COL4A5
collagen type IV alpha 5 chain, the group of Collagens
Basic information
Region (hg38): X:108439838-108697545
Previous symbols: [ "ASLN", "ATS" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- not provided (315 variants)
- X-linked Alport syndrome (170 variants)
- Alport syndrome (13 variants)
- COL4A5-related disorder (7 variants)
- Inborn genetic diseases (3 variants)
- See cases (2 variants)
- Focal segmental glomerulosclerosis (1 variants)
- Downslanted palpebral fissures;Proteinuria;Hematuria;Kidney damage (1 variants)
- Nephrotic syndrome (1 variants)
- Autosomal dominant Alport syndrome (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 | 408 | 25 | 440 | |||
| missense | 148 | 340 | 216 | 108 | 24 | 836 |
| nonsense | 59 | 48 | 107 | |||
| start loss | 3 | |||||
| frameshift | 122 | 63 | 185 | |||
| inframe indel | 10 | 25 | ||||
| splice donor/acceptor (+/-2bp) | 85 | 50 | 135 | |||
| splice region | 3 | 6 | 44 | 107 | 9 | 169 |
| non coding | 27 | 274 | 78 | 393 | ||
| Total | 430 | 520 | 256 | 791 | 127 |
Highest pathogenic variant AF is 0.00000897
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-108440135-C-A | not specified | Uncertain significance (Apr 10, 2024) | ||
| 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) |
GnomAD
Source:
| 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:
- 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