COL4A4

Summary

COL4A4 (collagen type IV alpha 4 chain, HGNC:2206) is a protein-coding gene on chromosome 2q36.3, encoding Collagen alpha-4(IV) chain (P53420). 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. This particular collagen IV subunit, however, is only found in a subset of basement membranes. 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. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3’ UTR.

Source: NCBI Gene 1286 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Alport syndrome (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 3,774 total — 257 pathogenic, 517 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• MANE Select transcript: NM_000092

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2206
Approved symbol	COL4A4
Name	collagen type IV alpha 4 chain
Location	2q36.3
Locus type	gene with protein product
Status	Approved
Aliases	CA44
Ensembl gene	ENSG00000081052
Ensembl biotype	protein_coding
OMIM	120131
Entrez	1286

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000396625, ENST00000643379, ENST00000682098, ENST00000682248, ENST00000682548, ENST00000683508, ENST00000684257, ENST00000684524

RefSeq mRNA: 1 — MANE Select: NM_000092 NM_000092

CCDS: CCDS42828

Canonical transcript exons

ENST00000396625 — 48 exons

Exon	Start	End
ENSE00001071074	227059405	227059623
ENSE00001124594	227022048	227022173
ENSE00001124612	227002714	227007588
ENSE00001135763	227012181	227012297
ENSE00001135841	227008018	227008304
ENSE00001135926	227094125	227094289
ENSE00001135929	227098694	227098798
ENSE00001305015	227057439	227057600
ENSE00001311859	227010313	227010501
ENSE00001313262	227032148	227032276
ENSE00001315992	227027902	227028009
ENSE00001321359	227031945	227032055
ENSE00001326349	227055945	227056115
ENSE00001328587	227030443	227030598
ENSE00001331272	227077894	227078077
ENSE00001377510	227050977	227051158
ENSE00001385501	227042148	227042255
ENSE00001387144	227054594	227054737
ENSE00001387733	227043077	227043184
ENSE00001400869	227033410	227033481
ENSE00001403233	227121014	227121148
ENSE00001404531	227052305	227052412
ENSE00001414504	227060136	227060243
ENSE00001422171	227080443	227080549
ENSE00001431479	227088653	227088816
ENSE00001434411	227118645	227118761
ENSE00001461298	227047475	227047549
ENSE00001461299	227050068	227050131
ENSE00001461300	227062530	227062598
ENSE00001461302	227082115	227082187
ENSE00001461305	227089868	227089957
ENSE00001461306	227099620	227099689
ENSE00001461307	227101504	227101557
ENSE00001461308	227101865	227101909
ENSE00001461309	227102789	227102848
ENSE00001461310	227103144	227103197
ENSE00001461311	227103972	227104052
ENSE00001461312	227108581	227108622
ENSE00001461313	227108833	227108868
ENSE00001461314	227109224	227109286
ENSE00001461316	227111678	227111713
ENSE00001461317	227114628	227114696
ENSE00001461319	227119895	227119939
ENSE00001461320	227140161	227140238
ENSE00001461321	227144516	227144558
ENSE00001461322	227147413	227147584
ENSE00001831933	227164007	227164205
ENSE00002511083	227025802	227025810

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 87.51.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8577 / max 134.8880, expressed in 516 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34338	1.8190	428
34339	0.7027	294
34341	0.2233	104
34337	0.0900	34
34340	0.0227	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	87.51	gold quality
metanephros cortex	UBERON:0010533	86.40	gold quality
pigmented layer of retina	UBERON:0001782	81.91	gold quality
cauda epididymis	UBERON:0004360	81.77	gold quality
right coronary artery	UBERON:0001625	80.26	gold quality
coronary artery	UBERON:0001621	79.80	gold quality
left coronary artery	UBERON:0001626	79.70	gold quality
caput epididymis	UBERON:0004358	79.48	gold quality
visceral pleura	UBERON:0002401	79.45	gold quality
ascending aorta	UBERON:0001496	79.36	gold quality
thoracic aorta	UBERON:0001515	79.34	gold quality
kidney	UBERON:0002113	79.20	gold quality
right atrium auricular region	UBERON:0006631	79.15	gold quality
adult mammalian kidney	UBERON:0000082	78.95	gold quality
left lobe of thyroid gland	UBERON:0001120	78.94	gold quality
descending thoracic aorta	UBERON:0002345	78.92	gold quality
pituitary gland	UBERON:0000007	78.86	gold quality
cortex of kidney	UBERON:0001225	78.85	gold quality
thyroid gland	UBERON:0002046	78.77	gold quality
cardiac atrium	UBERON:0002081	78.70	gold quality
biceps brachii	UBERON:0001507	78.08	silver quality
mucosa of stomach	UBERON:0001199	77.81	gold quality
metanephros	UBERON:0000081	77.73	gold quality
right lobe of thyroid gland	UBERON:0001119	77.55	gold quality
seminal vesicle	UBERON:0000998	77.49	gold quality
adenohypophysis	UBERON:0002196	77.38	gold quality
adrenal cortex	UBERON:0001235	76.69	gold quality
left adrenal gland	UBERON:0001234	76.68	gold quality
right adrenal gland cortex	UBERON:0035827	76.53	gold quality
left adrenal gland cortex	UBERON:0035825	76.29	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): LMX1B

miRNA regulators (miRDB)

170 targeting COL4A4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 40)

• COL4A4 mutation: from familial hematuria to autosomal-dominant or recessive Alport syndrome. (PMID:12028435)
• No collagen alpha3(IV) or alpha4(IV) in lens capsules of 54-day human embryos, while collagen alpha3(IV) and alpha4(IV) were detected in adult humans. (PMID:12225806)
• Six of seven (86%) individuals with autosomal recessive Alport syndrome who had 3 novel COL4A4 mutations in the compound heterozygous or homozygous forms developed renal failure in adulthood, as well as hearing loss and ocular abnormalities. (PMID:12325029)
• Two stop codons (R1377X and 2788/91delG) and a glycine substitution (G960R) resulted in hematuria. S969X mutation. (PMID:12631110)
• COL4A4 gene is associted with Alport’s syndrome in which males and females are severely affected. (PMID:12768082)
• In kidney, when expressed onto Col4a3(-/-) background, human alpha3(IV) chain restored expression of and co-assembled with mouse alpha4 and alpha5(IV) chains at sites where human alpha3(IV) was expressed. All three chains required for network assembly. (PMID:14507670)
• Mutations in COL4A3 and COL4A4 genes produce alteration to glomerular basement membrane(GBM). Phenotype may range from thinned GBM ro GBM thickening, lamellation and splitting. Review. (PMID:15280517)
• 40% of families with TBMN have hematuria that segregates with the corresponding locus ( COL4A3/COL4A4 ), and identical mutations occur in both conditions. (PMID:15880327)
• novel mutations identified during routine molecular diagnostics for Alport syndrome (PMID:15954103)
• Persistent familial hematuria in children often occurs at the COLA4A locus for thin membrane nephropathy. (PMID:16235097)
• The molecular analysis demonstrated that the probands were genetic compounds for two different mutations in the COL4A4 gene pinpointing to the correct diagnosis of autosomal recessive ATS. (PMID:16338941)
• Possibly mutated in Alport syndrome (review) (PMID:16895672)
• A clinical evaluation of probands and their relatives of the five families carrying mutations in either the COL4A3 or the COL4A4 gene was carried out to underline the natural history of the autosomal recessive ATS. (PMID:16970251)
• Polymorphisms in thus genes is particularly important to enable diagnostic laboratories to distinguish mutations from uncommon normal variants. (PMID:17216251)
• 16 novel mutations identified in COL4A3, COL4A4 & COL4A5 genes in Slovenian families with Alport syndrome & benign familial hematuria (BFH); 4 heterozygous mutations in COL4A4 (2 splice site, 1 in-frame deletion & 1 missense) identified in BFH (PMID:17396119)
• COL4A3/COL4A4 mutations predispose some patients to FSGS and chronic renal failure. (PMID:17942953)
• our data show many patients with collagen IV mutations may develop focal & segmental glomerulosclerosis, on top of thin basement membrane nephropathy & microscopic hematuria, which often progresses to chronic renal failure or end-stage renal disease (PMID:18661361)
• analysis of noncollagenous sites encoding specific interactions and quaternary assembly of alpha 3 alpha 4 alpha 5(IV) collagen (PMID:18930919)
• On the basis of linked-function analysis, we demonstrated that collagen binding domain of MMP2 tuned the cleavage of collagen IV by MMP9, presumably by inducing a ligand-linked structural change on the type IV collagen. (PMID:19109975)
• It is difficult to make a differential diagnosis with a benign familial haematuria due to heterozygous mutations of COL4A4 and COL4A3, especially in young patients, and with a X-linked form of Alport syndrome in families where only females are affected. (PMID:19129241)
• association of heterozygous COL4A3/COL4A4 mutations with familial microscopic haematuria, thin basement membrane nephropathy and the late development of familial proteinuria, CRF, and ESRD, due to FSGS (PMID:19357112)
• Novel variants in the COL4A4 gene in Korean patients with thin basement membrane nephropathy. (PMID:19675380)
• This is the first mutational screening of COL4A3 and COL4A4 genes in keratoconus patients to establish the status of these genes and compare them to a control population. (PMID:20029656)
• The absence of pathogenic mutations in COL4A4 gene in our large number of unrelated keratoconus patients indicates that other genetic factors are involved in the development of this disorder (PMID:20664914)
• Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina. (PMID:22723992)
• 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)
• 9 mutation in COL4A4 associated with autosomal dominant Alport syndrome. (PMID:24033287)
• Twenty mutation pairs (50%) affected COL4A3 and 20 pairs affected COL4A4 in Alport syndrome. (PMID:24052634)
• COL4A4 related nephropathy caused by novel mutation in a large consanguineous Saudi family. (PMID:24398087)
• We could hypothesize that mutations in COL4A3 and COL4A4 genes are not involved in keratoconus risk in Greek population. (PMID:25083577)
• We found that 7 out of 70 families (10%) with familial focal segmental glomerulosclerosis in our cohort have rare variants in COL4A3 and COL4A4. (PMID:25229338)
• New COL4A4 mutations among Portuguese patients with collagen IV-related nephropathies were identified in 8 unrelated families. (PMID:25307543)
• COL4A4 missense variants [c.G2636A (p.Gly879Glu) and c.C4715T (p.Pro1572Leu)] in family 1. COL4A4 c.G2636A, a novel variant, co-segregated with renal disease among maternal relatives. (PMID:25381091)
• we identified seven families with associated mutations in COL4A3 and COL4A4 genes and four families with associated mutations in COL4A4 and COL4A5. We did not find kindreds with digenic inheritance attributable to mutations in COL4A3 and COL4A5 (PMID:25575550)
• COL4A4 rs2229813 AA and GA+AA genotypes as well as the A allele play roles as risk factors for developing Keratoconus in our population. (PMID:25651396)
• Tetrastatin, the NC1 alpha 4 collagen IV domain level increases in pulmonary tumor extracts. (PMID:25935259)
• we describe a novel splicing mutation in COL4A4 that results in TBMN. This analysis increases our understanding of TBMN phenotype-genotype correlations, which should facilitate more accurate diagnosis and prenatal diagnosis of TBMN. (PMID:26833262)
• These findings indicate that the heterozygous mutations in COL4A3 or COL4A4 may cause ESRD on their own, although secondary factors, such as environmental factors or unknown genetic changes, might also contribute to the phenotype of kidney disease in patients with ADAS. (PMID:27281700)
• This finding broadens mutation spectrum of the COL4A4 gene and extends the phenotypic spectrum of collagen IV nephropathies. (PMID:27469977)
• Alport syndrome is the result of mutations in any of three type IV collagen genes, COL4A3, COL4A4, or COL4A5. Because the three collagen chains form heterotrimers, there is an absence of all three proteins in the basement membranes where they are expressed. (Review) (PMID:27576055)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	col4a4	ENSDARG00000002831
mus_musculus	Col4a4	ENSMUSG00000067158
rattus_norvegicus	Col4a4	ENSRNOG00000014851
drosophila_melanogaster	vkg	FBGN0016075
caenorhabditis_elegans		WBGENE00001263

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL17A1 (ENSG00000065618), COL5A3 (ENSG00000080573), 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), 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-4(IV) chain — P53420 (reviewed: P53420)

All UniProt accessions (5): P53420, A0A2R8Y548, A0A804HI71, A0A804HI86, A0A804HLF6

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.

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. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite protomer, respectively. Associates with LAMB2 at the neuromuscular junction and in GBM.

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

Tissue specificity. Expressed in Bruch’s membrane, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, inner limiting membrane and around the blood vessels of the retina (at protein level). Alpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. PubMed:8083201 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but PubMed:7523402 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. Highest levels of expression of alpha 4 type IV collagen are detected in kidney, calvaria, neuroretina and cardiac muscle. Lower levels of expression are observed in brain, lung and thymus, and no expression is detected in choroid plexus, liver, adrenal, pancreas, ileum or skin.

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.

Disease relevance. Alport syndrome 2, autosomal recessive (ATS2) [MIM:203780] A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness. The disease is caused by variants affecting the gene represented in this entry. Hematuria, benign familial, 1 (BFH1) [MIM:141200] An autosomal dominant condition characterized by non-progressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane. The disease is caused by 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_000083* (*=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 (97 total): compositionally biased region 21, sequence variant 21, strand 18, short sequence motif 8, region of interest 7, disulfide bond 6, helix 6, glycosylation site 2, sequence conflict 2, turn 2, signal peptide 1, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6WKU	X-RAY DIFFRACTION	1.76
5NB1	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53420-F1	49.03	0.08

Functional residue map

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

Catalytic / active sites (1): 1206–1207 (cleavage; by collagenase)

Disulfide bonds (6): 1480–1569, 1513–1566, 1525–1531, 1588–1686, 1622–1683, 1634–1641

Glycosylation sites (2): 142, 669

Function

Pathways and Gene Ontology

Reactome pathways

14 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-419037	NCAM1 interactions
R-HSA-8948216	Collagen chain trimerization
R-HSA-9638630	Attachment of bacteria to epithelial cells

MSigDB gene sets: 251 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, MYOGENIN_Q6, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, MODULE_571, FISCHER_G1_S_CELL_CYCLE, GOCC_COLLAGEN_TRIMER, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, REACTOME_NCAM_SIGNALING_FOR_NEURITE_OUT_GROWTH, RIZKI_TUMOR_INVASIVENESS_3D_DN, LHX3_01, TTGGGAG_MIR150, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, CEBP_Q2

GO Biological Process (2): collagen fibril organization (GO:0030199), glomerular basement membrane development (GO:0032836)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), extracellular matrix structural constituent conferring tensile strength (GO:0030020), molecular adaptor activity (GO:0060090)

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-8 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
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 organization	2
extracellular matrix	2
glomerulus development	1
anatomical structure development	1
structural molecule activity	1
extracellular matrix structural constituent	1
molecular_function	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

1224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL4A4	IGBP1	P78318	858
COL4A4	NPHS1	O60500	768
COL4A4	NPHS2	Q9NP85	763
COL4A4	LMX1B	O60663	704
COL4A4	MYH9	P35579	664
COL4A4	CD151	P48509	604
COL4A4	NID1	P14543	588
COL4A4	COL4A3	Q01955	535
COL4A4	RHBDD1	Q8TEB9	526
COL4A4	VSX1	Q9NZR4	507
COL4A4	INF2	Q27J81	476
COL4A4	LMX1A	Q8TE12	470
COL4A4	NKX2-2	O95096	470
COL4A4	COL4A5	P29400	469
COL4A4	LHX1	P48742	444

IntAct

10 interactions, top by confidence:

A	B	Type	Score
KLK6	COL4A4	psi-mi:“MI:0570”(protein cleavage)	0.440
COL4A4	HNRNPM	psi-mi:“MI:0915”(physical association)	0.400
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
FGD6	COL4A4	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
LAIR2	PLOD3	psi-mi:“MI:0914”(association)	0.350
LAIR2	AGRN	psi-mi:“MI:0914”(association)	0.350
PLOD1	PLOD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): COL4A4 (Protein-RNA), COL4A4 (Proximity Label-MS), COL4A4 (Affinity Capture-MS), COL4A4 (Affinity Capture-MS), COL4A4 (Affinity Capture-MS), COL4A4 (Proximity Label-MS), COL4A4 (Affinity Capture-MS), ACAA2 (Cross-Linking-MS (XL-MS)), COL4A4 (Affinity Capture-MS)

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
COL4A4	“up-regulates activity”	“A2/b1 integrin”	binding
COL4A4	up-regulates	ECM_synthesis
PXDN	“up-regulates quantity by stabilization”	COL4A4	“catalytic activity”
COL4A4	“up-regulates activity”	“A1/b1 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

3774 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	257
Likely pathogenic	517
Uncertain significance	966
Likely benign	1369
Benign	183

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1036012	NM_000092.5(COL4A4):c.870G>A (p.Lys290=)	Pathogenic
1068523	NM_000092.5(COL4A4):c.118G>T (p.Gly40Ter)	Pathogenic
1069400	NM_000092.5(COL4A4):c.3319_3358del (p.Leu1107fs)	Pathogenic
1070032	NM_000092.5(COL4A4):c.1768G>T (p.Gly590Ter)	Pathogenic
1070585	NM_000092.5(COL4A4):c.4200dup (p.Gly1401fs)	Pathogenic
1070939	NM_000092.5(COL4A4):c.2219_2220del (p.Pro740fs)	Pathogenic
1070978	NM_000092.5(COL4A4):c.2906C>A (p.Ser969Ter)	Pathogenic
1071074	NM_000092.5(COL4A4):c.1696+1del	Pathogenic
1073049	NM_000092.5(COL4A4):c.4962_4969dup (p.Ala1657delinsGlyTer)	Pathogenic
1073470	NM_000092.5(COL4A4):c.4444del (p.Leu1482fs)	Pathogenic
1073781	NM_000092.5(COL4A4):c.4449_4450dup (p.Met1484fs)	Pathogenic
1073782	NM_000092.5(COL4A4):c.2842G>T (p.Gly948Ter)	Pathogenic
1073919	NM_000092.5(COL4A4):c.156C>A (p.Cys52Ter)	Pathogenic
1075869	NM_000092.5(COL4A4):c.1862del (p.Pro621fs)	Pathogenic
1076015	NM_000092.5(COL4A4):c.794_804del (p.Asp264_Phe265insTer)	Pathogenic
1284919	NM_000092.5(COL4A4):c.2833G>T (p.Gly945Ter)	Pathogenic
1298378	NM_000092.5(COL4A4):c.2860+2T>G	Pathogenic
1342006	NM_000092.5(COL4A4):c.4720C>T (p.Gln1574Ter)	Pathogenic
1344700	NM_000092.5(COL4A4):c.2383G>A (p.Gly795Arg)	Pathogenic
1344701	NM_000092.5(COL4A4):c.4503dup (p.Ala1502fs)	Pathogenic
1344702	NM_000092.5(COL4A4):c.1697-1G>C	Pathogenic
1350377	NM_000092.5(COL4A4):c.4787G>A (p.Trp1596Ter)	Pathogenic
1356715	NM_000092.5(COL4A4):c.4849_4850del (p.Met1617fs)	Pathogenic
1359803	NM_000092.5(COL4A4):c.2531_2537del (p.Tyr844fs)	Pathogenic
1366631	NC_000002.11:g.(?227872031)(227985874_?)del	Pathogenic
1374552	NM_000092.5(COL4A4):c.4473_4474dup (p.Ser1492fs)	Pathogenic
1382507	NM_000092.5(COL4A4):c.2196del (p.Phe732fs)	Pathogenic
1385943	NM_000092.5(COL4A4):c.1143_1144del (p.Asp383fs)	Pathogenic
1386713	NM_000092.5(COL4A4):c.1247del (p.Pro416fs)	Pathogenic
1399009	NM_000092.5(COL4A4):c.105T>G (p.Tyr35Ter)	Pathogenic

SpliceAI

6201 predictions. Top by Δscore:

Variant	Effect	Δscore
2:227010273:A:AC	donor_gain	1.0000
2:227010274:C:CC	donor_gain	1.0000
2:227025861:G:C	acceptor_gain	1.0000
2:227025880:T:C	acceptor_gain	1.0000
2:227027896:GCTCA:G	donor_loss	1.0000
2:227027897:CTCAC:C	donor_loss	1.0000
2:227027898:TCACC:T	donor_loss	1.0000
2:227027899:CACCC:C	donor_loss	1.0000
2:227027900:A:AC	donor_gain	1.0000
2:227027900:AC:A	donor_gain	1.0000
2:227027900:ACCCG:A	donor_loss	1.0000
2:227027901:C:A	donor_loss	1.0000
2:227027901:C:CC	donor_gain	1.0000
2:227027901:CC:C	donor_gain	1.0000
2:227027927:C:CA	donor_gain	1.0000
2:227028009:CCT:C	acceptor_gain	1.0000
2:227028010:C:CC	acceptor_gain	1.0000
2:227028011:T:C	acceptor_gain	1.0000
2:227028011:T:TC	acceptor_gain	1.0000
2:227030438:CATA:C	donor_loss	1.0000
2:227030441:A:AC	donor_gain	1.0000
2:227030441:A:C	donor_loss	1.0000
2:227030442:C:CC	donor_gain	1.0000
2:227030442:C:CT	donor_loss	1.0000
2:227030442:CCTTT:C	donor_gain	1.0000
2:227030468:T:TA	donor_gain	1.0000
2:227030594:TGCTC:T	acceptor_gain	1.0000
2:227030596:CTC:C	acceptor_gain	1.0000
2:227030598:CCT:C	acceptor_loss	1.0000
2:227030599:C:CC	acceptor_gain	1.0000

AlphaMissense

10580 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:227010359:A:C	S1492R	0.998
2:227010359:A:T	S1492R	0.998
2:227010361:T:G	S1492R	0.998
2:227007535:G:C	S1621R	0.997
2:227007535:G:T	S1621R	0.997
2:227007537:T:G	S1621R	0.997
2:227008135:G:C	S1564R	0.997
2:227008135:G:T	S1564R	0.997
2:227008137:T:G	S1564R	0.997
2:227007350:C:G	C1683S	0.996
2:227007351:A:T	C1683S	0.996
2:227007532:G:C	C1622W	0.996
2:227007497:C:G	C1634S	0.995
2:227007498:A:T	C1634S	0.995
2:227007445:C:A	W1651C	0.994
2:227007445:C:G	W1651C	0.994
2:227007533:C:G	C1622S	0.994
2:227007533:C:T	C1622Y	0.994
2:227007534:A:T	C1622S	0.994
2:227008130:C:G	C1566S	0.994
2:227008131:A:T	C1566S	0.994
2:227008201:C:A	W1542C	0.994
2:227008201:C:G	W1542C	0.994
2:227008288:G:C	C1513W	0.994
2:227007349:G:C	C1683W	0.993
2:227007351:A:G	C1683R	0.993
2:227007443:A:G	L1652P	0.993
2:227007447:A:G	W1651R	0.993
2:227007447:A:T	W1651R	0.993
2:227007534:A:G	C1622R	0.993

dbSNP variants (sampled 300 via entrez): RS1000026260 (2:227065328 G>C), RS1000029305 (2:227038752 A>G), RS1000038316 (2:227071486 G>A,C), RS1000058225 (2:227155486 G>C), RS1000067030 (2:226981305 T>G), RS1000088961 (2:227154972 T>C), RS1000093117 (2:227056206 T>C), RS1000094354 (2:227112850 T>G), RS1000106924 (2:227030004 T>C), RS1000109668 (2:227117803 A>C,G), RS1000121696 (2:226988117 A>T), RS1000123870 (2:227126177 A>G), RS1000137686 (2:227142600 CA>C,CAA), RS1000139419 (2:227030413 A>G,T), RS1000176849 (2:227055925 A>G)

Disease associations

OMIM: gene MIM:120131 | disease phenotypes: MIM:141200, MIM:203780, MIM:301050, MIM:104200, MIM:156000, MIM:173900, MIM:614483, MIM:160700, MIM:276900, MIM:615432

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive Alport syndrome	Definitive	Autosomal recessive
Alport syndrome	Definitive	Semidominant
hematuria, benign familial, 1	Strong	Autosomal dominant
autosomal dominant Alport syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Alport syndrome	Definitive	SD

Mondo (24): hematuria, benign familial, 1 (MONDO:0007709), autosomal recessive Alport syndrome (MONDO:0008762), Alport syndrome (MONDO:0018965), hematuria, benign familial (MONDO:0957317), autosomal dominant Alport syndrome (MONDO:0007086), Meniere disease (MONDO:0007972), hearing loss disorder (MONDO:0005365), kidney disorder (MONDO:0005240), focal segmental glomerulosclerosis (MONDO:0100313), polycystic kidney disease (MONDO:0020642), X-linked Alport syndrome (MONDO:0010520), brain small vessel disease 2A, autosomal dominant (MONDO:0013773), myopia (MONDO:0001384), proteinuria (MONDO:0003634), hypertensive disorder (MONDO:0005044)

Orphanet (10): Alport syndrome (Orphanet:63), Autosomal recessive Alport syndrome (Orphanet:88919), Autosomal dominant Alport syndrome (Orphanet:88918), X-linked Alport syndrome (Orphanet:88917), Porencephaly (Orphanet:2940), Familial porencephaly (Orphanet:99810), Usher syndrome (Orphanet:886), Atypical hemolytic uremic syndrome (Orphanet:2134), NON RARE IN EUROPE: Benign familial hematuria (Orphanet:97562), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000123	Nephritis
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000545	Myopia
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000829	Hypoparathyroidism
HP:0001142	Lenticonus
HP:0001417	X-linked inheritance
HP:0001423	X-linked dominant inheritance
HP:0001873	Thrombocytopenia
HP:0002907	Microscopic hematuria
HP:0003676	Progressive
HP:0003680	Nonprogressive
HP:0003774	Stage 5 chronic kidney disease
HP:0004722	Thickened glomerular basement membrane
HP:0006756	Diffuse leiomyomatosis
HP:0008064	Ichthyosis
HP:0011501	Anterior lenticonus
HP:0012577	Thin glomerular basement membrane
HP:0030034	Glomerular basement membrane lamellation
HP:0200020	Corneal erosion
HP:6001026	Reduced epidermal collagen IV alpha 5 chain staining

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001538_19	Immune reponse to smallpox (secreted IFN-alpha)	3.000000e-09
GCST002783_270	Body mass index	5.000000e-06
GCST002783_625	Body mass index	6.000000e-06
GCST004208_2	Body mass index	4.000000e-08
GCST005196_217	Coronary artery disease	7.000000e-06
GCST006463_6	Urinary albumin excretion (no hypertensive medication)	2.000000e-08
GCST006586_22	Urinary albumin excretion	5.000000e-09
GCST006976_39	Macular thickness	2.000000e-16
GCST007267_82	Systolic blood pressure	5.000000e-10
GCST008362_206	Birth weight	2.000000e-12
GCST008790_14	Urinary albumin-to-creatinine ratio	9.000000e-11
GCST008794_27	Urinary albumin-to-creatinine ratio	2.000000e-11
GCST009640_39	Urinary albumin-to-creatinine ratio	3.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004340	body mass index
EFO:0004285	albuminuria
EFO:0006335	systolic blood pressure
EFO:0004344	birth weight
EFO:0007778	urinary albumin to creatinine ratio

MeSH disease descriptors (15)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D005921	Glomerulonephritis	C12.050.351.968.419.570.363; C12.200.777.419.570.363; C12.950.419.570.363
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D006973	Hypertension	C14.907.489
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
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
D008575	Meniere Disease	C09.218.568.217.500
D009216	Myopia	C11.744.636
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625
D011507	Proteinuria	C12.050.351.968.934.734; C12.200.777.934.734; C12.950.934.734; C23.888.942.750
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
C562476	Hematuria, Benign Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364188 (PROTEIN COMPLEX GROUP), CHEMBL3988505 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Vorinostat	affects cotreatment, increases expression	2
Doxorubicin	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
evodiamine	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Methotrexate	increases expression	1
Nickel	increases expression	1
Phenobarbital	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases expression	1
Vitallium	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1

Cellosaurus cell lines

7 cell lines: 5 induced pluripotent stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1NX	Abcam HeLa COL4A4 KO	Cancer cell line	Female
CVCL_B5IV	NCKDi005-A	Induced pluripotent stem cell	Male
CVCL_E0AM	Ubigene HeLa COL4A4 KO	Cancer cell line	Female
CVCL_IX43	HPSI0416i-sevr_1	Induced pluripotent stem cell	Female
CVCL_IX44	HPSI0416i-sevr_2	Induced pluripotent stem cell	Female
CVCL_LF15	HPSI0516i-yist_1	Induced pluripotent stem cell	Male
CVCL_LF16	HPSI0516i-yist_3	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05655728	PHASE4	UNKNOWN	Treatment With Metformin in Chinese Children With Alport Syndrome
NCT06499948	PHASE4	ACTIVE_NOT_RECRUITING	Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients With Alport Syndrome (COMBINE-ALPORT)
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT03749447	PHASE3	TERMINATED	An Extended Access Program for Bardoxolone Methyl in Patients With CKD (EAGLE)
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT07523581	PHASE2	NOT_YET_RECRUITING	EXACT Study: A Blinded Study in Patients With Alport Syndrome to Evaluate Exaluren Efficacy and Safety
NCT00309257	PHASE2	COMPLETED	Effects of an Intensified Treatment With ACE-I,ATA II and Statins in Alport Syndrome
NCT02855268	PHASE2	TERMINATED	Study of Lademirsen (SAR339375) in Patients With Alport Syndrome
NCT04573920	PHASE2	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With Proteinuric Glomerular Diseases
NCT05003986	PHASE2	RECRUITING	Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases
NCT05267262	PHASE2	COMPLETED	Study to Evaluate R3R01 in Patients With Alport Syndrome and Patients With Focal Segmental Glomerulosclerosis
NCT05448755	PHASE2	COMPLETED	A Study of ELX-02 in Patients With Alport Syndrome
NCT06425055	PHASE2	COMPLETED	Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1)
NCT07211685	PHASE2	RECRUITING	BAY3401016; Biomarker Study Alport
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph