GeneBe

COL4A5

collagen type IV alpha 5 chain, the group of Collagens

Basic information

Region (hg38): X:108439838-108697545

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
  • Alport syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Alport syndrome 1, X-linkedXLOphthalmologic; RenalIn 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 erosionsAudiologic/Otolaryngologic; Ophthalmologic; Renal20773074; 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 (2032 variants)
  • X-linked_Alport_syndrome (1182 variants)
  • Inborn_genetic_diseases (115 variants)
  • COL4A5-related_disorder (97 variants)
  • not_specified (84 variants)
  • Alport_syndrome (55 variants)
  • Kidney_disorder (9 variants)
  • Nephrotic_syndrome (6 variants)
  • Hematuria (5 variants)
  • Autosomal_dominant_Alport_syndrome (4 variants)
  • See_cases (4 variants)
  • Hearing_impairment (3 variants)
  • Microscopic_hematuria (3 variants)
  • Proteinuria (3 variants)
  • Atypical_hemolytic-uremic_syndrome (2 variants)
  • Nonsyndromic_genetic_hearing_loss (2 variants)
  • Mild_proteinuria (2 variants)
  • Haematuria (2 variants)
  • Rare_genetic_deafness (1 variants)
  • Unilateral_deafness (1 variants)
  • Phelan-McDermid_syndrome (1 variants)
  • Rare_disease_with_thoracic_aortic_aneurysm_and_aortic_dissection (1 variants)
  • Isolated_macular_dystrophy (1 variants)
  • Steroid-resistant_nephrotic_syndrome (1 variants)
  • Chronic_kidney_disease (1 variants)
  • Focal_segmental_glomerulosclerosis (1 variants)
  • Downslanted_palpebral_fissures (1 variants)
  • Familial_hematuria (1 variants)
  • Alport_syndrome_1 (1 variants)
  • Kidney_damage (1 variants)
  • Hypertensive_disorder (1 variants)
  • Disease_of_glomerular_basement_membrane (1 variants)
  • Elevated_mean_arterial_pressure (1 variants)
  • Glomerulopathy (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. These statistics are base on transcript: NM_000033380.3. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
4
clinvar
20
clinvar
437
clinvar
23
clinvar
 486
missense
195
clinvar
509
clinvar
396
clinvar
149
clinvar
19
clinvar
 1268
nonsense
73
clinvar
59
clinvar
 132
start loss
3
1
 4
frameshift
159
clinvar
109
clinvar
 268
splice donor/acceptor (+/-2bp)
99
clinvar
83
clinvar
 182
Total 531 765 416 586 42

Highest pathogenic variant AF is 0.000046288147

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
COL4A5protein_codingprotein_codingENST00000328300 53257702
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.000.00000307125728161257350.0000278
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.504746540.7250.000046710558
Missense in Polyphen66107.110.616181643
Synonymous-0.3562222151.030.00001593773
Loss of Function6.59661.90.09690.000004151163

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002300.000185
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00006260.0000462
European (Non-Finnish)0.00003770.0000264
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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