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Genetics Home Reference: your guide to understanding genetic conditions
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POLR3A

Reviewed June 2013

What is the official name of the POLR3A gene?

The official name of this gene is “polymerase (RNA) III (DNA directed) polypeptide A, 155kDa.”

POLR3A is the gene's official symbol. The POLR3A gene is also known by other names, listed below.

What is the normal function of the POLR3A gene?

The POLR3A gene provides instructions for making the largest part (subunit) of an enzyme called RNA polymerase III. This enzyme is involved in the production (synthesis) of ribonucleic acid (RNA), a chemical cousin of DNA. The RNA polymerase III enzyme attaches (binds) to DNA and synthesizes RNA in accordance with the instructions carried by the DNA, a process called transcription. RNA polymerase III helps synthesize several forms of RNA, including ribosomal RNA (rRNA) and transfer RNA (tRNA). Molecules of rRNA and tRNA assemble protein building blocks (amino acids) into working proteins; this process is essential for the normal functioning and survival of cells.

Does the POLR3A gene share characteristics with other genes?

The POLR3A gene belongs to a family of genes called POLR (RNA polymerase subunits).

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 POLR3A gene related to health conditions?

Pol III-related leukodystrophy - caused by mutations in the POLR3A gene

At least 27 POLR3A gene mutations have been associated with Pol III-related leukodystrophy. Leukodystrophies are conditions that involve abnormalities of the nervous system's white matter. White matter consists of nerve fibers covered by a fatty substance called myelin, which insulates nerve fibers and promotes the rapid transmission of nerve impulses. A reduced ability to form myelin (hypomyelination) leads to the signs and symptoms of Pol III-related leukodystrophy, which include intellectual disability and difficulty with coordinating movements (ataxia). Development of the teeth (dentition) is also abnormal in this disorder.

In Pol III-related leukodystrophy, POLR3A gene mutations may impair the ability of the subunits of the RNA polymerase III enzyme to assemble properly or result in an RNA polymerase III with impaired ability to bind to DNA. Reduced function of the RNA polymerase III molecule likely affects development and function of many parts of the body, but the relationship between POLR3A gene mutations and the specific signs and symptoms of this disorder is unknown.

People with Pol III-related leukodystrophy may have different combinations of its signs and symptoms. These varied combinations of clinical features were originally described as separate disorders. Affected individuals may be diagnosed with ataxia, delayed dentition, and hypomyelination (ADDH); hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); tremor-ataxia with central hypomyelination (TACH); leukodystrophy with oligodontia (LO); or hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). Because these disorders were later found to have the same genetic cause, researchers now group them as variations of the single condition Pol III-related leukodystrophy.

Where is the POLR3A gene located?

Cytogenetic Location: 10q22-q23

Molecular Location on chromosome 10: base pairs 77,975,148 to 78,029,539

The POLR3A gene is located on the long (q) arm of chromosome 10 between positions 22 and 23.

The POLR3A gene is located on the long (q) arm of chromosome 10 between positions 22 and 23.

More precisely, the POLR3A gene is located from base pair 77,975,148 to base pair 78,029,539 on chromosome 10.

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 POLR3A?

You and your healthcare professional may find the following resources about POLR3A helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the POLR3A gene or gene products?

  • ADDH
  • DNA-directed RNA polymerase III largest subunit
  • DNA-directed RNA polymerase III subunit A
  • DNA-directed RNA polymerase III subunit RPC1
  • HLD7
  • hRPC155
  • RNA polymerase III 155 kDa subunit
  • RNA polymerase III subunit C1
  • RNA polymerase III subunit C160
  • RNA polymerase III subunit RPC155-D
  • RPC1
  • RPC1_HUMAN
  • RPC155

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 POLR3A?

acids ; ataxia ; atrophy ; corpus callosum ; disability ; DNA ; DNA-directed RNA polymerase ; enzyme ; gene ; hypodontia ; hypogonadism ; hypogonadotropic ; hypoplasia ; leukodystrophy ; molecule ; nervous system ; oligodontia ; protein ; ribonucleic acid ; ribosomal RNA ; RNA ; RNA polymerase ; subunit ; syndrome ; synthesis ; transcription ; transfer RNA ; tremor ; tRNA ; white matter

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Bernard G, Chouery E, Putorti ML, Tétreault M, Takanohashi A, Carosso G, Clément I, Boespflug-Tanguy O, Rodriguez D, Delague V, Abou Ghoch J, Jalkh N, Dorboz I, Fribourg S, Teichmann M, Megarbane A, Schiffmann R, Vanderver A, Brais B. Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy. Am J Hum Genet. 2011 Sep 9;89(3):415-23. doi: 10.1016/j.ajhg.2011.07.014. Erratum in: Am J Hum Genet. 2012 Nov 2;91(5):972. (http://www.ncbi.nlm.nih.gov/pubmed/21855841?dopt=Abstract)
  • Daoud H, Tétreault M, Gibson W, Guerrero K, Cohen A, Gburek-Augustat J, Synofzik M, Brais B, Stevens CA, Sanchez-Carpintero R, Goizet C, Naidu S, Vanderver A, Bernard G. Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism. J Med Genet. 2013 Mar;50(3):194-7. doi: 10.1136/jmedgenet-2012-101357. Epub 2013 Jan 25. (http://www.ncbi.nlm.nih.gov/pubmed/23355746?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/11128)
  • OMIM: POLYMERASE III, RNA, SUBUNIT A (http://omim.org/entry/614258)
  • Potic A, Brais B, Choquet K, Schiffmann R, Bernard G. 4H syndrome with late-onset growth hormone deficiency caused by POLR3A mutations. Arch Neurol. 2012 Jul;69(7):920-3. (http://www.ncbi.nlm.nih.gov/pubmed/22451160?dopt=Abstract)
  • Saitsu H, Osaka H, Sasaki M, Takanashi J, Hamada K, Yamashita A, Shibayama H, Shiina M, Kondo Y, Nishiyama K, Tsurusaki Y, Miyake N, Doi H, Ogata K, Inoue K, Matsumoto N. Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. Am J Hum Genet. 2011 Nov 11;89(5):644-51. doi: 10.1016/j.ajhg.2011.10.003. Epub 2011 Oct 27. (http://www.ncbi.nlm.nih.gov/pubmed/22036171?dopt=Abstract)
  • Terao Y, Saitsu H, Segawa M, Kondo Y, Sakamoto K, Matsumoto N, Tsuji S, Nomura Y. Diffuse central hypomyelination presenting as 4H syndrome caused by compound heterozygous mutations in POLR3A encoding the catalytic subunit of polymerase III. J Neurol Sci. 2012 Sep 15;320(1-2):102-5. doi: 10.1016/j.jns.2012.07.005. Epub 2012 Jul 21. (http://www.ncbi.nlm.nih.gov/pubmed/22819058?dopt=Abstract)
  • Vanderver A, Tonduti D, Bernard G, Lai J, Rossi C, Carosso G, Quezado M, Wong K, Schiffmann R. More than hypomyelination in Pol-III disorder. J Neuropathol Exp Neurol. 2013 Jan;72(1):67-75. doi: 10.1097/NEN.0b013e31827c99d2. (http://www.ncbi.nlm.nih.gov/pubmed/23242285?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 healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2013
Published: January 19, 2015