>G), RS1000037016 (13:110256315 G>A), RS1000060894 (13:110245123 T>C), RS1000063473 (13:110265457 G>A), RS1000069346 (13:110225716 C>A), RS1000103536 (13:110298745 G>C), RS1000110887 (13:110285828 C>A), RS1000113908 (13:110261757 G>T), RS1000115343 (13:110209412 G>A), RS1000150998 (13:110170924 C>A,T), RS1000163418 (13:110222628 C>G), RS1000186608 (13:110276654 C>A), RS1000212083 (13:110220364 G>A), RS1000232875 (13:110289166 T>G)

Disease associations

OMIM: gene MIM:120130 | disease phenotypes: MIM:175780, MIM:607595, MIM:180000, MIM:611773, MIM:618564, MIM:614519, MIM:610805, MIM:217990, MIM:269160, MIM:107250, MIM:148300, MIM:604229, MIM:614483, MIM:141200, MIM:607086, MIM:161800

GenCC curated gene-disease

Disease	Classification	Inheritance
brain small vessel disease 1 with or without ocular anomalies	Strong	Autosomal dominant
autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome	Strong	Autosomal dominant
microangiopathy and leukoencephalopathy, pontine, autosomal dominant	Moderate	Autosomal dominant
pontine autosomal dominant microangiopathy with leukoencephalopathy	Supportive	Autosomal dominant
retinal arterial tortuosity	Supportive	Autosomal dominant
muscular dystrophy-dystroglycanopathy, type A	Supportive	Autosomal recessive
familial porencephaly	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
COL4A1-related disorder	Definitive	AD

Mondo (32): brain small vessel disease 1 with or without ocular anomalies (MONDO:0008289), retinal arterial tortuosity (MONDO:0008373), autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome (MONDO:0012726), microangiopathy and leukoencephalopathy, pontine, autosomal dominant (MONDO:0032814), hemorrhage, intracerebral, susceptibility to (MONDO:0100533), COL4A1-related disorder (MONDO:0800461), congenital anomaly of kidney and urinary tract (MONDO:0019719), corpus callosum, agenesis of (MONDO:0009022), colpocephaly (MONDO:0022236), porencephaly (MONDO:0017410), cerebral palsy (MONDO:0006497), vascular dementia (MONDO:0004648), factor VII deficiency (MONDO:0002244), factor X deficiency (MONDO:0002247), primary membranoproliferative glomerulonephritis (MONDO:0018904)

Orphanet (19): Porencephaly (Orphanet:2940), COL4A1/2-related familial vascular leukoencephalopathy (Orphanet:36383), Pontine autosomal dominant microangiopathy with leukoencephalopathy (Orphanet:477749), HANAC syndrome (Orphanet:73229), Familial isolated retinal arteriolar tortuosity (Orphanet:75326), Familial porencephaly (Orphanet:99810), Renal or urinary tract malformation (Orphanet:93545), Isolated corpus callosum agenesis (Orphanet:200), COL4A1 or COL4A2-related cerebral small vessel disease (Orphanet:477759), Primary membranoproliferative glomerulonephritis (Orphanet:54370), Schizencephaly (Orphanet:799), Anterior segment developmental anomaly (Orphanet:88632), Peters anomaly (Orphanet:708), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), Congenital myopathy with excess of thin filaments (Orphanet:98904)

HPO phenotypes

114 total (30 of 114 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000083	Renal insufficiency
HP:0000107	Renal cyst
HP:0000175	Cleft palate
HP:0000176	Submucous cleft hard palate
HP:0000193	Bifid uvula
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000501	Glaucoma
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000528	Anophthalmia
HP:0000540	Hypermetropia
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000572	Visual loss
HP:0000573	Retinal hemorrhage
HP:0000577	Exotropia
HP:0000587	Abnormal optic nerve morphology
HP:0000612	Iris coloboma
HP:0000613	Photophobia

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST000370_1	Arterial stiffness	5.000000e-08
GCST000998_11	Coronary heart disease	4.000000e-09
GCST001762_472	Obesity-related traits	7.000000e-07
GCST001762_832	Obesity-related traits	5.000000e-08
GCST002289_12	Coronary artery disease	2.000000e-06
GCST002498_1	Age-related nuclear cataracts	2.000000e-06
GCST002866_2	Behavioral disturbance or psychiatric symptoms and prion disease	5.000000e-06
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
GCST004625_142	Monocyte count	1.000000e-09
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_53	Coronary artery disease	4.000000e-17
GCST005194_54	Coronary artery disease	4.000000e-17
GCST005196_1	Coronary artery disease	2.000000e-10
GCST005196_75	Coronary artery disease	3.000000e-15
GCST006412_84	Intraocular pressure	2.000000e-09
GCST007248_2	Stroke	4.000000e-08
GCST007269_322	Pulse pressure	2.000000e-10
GCST007644_1	Estimated glomerular filtration rate after 1 year in renal transplantation (donor effect)	8.000000e-07
GCST008159_62	Waist-to-hip ratio adjusted for BMI	5.000000e-06
GCST008474_16	Peripheral artery disease	8.000000e-10
GCST008876_13	Non-lobar intracerebral hemorrhage (MTAG)	2.000000e-07
GCST009207_13	Lateral ventricle volume	4.000000e-06
GCST009391_1511	Metabolite levels	4.000000e-06
GCST009646_2	Diastolic blood pressure response to thiazide and thiazide-like diuretics in hypertension	1.000000e-08
GCST009723_3	Vertical cup-disc ratio (adjusted for vertical disc diameter)	5.000000e-14
GCST009724_53	Vertical cup-disc ratio (multi-trait analysis)	8.000000e-11

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004517	arterial stiffness measurement
EFO:0004626	IGFBP-3 measurement
EFO:0004338	body weight
EFO:0005091	monocyte count
EFO:0004695	intraocular pressure measurement
EFO:0005763	pulse pressure measurement
EFO:0005199	renal transplant outcome measurement
EFO:0007892	donor genotype effect measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0010178	non-lobar intracerebral hemorrhage
EFO:0008487	lateral ventricle volume measurement
EFO:0010417	triacylglycerol 52:5 measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004587	lymphocyte count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (23)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
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
D005168	Factor VII Deficiency	C15.378.100.100.310; C15.378.100.141.310; C15.378.463.310; C16.320.099.310
D005171	Factor X Deficiency	C15.378.100.100.320; C15.378.100.141.320; C15.378.463.320; C16.320.099.320
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007640	Keratoconus	C11.204.627
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500
D008659	Metabolic Diseases	C18.452
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065708	Porencephaly	C05.660.207.620.500; C10.500.507.500.625; C16.131.621.207.620.500; C16.131.666.507.500.625
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
D051437	Renal Insufficiency	C12.050.351.968.419.780; C12.200.777.419.780; C12.950.419.780
D065707	Schizencephaly	C10.500.507.500.750; C16.131.666.507.500.750
D058494	Walker-Warburg Syndrome	C10.500.507.450.499.249.500; C11.270.881; C16.131.666.507.450.499.249.500; C16.320.577.750
C579880	Actin-Accumulation Myopathy (supp.)
C567088	Angiopathy, Hereditary, With Nephropathy, Aneurysms, And Muscle Cramps (supp.)
C566906	Cakut (supp.)
C535973	Colpocephaly (supp.)
C531642	Familial vascular leukoencephalopathy (supp.)
C562476	Hematuria, Benign Familial (supp.)
C580202	Intranuclear Rod Myopathy (supp.)
C537884	Peters anomaly (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

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, decreases methylation, increases expression, affects expression	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	4
Cyclosporine	decreases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Cadmium	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Copper	affects binding, decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	affects methylation, decreases methylation	2
Particulate Matter	affects expression, increases reaction, decreases expression	2
peracetylated N-azidoacetylmannosamine	decreases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	decreases expression	1
apocarotenal	decreases expression	1
deoxynivalenol	decreases expression	1
arsenite	affects binding, decreases reaction	1
schizandrin B	affects reaction, decreases reaction, increases expression, decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
cupric oxide	decreases expression	1
hydroquinone	affects cotreatment, decreases expression, increases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1NU	Abcam HeLa COL4A1 KO	Cancer cell line	Female
CVCL_E0AJ	Ubigene HeLa COL4A1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

301 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
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	PHASE3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	PHASE3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	PHASE3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	PHASE3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	PHASE3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	PHASE3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	PHASE3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years
NCT01929434	PHASE3	COMPLETED	Efficacy of Stem Cell Transplantation Compared to Rehabilitation Treatment of Patients With Cerebral Paralysis
NCT02002884	PHASE3	COMPLETED	Dose-response Study of Efficacy and Safety of Botulinum Toxin Type A to Treat Spasticity of the Arm(s) or of Arm(s) and Leg(s) in Cerebral Palsy
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02839785	PHASE3	TERMINATED	Analgesia and Physiotherapy in Children With Cerebral Palsy (ANTALKINECP)
NCT03110341	PHASE3	UNKNOWN	Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
NCT03302871	PHASE3	COMPLETED	Integrated Management Enhances Functional Gains in Children With Cerebral Palsy Treated by BoNT-A
NCT03306212	PHASE3	COMPLETED	Efficacy of Intermittent Serial Casting on Spastic Wrist Flexion Deformity