TKFC

triokinase and FMN cyclase

Basic information

Region (hg38): 11:61333220-61353295

Previous symbols: [ "DAK" ]

Links

ENSG00000149476 ∙ NCBI:26007 ∙ OMIM:615844 ∙ HGNC:24552 ∙ Uniprot:Q3LXA3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Sengers syndrome (Supportive), mode of inheritance: AR
• triokinase and FMN cyclase deficiency syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Triokinase and FMN cyclase deficiency syndrome	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; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	32004446

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TKFC 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	3	5
missense		2	52	3	1	58
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	2	53	5	6

Variants in TKFC

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

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

Position	Type	Phenotype	Significance	ClinVar
11-61337980-G-A		not specified	Uncertain significance (Jun 05, 2023)
11-61338040-C-T		not specified	Uncertain significance (Sep 21, 2021)
11-61338041-G-T		not specified	Uncertain significance (Mar 02, 2023)
11-61338064-GAC-G		Triokinase and FMN cyclase deficiency syndrome	Uncertain significance (Mar 29, 2024)
11-61338104-G-T		not specified	Uncertain significance (Apr 28, 2023)
11-61338125-A-G		not specified	Uncertain significance (Mar 28, 2024)
11-61339053-C-T		Triokinase and FMN cyclase deficiency syndrome	Benign (Jul 30, 2021)
11-61339066-G-A		not specified	Uncertain significance (Oct 02, 2023)
11-61339077-A-G		not specified	Uncertain significance (Jul 25, 2023)
11-61339169-C-T			Likely benign (May 01, 2022)
11-61339260-C-T		not specified	Uncertain significance (Mar 20, 2023)
11-61339268-A-C		not specified	Uncertain significance (May 30, 2023)
11-61339276-G-C		not specified	Uncertain significance (Jan 30, 2024)
11-61339293-G-A			Likely benign (Oct 01, 2023)
11-61339314-G-A		not specified	Uncertain significance (Jun 16, 2024)
11-61339326-G-A		not specified	Uncertain significance (Sep 29, 2023)
11-61339347-A-G		not specified	Uncertain significance (Apr 22, 2024)
11-61339400-C-T		not specified	Uncertain significance (Dec 20, 2023)
11-61339401-G-A		not specified	Uncertain significance (Dec 18, 2023)
11-61339415-G-A		not specified	Uncertain significance (Apr 07, 2023)
11-61339420-G-C		Triokinase and FMN cyclase deficiency syndrome	Benign (Jul 30, 2021)
11-61339421-G-C		not specified	Uncertain significance (Jan 26, 2022)
11-61341481-G-A		not specified	Likely benign (Mar 06, 2023)
11-61341502-G-A		Triokinase and FMN cyclase deficiency syndrome	Benign (Jul 30, 2021)
11-61341833-G-A			Benign (Dec 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TKFC	protein_coding	protein_coding	ENST00000394900	17	20086

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.17e-12	0.277	125579	0	169	125748	0.000672

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.395	352	373	0.943	0.0000239	3617
Missense in Polyphen		144	148.42	0.97022		1454
Synonymous	0.610	151	161	0.939	0.0000108	1288
Loss of Function	1.04	21	26.8	0.784	0.00000114	318

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00285	0.00285
Ashkenazi Jewish	0.00	0.00
East Asian	0.00250	0.00250
Finnish	0.0000477	0.0000462
European (Non-Finnish)	0.000374	0.000316
Middle Eastern	0.00250	0.00250
South Asian	0.00116	0.00111
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes both the phosphorylation of dihydroxyacetone and of glyceraldehyde, and the splitting of ribonucleoside diphosphate-X compounds among which FAD is the best substrate. Represses IFIH1-mediated cellular antiviral response (PubMed:17600090). {ECO:0000250|UniProtKB:F1RKQ4, ECO:0000250|UniProtKB:Q4KLZ6, ECO:0000269|PubMed:16289032, ECO:0000269|PubMed:17600090, ECO:0000269|PubMed:4688871}.
• Pathway: Fructose and mannose metabolism - Homo sapiens (human);Glycerolipid metabolism - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);RIG-I-like Receptor Signaling;Fructose metabolism;Metabolism of carbohydrates;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Innate Immune System;Immune System;Metabolism;Fructose catabolism;sucrose degradation (Consensus)

Recessive Scores

• pRec: 0.298

Intolerance Scores

• rvis_EVS: -0.48
• rvis_percentile_EVS: 22.75

Haploinsufficiency Scores

• pHI: 0.363
• hipred: N
• hipred_score: 0.204
• ghis: 0.528

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Tkfc

Gene ontology

• Biological process: glycerol catabolic process;negative regulation of MDA-5 signaling pathway;cellular carbohydrate metabolic process;innate immune response;regulation of innate immune response;carbohydrate phosphorylation;fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate
• Cellular component: nucleus;cytosol;extracellular exosome
• Molecular function: glycerone kinase activity;protein binding;ATP binding;FAD-AMP lyase (cyclizing) activity;metal ion binding;triokinase activity