COL4A3
Basic information
Region (hg38): 2:227164624-227314792
Links
Phenotypes
GenCC
Source:
- autosomal recessive Alport syndrome (Definitive), mode of inheritance: AR
- autosomal recessive Alport syndrome (Definitive), mode of inheritance: AR
- hematuria, benign familial, 1 (Strong), mode of inheritance: AD
- autosomal dominant Alport syndrome (Strong), mode of inheritance: AD
- autosomal recessive Alport syndrome (Strong), mode of inheritance: AR
- autosomal recessive Alport syndrome (Strong), mode of inheritance: AR
- autosomal dominant Alport syndrome (Supportive), mode of inheritance: AD
- autosomal recessive Alport syndrome (Supportive), mode of inheritance: AR
- autosomal recessive Alport syndrome (Strong), mode of inheritance: AR
- autosomal dominant Alport syndrome (Definitive), mode of inheritance: AD
- hematuria, benign familial, 1 (Strong), mode of inheritance: AD
- Alport syndrome (Definitive), mode of inheritance: Semidominant
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Alport syndrome 3A, autosomal dominant; Alport syndrome 3B, autosomal recessive | AD/AR | 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 | 7033680; 7987301; 8196274; 7987396; 7783412; 7783419; 9195222; 9269635; 11961012; 11134255; 20301386; 22166847; 22237748; 22811928; 22997344; 23927549 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (159 variants)
- Autosomal dominant Alport syndrome (23 variants)
- Autosomal recessive Alport syndrome (22 variants)
- Autosomal dominant Alport syndrome;Autosomal recessive Alport syndrome;Benign familial hematuria (12 variants)
- Alport syndrome (11 variants)
- Benign familial hematuria (3 variants)
- Alport syndrome 3b, autosomal recessive (3 variants)
- COL4A3-related disorder (1 variants)
- Benign familial hematuria;Autosomal dominant Alport syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL4A3 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 | 569 | 579 | ||||
missense | 26 | 115 | 341 | 48 | 13 | 543 |
nonsense | 42 | 58 | 101 | |||
start loss | 3 | |||||
frameshift | 88 | 62 | 152 | |||
inframe indel | 13 | 23 | ||||
splice donor/acceptor (+/-2bp) | 22 | 90 | 116 | |||
splice region | 3 | 1 | 26 | 151 | 8 | 189 |
non coding | 51 | 456 | 146 | 654 | ||
Total | 181 | 335 | 417 | 1076 | 162 |
Highest pathogenic variant AF is 0.0000460
Variants in COL4A3
This is a list of pathogenic ClinVar variants found in the COL4A3 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
2-227164646-G-C | Alport syndrome | Uncertain significance (Jan 12, 2018) | ||
2-227164701-G-T | Alport syndrome | Conflicting classifications of pathogenicity (Jun 07, 2018) | ||
2-227164711-T-C | Alport syndrome | Uncertain significance (Jan 13, 2018) | ||
2-227164714-G-C | Alport syndrome • not specified | Conflicting classifications of pathogenicity (Mar 09, 2018) | ||
2-227164717-C-T | Alport syndrome • not specified • Autosomal dominant Alport syndrome • COL4A3-related disorder | Conflicting classifications of pathogenicity (Dec 18, 2023) | ||
2-227164726-C-T | Uncertain significance (Jun 05, 2024) | |||
2-227164727-A-C | Autosomal recessive Alport syndrome • Alport syndrome | Pathogenic/Likely pathogenic (Jun 14, 2022) | ||
2-227164727-A-G | Pathogenic (Oct 31, 2022) | |||
2-227164728-T-C | Autosomal recessive Alport syndrome | Likely pathogenic (Mar 07, 2018) | ||
2-227164732-C-G | Uncertain significance (Mar 15, 2024) | |||
2-227164732-C-T | Likely benign (Dec 09, 2023) | |||
2-227164733-G-A | COL4A3-related disorder | Uncertain significance (Aug 28, 2024) | ||
2-227164737-G-A | Alport syndrome • Autosomal dominant Alport syndrome;Autosomal recessive Alport syndrome;Benign familial hematuria | Uncertain significance (Mar 17, 2023) | ||
2-227164738-G-T | Likely benign (May 20, 2023) | |||
2-227164741-C-A | Likely benign (Apr 10, 2023) | |||
2-227164741-C-G | Likely benign (Aug 06, 2022) | |||
2-227164741-C-T | Likely benign (Mar 24, 2021) | |||
2-227164742-G-T | not specified | Uncertain significance (Nov 02, 2022) | ||
2-227164743-C-A | Uncertain significance (Dec 14, 2023) | |||
2-227164744-C-T | Likely benign (Jun 20, 2023) | |||
2-227164747-C-A | not specified • Autosomal dominant Alport syndrome;Autosomal recessive Alport syndrome;Benign familial hematuria | Likely benign (Jan 29, 2024) | ||
2-227164747-C-T | Likely benign (Dec 29, 2023) | |||
2-227164748-A-C | Likely benign (Jul 25, 2023) | |||
2-227164751-C-T | Autosomal dominant Alport syndrome;Autosomal recessive Alport syndrome;Benign familial hematuria | Conflicting classifications of pathogenicity (Jan 05, 2024) | ||
2-227164752-C-T | not specified | Uncertain significance (Dec 13, 2023) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
COL4A3 | protein_coding | protein_coding | ENST00000396578 | 52 | 150228 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
1.07e-12 | 1.00 | 124648 | 0 | 146 | 124794 | 0.000585 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.99 | 763 | 935 | 0.816 | 0.0000484 | 10352 |
Missense in Polyphen | 144 | 201.02 | 0.71635 | 2111 | ||
Synonymous | 0.537 | 315 | 327 | 0.962 | 0.0000186 | 3697 |
Loss of Function | 5.45 | 38 | 95.4 | 0.398 | 0.00000489 | 1208 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00157 | 0.00157 |
Ashkenazi Jewish | 0.000199 | 0.000199 |
East Asian | 0.000392 | 0.000389 |
Finnish | 0.000279 | 0.000278 |
European (Non-Finnish) | 0.000533 | 0.000530 |
Middle Eastern | 0.000392 | 0.000389 |
South Asian | 0.000761 | 0.000752 |
Other | 0.000831 | 0.000825 |
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: Note=Autoantibodies against the NC1 domain of alpha 3(IV) are found in Goodpasture syndrome, an autoimmune disease of lung and kidney.; DISEASE: Alport syndrome, autosomal recessive (APSAR) [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. {ECO:0000269|PubMed:11134255, ECO:0000269|PubMed:15954103, ECO:0000269|PubMed:29946535}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hematuria, benign familial (BFH) [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. {ECO:0000269|PubMed:11961012}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Alport syndrome, autosomal dominant (APSAD) [MIM:104200]: 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. {ECO:0000269|PubMed:11044206, ECO:0000269|PubMed:11134255}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- 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;Integrin cell surface interactions;Signaling by PDGF;Collagen formation;Extracellular matrix organization;Beta3 integrin cell surface interactions;Integrin;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis
(Consensus)
Recessive Scores
- pRec
- 0.340
Intolerance Scores
- loftool
- 0.0989
- rvis_EVS
- 1.35
- rvis_percentile_EVS
- 94.31
Haploinsufficiency Scores
- pHI
- 0.292
- hipred
- Y
- hipred_score
- 0.575
- ghis
- 0.415
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.461
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | High | High | High |
Primary Immunodeficiency | High | High | High |
Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Col4a3
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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);
Gene ontology
- Biological process
- activation of cysteine-type endopeptidase activity involved in apoptotic process;cell adhesion;cell surface receptor signaling pathway;sensory perception of sound;blood circulation;cell population proliferation;negative regulation of cell population proliferation;response to glucose;negative regulation of endopeptidase activity;negative regulation of angiogenesis;extracellular matrix organization;glomerular basement membrane development;collagen-activated tyrosine kinase receptor signaling pathway;endothelial cell apoptotic process
- Cellular component
- extracellular region;collagen type IV trimer;basement membrane;extracellular space;endoplasmic reticulum;endoplasmic reticulum lumen;extracellular matrix;intracellular membrane-bounded organelle;collagen-containing extracellular matrix
- Molecular function
- integrin binding;structural molecule activity;extracellular matrix structural constituent;protein binding;metalloendopeptidase inhibitor activity;extracellular matrix structural constituent conferring tensile strength