Reviewed September 2010
What is the official name of the TCIRG1 gene?
The official name of this gene is “T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 subunit A3.”
TCIRG1 is the gene's official symbol. The TCIRG1 gene is also known by other names, listed below.
What is the normal function of the TCIRG1 gene?
The TCIRG1 gene provides instructions for making one part, the a3 subunit, of a large protein complex known as a vacuolar H+-ATPase (V-ATPase). V-ATPases are a group of similar complexes that act as pumps to move positively charged hydrogen atoms (protons) across membranes. This movement of protons helps regulate the relative acidity (pH) of cells and their surrounding environment. Tight control of pH is necessary for most biological reactions to proceed properly.
The V-ATPases containing the a3 subunit play an essential role in specialized cells called osteoclasts. These cells break down bone tissue as part of the normal process of bone remodeling, in which old bone is removed and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy.
On the surface of osteoclasts, V-ATPases are embedded in a specialized, highly folded membrane called the ruffled border. The ruffled border faces the surface of bone, where it helps form a tightly sealed compartment between the osteoclast and the bone surface. V-ATPases pump protons into the compartment, making it very acidic. This acidic environment is necessary to break down bone.
Does the TCIRG1 gene share characteristics with other genes?
The TCIRG1 gene belongs to a family of genes called ATP (ATPase superfamily).
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 TCIRG1 gene related to health conditions?
- osteopetrosis - caused by mutations in the TCIRG1 gene
More than 60 mutations in the TCIRG1 gene have been identified in people with osteopetrosis. These mutations cause the most severe form of the disorder, autosomal recessive osteopetrosis (ARO).
Many TCIRG1 gene mutations change how the gene's instructions are used to make the a3 subunit of V-ATPase. Other mutations change single protein building blocks (amino acids) in the a3 subunit or lead to the production of an abnormally short version of the subunit. Studies suggest that most of the TCIRG1 gene mutations responsible for osteopetrosis eliminate the function of the a3 subunit.
Without the a3 subunit, V-ATPases cannot pump protons out of osteoclasts. As a result, the compartment between the ruffled border and the bone surface is not acidified, and bone cannot be broken down. When old bone is not broken down as new bone is formed, bones throughout the skeleton become unusually dense. The bones are also structurally abnormal, making them prone to fracture. These problems with bone remodeling underlie the major features of autosomal recessive osteopetrosis.
Where is the TCIRG1 gene located?
Cytogenetic Location: 11q13.2
Molecular Location on chromosome 11: base pairs 67,806,461 to 67,818,365
The TCIRG1 gene is located on the long (q) arm of chromosome 11 at position 13.2.
More precisely, the TCIRG1 gene is located from base pair 67,806,461 to base pair 67,818,365 on chromosome 11.
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 TCIRG1?
You and your healthcare professional may find the following resources about TCIRG1 helpful.
Educational resources - Information pages
- Molecular Biology of the Cell (fourth edition, 2002): An Osteoclast Shown in Cross-Section (image) (http://www.ncbi.nlm.nih.gov/books/NBK26889/?rendertype=figure&id=A4192)
- Molecular Biology of the Cell (fourth edition, 2002): Osteoblasts Secrete Bone Matrix, While Osteoclasts Erode It (http://www.ncbi.nlm.nih.gov/books/NBK26889/)
- Molecular Cell Biology (2000): V-Class H+ ATPases Pump Protons across Lysosomal and Vacuolar Membranes (http://www.ncbi.nlm.nih.gov/books/NBK21481/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for TCIRG1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=10312%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=(TCIRG1%5BTIAB%5D)%20OR%20((ATP6V0A3%5BTIAB%5D)%20OR%20(OC-116%5BTIAB%5D)%20OR%20(OC116%5BTIAB%5D)%20OR%20(TIRC7%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/604592)
Research Resources - Tools for researchers
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/10312)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=10312)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=11647)
- TCIRG1base: Mutation Registry for Autosomal Recessive Osteopetrosis (http://bioinf.uta.fi/TCIRG1base/)
What other names do people use for the TCIRG1 gene or gene products?
- ATPase, H+ transporting, 116kD
- OC-116 kDa
- osteoclastic proton pump 116 kDa subunit
- specific 116-kDa vacuolar proton pump subunit
- T-cell immune regulator 1
- T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein a
- T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein A3
- T-cell immune response cDNA 7
- T cell immune response cDNA7 protein
- T-cell immune response cDNA7 protein
- vacuolar proton translocating ATPase 116 kDa subunit A
- V-ATPase 116 kDa
- V-ATPase 116-kDa
- V-type proton ATPase 116 kDa subunit a
- V-type proton ATPase 116 kDa subunit a isoform 3
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 TCIRG1?
autosomal recessive ;
bone remodeling ;
immune response ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/10312)
- Frattini A, Orchard PJ, Sobacchi C, Giliani S, Abinun M, Mattsson JP, Keeling DJ, Andersson AK, Wallbrandt P, Zecca L, Notarangelo LD, Vezzoni P, Villa A. Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat Genet. 2000 Jul;25(3):343-6. (http://www.ncbi.nlm.nih.gov/pubmed/10888887?dopt=Abstract)
- Kornak U, Schulz A, Friedrich W, Uhlhaas S, Kremens B, Voit T, Hasan C, Bode U, Jentsch TJ, Kubisch C. Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. Hum Mol Genet. 2000 Aug 12;9(13):2059-63. (http://www.ncbi.nlm.nih.gov/pubmed/10942435?dopt=Abstract)
- Nishi T, Forgac M. The vacuolar (H+)-ATPases--nature's most versatile proton pumps. Nat Rev Mol Cell Biol. 2002 Feb;3(2):94-103. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11836511?dopt=Abstract)
- Scimeca JC, Quincey D, Parrinello H, Romatet D, Grosgeorge J, Gaudray P, Philip N, Fischer A, Carle GF. Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis. Hum Mutat. 2003 Feb;21(2):151-7. (http://www.ncbi.nlm.nih.gov/pubmed/12552563?dopt=Abstract)
- Sobacchi C, Frattini A, Orchard P, Porras O, Tezcan I, Andolina M, Babul-Hirji R, Baric I, Canham N, Chitayat D, Dupuis-Girod S, Ellis I, Etzioni A, Fasth A, Fisher A, Gerritsen B, Gulino V, Horwitz E, Klamroth V, Lanino E, Mirolo M, Musio A, Matthijs G, Nonomaya S, Notarangelo LD, Ochs HD, Superti Furga A, Valiaho J, van Hove JL, Vihinen M, Vujic D, Vezzoni P, Villa A. The mutational spectrum of human malignant autosomal recessive osteopetrosis. Hum Mol Genet. 2001 Aug 15;10(17):1767-73. (http://www.ncbi.nlm.nih.gov/pubmed/11532986?dopt=Abstract)
- Susani L, Pangrazio A, Sobacchi C, Taranta A, Mortier G, Savarirayan R, Villa A, Orchard P, Vezzoni P, Albertini A, Frattini A, Pagani F. TCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA. Hum Mutat. 2004 Sep;24(3):225-35. (http://www.ncbi.nlm.nih.gov/pubmed/15300850?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.