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FTCD
formimidoyltransferase cyclodeaminase
The FTCD gene provides instructions for an enzyme crucial in the final steps of histidine breakdown, primarily functioning in the liver. The FTCD gene encodes the formimidoyltransferase-cyclodeaminase enzyme, which plays a bifunctional role in metabolism.
FTCD is located on the long (q) arm of chromosome 21, at band 21q22.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The FTCD gene provides genetic instructions for creating an enzyme known as formimidoyltransferase-cyclodeaminase. This enzyme is primarily located in the liver, though smaller quantities are also found in the kidneys and testes. The formimidoyltransferase-cyclodeaminase enzyme is considered bifunctional because it carries out two distinct enzymatic activities, both of which are critical for the breakdown of the amino acid histidine.
What the gene does
The formimidoyltransferase-cyclodeaminase enzyme, encoded by the FTCD gene, performs two key enzymatic functions. Its first role is as a transferase, moving a group of atoms from one molecule to another. Specifically, it converts formiminoglutamate (FIGLU) into 5-formiminotetrahydrofolate, a process that also yields the amino acid glutamate. The enzyme's second function is that of a deaminase, which involves removing a group of nitrogen and hydrogen atoms from molecules. In this capacity, it transforms 5-formiminotetrahydrofolate into another tetrahydrofolate molecule. These tetrahydrofolate molecules are vital for carrying one-carbon units, which are necessary for the synthesis of purines and pyrimidines, the fundamental building blocks of DNA and RNA. Both of these enzymatic actions constitute the final two steps in the metabolic pathway for breaking down the amino acid histidine.
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Chromosome location
The FTCD gene is situated on chromosome 21 at position 21q22.3. This specific location on the long arm (q) of chromosome 21 indicates its genomic address within the human genome.
Protein structure
The formimidoyltransferase-cyclodeaminase protein is composed of 541 amino acids and exhibits a modular structure. It includes a Formiminotransferase N-subdomain spanning amino acids 1-181 and a Formiminotransferase C-subdomain from amino acids 182-326. These are followed by a short Linker region from amino acids 327-334. The protein's second enzymatic activity is attributed to the Cyclodeaminase/cyclohydrolase domain, which comprises amino acids 335-541.
Key variants
Genetic variations within the FTCD gene can alter the function of the formimidoyltransferase-cyclodeaminase enzyme. These variants, sometimes referred to as mutations, can influence the enzyme's ability to perform its metabolic roles. Identifying and characterising these genetic changes is important for understanding their potential impact on health.
Sample of pathogenic variants
9 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1031_1061del | p.Val344fs | Pathogenic/Likely pathogenic | ★★☆☆ | Glutamate formiminotransferase deficiency |
c.1607T>A | p.Leu536Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Glutamate formiminotransferase deficiency |
c.211C>T | p.Arg71Ter | Pathogenic/Likely pathogenic | ★★☆☆ | FTCD-related disorder |
c.293dup | p.Val99fs | Pathogenic/Likely pathogenic | ★★☆☆ | Glutamate formiminotransferase deficiency |
c.763C>T | p.Arg255Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.990dup | p.Pro331fs | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
g.(?_47565311)_(47575437_?)del | - | Pathogenic | ★☆☆☆ | Glutamate formiminotransferase deficiency |
c.1082_1083insTCGGC | p.Ala362fs | Pathogenic | ★☆☆☆ | Glutamate formiminotransferase deficiency |
c.613dup | p.Glu205fs | Pathogenic | ★☆☆☆ | Glutamate formiminotransferase deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the FTCD gene are associated with glutamate formiminotransferase deficiency. This inherited metabolic disorder can lead to elevated levels of formiminoglutamate (FIGLU) detectable in urine. Historically, the condition was described with both mild and severe presentations, although some individuals with FTCD gene variants may not experience obvious health problems.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic FTCD variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The FTCD gene is recognised within the UK's genomic healthcare framework, as evidenced by its inclusion in NHS England's PanelApp. It is listed with a 'green' status on panels such as DDG2P, Intellectual disability, Likely inborn error of metabolism, and Undiagnosed metabolic disorders (R98), indicating strong evidence of its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the FTCD gene do?
The FTCD gene provides instructions for an enzyme called formimidoyltransferase-cyclodeaminase. This enzyme is bifunctional, playing a key role in the final stages of breaking down the amino acid histidine, primarily in the liver.
What is glutamate formiminotransferase deficiency?
Glutamate formiminotransferase deficiency is an inherited condition caused by variants in the FTCD gene. It can lead to increased levels of formiminoglutamate (FIGLU) in the urine due to impaired histidine metabolism.
Where is the FTCD gene located?
The FTCD gene is located on chromosome 21, specifically at position 21q22.3. This is its designated address within the human genome.
References
- Mao Y, Vyas NK, Vyas MN. Structure of the bifunctional and Golgi-associated formiminotransferase cyclodeaminase octamer. The EMBO journal. 2004. PMID: 15272307
- Hilton JF, Christensen KE, Watkins D. The molecular basis of glutamate formiminotransferase deficiency. Human mutation. 2003. PMID: 12815595
- Solans A, Estivill X, de la Luna S. Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency. Cytogenetics and cell genetics. 2000. PMID: 10773664