Reviewed December 2013
What is the official name of the COL4A4 gene?
The official name of this gene is “collagen type IV alpha 4.”
COL4A4 is the gene's official symbol. The COL4A4 gene is also known by other names, listed below.
What is the normal function of the COL4A4 gene?
The COL4A4 gene provides instructions for making one component of type IV collagen, which is a flexible protein. Specifically, this gene makes the alpha4(IV) chain of type IV collagen. This chain combines with two other types of alpha (IV) chains (the alpha3 and alpha5 chains) to make a complete type IV collagen molecule. Type IV collagen molecules attach to each other to form complex protein networks. These networks make up a large portion of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen alpha3-4-5 networks play an especially important role in the basement membranes of the kidney, inner ear, and eye.
Does the COL4A4 gene share characteristics with other genes?
The COL4A4 gene belongs to a family of genes called COL (collagens).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
How are changes in the COL4A4 gene related to health conditions?
- Alport syndrome - caused by mutations in the COL4A4 gene
More than 20 mutations in the COL4A4 gene have been found to cause Alport syndrome. Most of these mutations change single protein building blocks (amino acids) in a region where the alpha4(IV) collagen chain combines with other type IV collagen chains. Other mutations in the COL4A4 gene severely decrease or prevent the production of alpha4(IV) chains. As a result, there is a serious deficiency of the type IV collagen alpha3-4-5 network in the basement membranes of the kidney, inner ear, and eye. In the kidney, other types of collagen accumulate in the basement membranes, eventually leading to scarring of the kidneys and kidney failure. Mutations in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss.
- other disorders - caused by mutations in the COL4A4 gene
Mutations in the COL4A4 gene have been found to cause thin basement membrane nephropathy. This condition typically causes people to have blood in their urine (hematuria) but no other signs or symptoms of kidney disease. In the past, this condition was often called benign familial hematuria. Thin basement membrane nephropathy rarely progresses to kidney failure.
Where is the COL4A4 gene located?
Cytogenetic Location: 2q35-q37
Molecular Location on chromosome 2: base pairs 226,967,532 to 227,164,559
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/1286))
The COL4A4 gene is located on the long (q) arm of chromosome 2 between positions 35 and 37.
More precisely, the COL4A4 gene is located from base pair 226,967,532 to base pair 227,164,559 on chromosome 2.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about COL4A4?
You and your healthcare professional may find the following resources about COL4A4 helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth edition, 2002): A model of the molecular structure of a basal lamina (http://www.ncbi.nlm.nih.gov/books/NBK26810/?rendertype=figure&id=A3581)
- Molecular Biology of the Cell (fourth edition, 2002): Basal Laminae Perform Diverse Functions (http://www.ncbi.nlm.nih.gov/books/NBK26810/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1207)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for COL4A4 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=1286%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28COL4A4%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- COLLAGEN, TYPE IV, ALPHA-4 (http://omim.org/entry/120131)
- HEMATURIA, BENIGN FAMILIAL (http://omim.org/entry/141200)
Research Resources - Tools for researchers
- HGNC Gene Family: Collagens (http://www.genenames.org/cgi-bin/genefamilies/set/490)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=2206)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1286)
What other names do people use for the COL4A4 gene or gene products?
- alpha 4 type IV collagen
- Collagen IV, alpha-4 polypeptide
- collagen of basement membrane, alpha-4 chain
- collagen, type IV, alpha 4
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding COL4A4?
basement membrane ;
basement membranes ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Buzza M, Dagher H, Wang YY, Wilson D, Babon JJ, Cotton RG, Savige J. Mutations in the COL4A4 gene in thin basement membrane disease. Kidney Int. 2003 Feb;63(2):447-53. (http://www.ncbi.nlm.nih.gov/pubmed/12631110?dopt=Abstract)
- OMIM: COLLAGEN, TYPE IV, ALPHA-4 (http://omim.org/entry/120131)
- Gene Review: Alport Syndrome and Thin Basement Membrane Nephropathy (http://www.ncbi.nlm.nih.gov/books/NBK1207)
- Gregory MC. The clinical features of thin basement membrane nephropathy. Semin Nephrol. 2005 May;25(3):140-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15880323?dopt=Abstract)
- Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M. Novel COL4A4 splice defect and in-frame deletion in a large consanguine family as a genetic link between benign familial haematuria and autosomal Alport syndrome. Nephrol Dial Transplant. 2003 Jun;18(6):1122-7. (http://www.ncbi.nlm.nih.gov/pubmed/12748344?dopt=Abstract)
- Kashtan CE. Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes. Medicine (Baltimore). 1999 Sep;78(5):338-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10499074?dopt=Abstract)
- Longo I, Porcedda P, Mari F, Giachino D, Meloni I, Deplano C, Brusco A, Bosio M, Massella L, Lavoratti G, Roccatello D, Frascá G, Mazzucco G, Muda AO, Conti M, Fasciolo F, Arrondel C, Heidet L, Renieri A, De Marchi M. COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney Int. 2002 Jun;61(6):1947-56. (http://www.ncbi.nlm.nih.gov/pubmed/12028435?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1286)
- Pescucci C, Mari F, Longo I, Vogiatzi P, Caselli R, Scala E, Abaterusso C, Gusmano R, Seri M, Miglietti N, Bresin E, Renieri A. Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene. Kidney Int. 2004 May;65(5):1598-603. (http://www.ncbi.nlm.nih.gov/pubmed/15086897?dopt=Abstract)
- Rana K, Wang YY, Buzza M, Tonna S, Zhang KW, Lin T, Sin L, Padavarat S, Savige J. The genetics of thin basement membrane nephropathy. Semin Nephrol. 2005 May;25(3):163-70. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15880327?dopt=Abstract)
- Slajpah M, Gorinsek B, Berginc G, Vizjak A, Ferluga D, Hvala A, Meglic A, Jaksa I, Furlan P, Gregoric A, Kaplan-Pavlovcic S, Ravnik-Glavac M, Glavac D. Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney Int. 2007 Jun;71(12):1287-95. Epub 2007 Mar 28. (http://www.ncbi.nlm.nih.gov/pubmed/17396119?dopt=Abstract)
- Tazón Vega B, Badenas C, Ars E, Lens X, Milà M, Darnell A, Torra R. Autosomal recessive Alport's syndrome and benign familial hematuria are collagen type IV diseases. Am J Kidney Dis. 2003 Nov;42(5):952-9. (http://www.ncbi.nlm.nih.gov/pubmed/14582039?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.