COL4A5

collagen type IV alpha 5 chain, the group of Collagens

Basic information

Region (hg38): X:108439837-108697545

Previous symbols: [ "ASLN", "ATS" ]

Links

ENSG00000188153 ∙ NCBI:1287 ∙ OMIM:303630 ∙ HGNC:2207 ∙ Uniprot:P29400 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked Alport syndrome (Definitive), mode of inheritance: XL
• X-linked Alport syndrome (Strong), mode of inheritance: XL
• X-linked Alport syndrome (Strong), mode of inheritance: XL
• X-linked Alport syndrome (Supportive), mode of inheritance: XL
• X-linked Alport syndrome (Strong), mode of inheritance: XL
• Alport syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alport syndrome 1, X-linked	XL	Ophthalmologic; Renal	In Alport syndrome, medical treatment related to renal sequelae (eg, with ACE inhibitors, ARBs) may be beneficial related to delaying renal failure, as well as with overall life expectancy, though dialysis/renal transplantation may be required; Corneal protection may be beneficial in individuals with recurrent corneal erosions	Audiologic/Otolaryngologic; Ophthalmologic; Renal	20773074; 14856448; 626446; 7033680; 3728466; 2349482; 1483700; 1635357; 1598909; 7706490; 8825605; 8651292; 8940267; 8651296; 9195222; 20881942; 21505094; 21848006; 21897443; 21332469; 22166944; 20301386; 22166847; 22237748; 22335431; 22811928; 22921432; 22919268; 22997344
Treatment of renal issues (eg, with antihypertensive agents, ACE inhibitors, etc.) can be helpful, but does not appear to affect natural history

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL4A5 gene.

• not provided (1608 variants)
• X-linked Alport syndrome (611 variants)
• not specified (54 variants)
• Inborn genetic diseases (35 variants)
• COL4A5-related condition (35 variants)
• Alport syndrome (29 variants)
• Kidney disorder (9 variants)
• Autosomal dominant Alport syndrome (3 variants)
• Nephritis (2 variants)
• Focal segmental glomerulosclerosis (2 variants)
• See cases (2 variants)
• Nephrotic syndrome (2 variants)
• Hearing impairment (2 variants)
• Nonsyndromic genetic hearing loss (2 variants)
• Atypical hemolytic-uremic syndrome (2 variants)
• Proteinuria;Hematuria (1 variants)
• Mild proteinuria;Unilateral deafness;Microscopic hematuria (1 variants)
• Hematuria;Kidney damage;Proteinuria;Downslanted palpebral fissures (1 variants)
• Rare genetic deafness (1 variants)
• Disease of glomerular basement membrane (1 variants)
• Rare disease with thoracic aortic aneurysm and aortic dissection (1 variants)
• Hematuria (1 variants)
• Isolated macular dystrophy (1 variants)
• - (1 variants)
• Hematuria;Microscopic hematuria (1 variants)
• Phelan-McDermid syndrome (1 variants)
• Hypertensive disorder;Glomerulopathy;Mild proteinuria (1 variants)
• Hearing impairment;Proteinuria;Hematuria (1 variants)
• Chronic kidney disease;Elevated mean arterial pressure;Microscopic hematuria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL4A5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	321	25	354
missense	137	297	197	99	27	757
nonsense	54	46				100
start loss	3					3
frameshift	104	60				164
inframe indel	4	11	5		1	21
splice donor/acceptor (+/-2bp)	75	50				125
splice region	2	5	39	90	10	146
non coding	5	8	23	153	74	263
Total	382	472	233	573	127

Highest pathogenic variant AF is 0.0000266

Variants in COL4A5

This is a list of pathogenic ClinVar variants found in the COL4A5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-108440099-T-TGAAGGAGCTGCGGGAGCC		X-linked Alport syndrome • not specified • COL4A5-related disorder	Conflicting classifications of pathogenicity (Dec 08, 2023)
X-108440110-C-T		not specified	Uncertain significance (Dec 08, 2023)
X-108440126-A-G		X-linked Alport syndrome	Pathogenic (Aug 04, 2020)
X-108440127-T-A		X-linked Alport syndrome	Pathogenic (-)
X-108440128-G-T			Pathogenic (Jun 05, 2023)
X-108440128-G-GA		X-linked Alport syndrome	Pathogenic (Feb 21, 2024)
X-108440134-G-A			Likely benign (Aug 31, 2023)
X-108440147-C-T			Likely benign (Aug 16, 2023)
X-108440155-C-T			Likely benign (Feb 18, 2023)
X-108440157-G-T		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
X-108440157-GC-TT			Uncertain significance (Oct 19, 2022)
X-108440158-C-T			Benign (Oct 07, 2022)
X-108440159-T-C			Likely benign (Nov 10, 2023)
X-108440164-CTT-C		X-linked Alport syndrome	Likely pathogenic (Feb 25, 2022)
X-108440165-T-G		not specified • X-linked Alport syndrome	Uncertain significance (Sep 18, 2019)
X-108440171-G-C		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
X-108440173-C-G			Likely benign (Jul 19, 2023)
X-108440173-CCT-C			Pathogenic (Sep 16, 2018)
X-108440176-G-A			Likely benign (May 22, 2023)
X-108440176-G-T			Likely benign (Aug 06, 2021)
X-108440180-C-G		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
X-108440182-T-C		COL4A5-related disorder	Likely benign (Nov 19, 2023)
X-108440182-TTGGGGGCA-T			Pathogenic (Jan 19, 2021)
X-108440183-T-C			Uncertain significance (Sep 17, 2021)
X-108440185-G-A		X-linked Alport syndrome	Likely pathogenic (Sep 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL4A5	protein_coding	protein_coding	ENST00000328300	53	257702

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000307	125728	1	6	125735	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.50	474	654	0.725	0.0000467	10558
Missense in Polyphen		66	107.11	0.61618		1643
Synonymous	-0.356	222	215	1.03	0.0000159	3773
Loss of Function	6.59	6	61.9	0.0969	0.00000415	1163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000230	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000626	0.0000462
European (Non-Finnish)	0.0000377	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Alport syndrome, X-linked (APSX) [MIM:301050]: A syndrome that is characterized by progressive glomerulonephritis, renal failure, sensorineural deafness, specific eye abnormalities (lenticonous and macular flecks), and glomerular basement membrane defects. The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness. {ECO:0000269|PubMed:10094548, ECO:0000269|PubMed:10561141, ECO:0000269|PubMed:10563487, ECO:0000269|PubMed:10684360, ECO:0000269|PubMed:10862091, ECO:0000269|PubMed:11004279, ECO:0000269|PubMed:11223851, ECO:0000269|PubMed:1352287, ECO:0000269|PubMed:1363780, ECO:0000269|PubMed:1376965, ECO:0000269|PubMed:1672282, ECO:0000269|PubMed:24522658, ECO:0000269|PubMed:7599631, ECO:0000269|PubMed:7853788, ECO:0000269|PubMed:8406498, ECO:0000269|PubMed:8651292, ECO:0000269|PubMed:8651296, ECO:0000269|PubMed:8829632, ECO:0000269|PubMed:8940267, ECO:0000269|PubMed:9150741, ECO:0000269|PubMed:9452056, ECO:0000269|PubMed:9848783}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Deletions covering the N-terminal regions of COL4A5 and COL4A6, which are localized in a head-to-head manner, are found in the chromosome Xq22.3 centromeric deletion syndrome. This results in a phenotype with features of diffuse leiomyomatosis and Alport syndrome (DL-ATS).
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Primary Focal Segmental Glomerulosclerosis FSGS;Protein alkylation leading to liver fibrosis;PI3K-Akt Signaling Pathway;EMT transition in Colorectal Cancer;Developmental Biology;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;regulators of bone mineralization;intrinsic prothrombin activation pathway;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Signaling by PDGF;Collagen formation;Extracellular matrix organization;Beta3 integrin cell surface interactions;Integrin;NCAM signaling for neurite out-growth;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;NCAM1 interactions;Axon guidance;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Intolerance Scores

• loftool: 0.00255
• rvis_EVS: -1.15
• rvis_percentile_EVS: 6.32

Haploinsufficiency Scores

• pHI: 0.878
• hipred: Y
• hipred_score: 0.605
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.222

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Col4a5
• Phenotype: renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: col4a5
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: neuromuscular junction development;extracellular matrix organization;collagen-activated tyrosine kinase receptor signaling pathway
• Cellular component: extracellular region;collagen type IV trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;neuromuscular junction;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength