FTCD

formimidoyltransferase cyclodeaminase

Basic information

Region (hg38): 21:46136159-46155579

Links

ENSG00000160282 ∙ NCBI:10841 ∙ OMIM:606806 ∙ HGNC:3974 ∙ Uniprot:O95954 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• formiminoglutamic aciduria (Definitive), mode of inheritance: AR
• formiminoglutamic aciduria (Moderate), mode of inheritance: AR
• formiminoglutamic aciduria (Strong), mode of inheritance: AR
• formiminoglutamic aciduria (Supportive), mode of inheritance: AR
• formiminoglutamic aciduria (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glutamate formiminotransferase deficiency	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical	5897668; 5956503; 4413489; 235753; 1272625; 12815595; 22108709; 29178637
Early descriptions included benefits of folic acid treatment, but later descriptions call this into question, and the clinical consequences of the deficiency are unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FTCD gene.

• Glutamate formiminotransferase deficiency (207 variants)
• Inborn genetic diseases (51 variants)
• not provided (41 variants)
• not specified (10 variants)
• Intellectual disability (8 variants)
• Myosclerosis (5 variants)
• Collagen 6-related myopathy (5 variants)
• FTCD-related condition (3 variants)
• Myoepithelial tumor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FTCD 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			2	33	8	43
missense			103	20	8	131
nonsense	2	2				4
start loss						0
frameshift	1	1	4			6
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region			5	6		11
non coding			5	28	13	46
Total	3	3	118	81	29

Highest pathogenic variant AF is 0.0000394

Variants in FTCD

This is a list of pathogenic ClinVar variants found in the FTCD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-46136261-G-A		Myosclerosis • Collagen 6-related myopathy	Likely benign (Jun 14, 2016)
21-46136370-G-T		Myosclerosis • Glutamate formiminotransferase deficiency • Collagen 6-related myopathy • COL6A2-related disorder	Conflicting classifications of pathogenicity (Sep 07, 2022)
21-46136384-G-A		Glutamate formiminotransferase deficiency	Uncertain significance (Jun 14, 2016)
21-46136430-G-A		Glutamate formiminotransferase deficiency • Myosclerosis • Collagen 6-related myopathy	Conflicting classifications of pathogenicity (Jun 14, 2016)
21-46136482-G-T		Glutamate formiminotransferase deficiency • Myosclerosis • Collagen 6-related myopathy • FTCD-related disorder	Conflicting classifications of pathogenicity (Apr 08, 2019)
21-46136879-C-T		Glutamate formiminotransferase deficiency	Benign (Aug 10, 2021)
21-46136907-G-C		FTCD-related disorder	Likely benign (Feb 19, 2019)
21-46136968-G-A		not specified	Benign (Mar 12, 2013)
21-46136980-C-T			Uncertain significance (Nov 29, 2022)
21-46136986-G-A		Glutamate formiminotransferase deficiency	Uncertain significance (Jun 14, 2016)
21-46136998-G-A		Glutamate formiminotransferase deficiency • Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
21-46136999-G-A		Glutamate formiminotransferase deficiency	Likely benign (Nov 22, 2022)
21-46137005-C-T		Glutamate formiminotransferase deficiency	Likely benign (Dec 11, 2023)
21-46137006-A-T		Glutamate formiminotransferase deficiency • not specified	Conflicting classifications of pathogenicity (Mar 28, 2024)
21-46137022-G-T		Glutamate formiminotransferase deficiency	Uncertain significance (Aug 19, 2022)
21-46137023-T-C		Glutamate formiminotransferase deficiency	Likely benign (Apr 24, 2019)
21-46137024-G-A		Glutamate formiminotransferase deficiency • Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
21-46137030-T-G			Uncertain significance (Jan 21, 2014)
21-46137036-T-C			Uncertain significance (Feb 01, 2018)
21-46137039-G-A		Glutamate formiminotransferase deficiency	Uncertain significance (Feb 19, 2023)
21-46137050-G-A		Glutamate formiminotransferase deficiency	Likely benign (Nov 17, 2023)
21-46137063-C-T			Uncertain significance (Oct 23, 2019)
21-46137064-G-A		Glutamate formiminotransferase deficiency • Inborn genetic diseases	Uncertain significance (Feb 24, 2022)
21-46137068-G-A		Glutamate formiminotransferase deficiency	Likely benign (Feb 24, 2022)
21-46137070-G-A		Inborn genetic diseases	Uncertain significance (Apr 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FTCD	protein_coding	protein_coding	ENST00000291670	14	19306

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.52e-15	0.0523	125547	1	182	125730	0.000728

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.350	357	339	1.05	0.0000245	3393
Missense in Polyphen		139	139.24	0.99824		1322
Synonymous	-1.85	186	156	1.19	0.0000122	1159
Loss of Function	0.616	24	27.5	0.873	0.00000143	295

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00554	0.00546
Ashkenazi Jewish	0.00472	0.00428
East Asian	0.000274	0.000272
Finnish	0.000103	0.0000924
European (Non-Finnish)	0.000223	0.000211
Middle Eastern	0.000274	0.000272
South Asian	0.000294	0.000294
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool.
• Disease: DISEASE: Glutamate formiminotransferase deficiency (FIGLU-URIA) [MIM:229100]: Autosomal recessive disorder. Features of a severe phenotype, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities. {ECO:0000269|PubMed:12815595}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: One carbon pool by folate - Homo sapiens (human);Histidine metabolism - Homo sapiens (human);Folate malabsorption, hereditary;Histidine Metabolism;Methylenetetrahydrofolate Reductase Deficiency (MTHFRD);Methotrexate Action Pathway;Folate Metabolism;Histidinemia;One Carbon Metabolism;Amino Acid metabolism;Histidine catabolism;Folate metabolism;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Metabolism;histidine degradation;Vitamin B9 (folate) metabolism;Histidine degradation (Consensus)

Intolerance Scores

• loftool: 0.365
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.74

Haploinsufficiency Scores

• pHI: 0.131
• hipred: N
• hipred_score: 0.170
• ghis: 0.488

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.806

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ftcd

Gene ontology

• Biological process: histidine catabolic process;folic acid-containing compound metabolic process;cytoskeleton organization;histidine catabolic process to glutamate and formamide;histidine catabolic process to glutamate and formate;tetrahydrofolate interconversion
• Cellular component: Golgi membrane;cytoplasm;endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;Golgi apparatus;centriole;cytosol;plasma membrane;smooth endoplasmic reticulum membrane;extracellular exosome
• Molecular function: protein binding;folic acid binding;microtubule binding;formimidoyltransferase activity;glutamate formimidoyltransferase activity;formimidoyltetrahydrofolate cyclodeaminase activity