TIGAR

TP53 induced glycolysis regulatory phosphatase, the group of Sugar phosphatases

Basic information

Region (hg38): 12:4307763-4360028

Previous symbols: [ "C12orf5" ]

Links

ENSG00000078237 ∙ NCBI:57103 ∙ OMIM:610775 ∙ HGNC:1185 ∙ Uniprot:Q9NQ88 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIGAR 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						0
missense			4	2		6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	4	2	0

Variants in TIGAR

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

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

Position	Type	Phenotype	Significance	ClinVar
12-4331308-A-G		not specified	Uncertain significance (Nov 12, 2021)
12-4337081-A-G		not specified	Uncertain significance (Dec 01, 2022)
12-4337110-A-C		not specified	Uncertain significance (Apr 01, 2024)
12-4349849-T-G		not specified	Likely benign (Apr 13, 2023)
12-4352413-A-G		not specified	Likely benign (Dec 18, 2023)
12-4352543-G-A		not specified	Uncertain significance (May 01, 2024)
12-4352621-T-G		not specified	Uncertain significance (Dec 08, 2023)
12-4352629-A-G		not specified	Uncertain significance (Feb 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIGAR	protein_coding	protein_coding	ENST00000179259	6	31968

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.735	0.263	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	101	149	0.678	0.00000766	1770
Missense in Polyphen		8	33.316	0.24012		369
Synonymous	0.546	47	52.0	0.904	0.00000294	515
Loss of Function	2.42	1	8.71	0.115	3.67e-7	112

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000468	0.0000462
European (Non-Finnish)	0.0000271	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Fructose-bisphosphatase hydrolyzing fructose-2,6- bisphosphate as well as fructose-1,6-bisphosphate (PubMed:19015259). Acts as a negative regulator of glycolysis by lowering intracellular levels of fructose-2,6-bisphosphate in a p53/TP53-dependent manner, resulting in the pentose phosphate pathway (PPP) activation and NADPH production (PubMed:16839880, PubMed:22887998). Contributes to the generation of reduced glutathione to cause a decrease in intracellular reactive oxygen species (ROS) content, correlating with its ability to protect cells from oxidative or metabolic stress-induced cell death (PubMed:16839880, PubMed:19713938, PubMed:23726973, PubMed:22887998, PubMed:23817040). Plays a role in promoting protection against cell death during hypoxia by decreasing mitochondria ROS levels in a HK2-dependent manner through a mechanism that is independent of its fructose-bisphosphatase activity (PubMed:23185017). In response to cardiac damage stress, mediates p53-induced inhibition of myocyte mitophagy through ROS levels reduction and the subsequent inactivation of BNIP3. Reduced mitophagy results in an enhanced apoptotic myocyte cell death, and exacerbates cardiac damage (By similarity). Plays a role in adult intestinal regeneration; contributes to the growth, proliferation and survival of intestinal crypts following tissue ablation (PubMed:23726973). Plays a neuroprotective role against ischemic brain damage by enhancing PPP flux and preserving mitochondria functions (By similarity). Protects glioma cells from hypoxia- and ROS-induced cell death by inhibiting glycolysis and activating mitochondrial energy metabolism and oxygen consumption in a TKTL1- dependent and p53/TP53-independent manner (PubMed:22887998). Plays a role in cancer cell survival by promoting DNA repair through activating PPP flux in a CDK5-ATM-dependent signaling pathway during hypoxia and/or genome stress-induced DNA damage responses (PubMed:25928429). Involved in intestinal tumor progression (PubMed:23726973). {ECO:0000250|UniProtKB:Q8BZA9, ECO:0000269|PubMed:16839880, ECO:0000269|PubMed:19015259, ECO:0000269|PubMed:19713938, ECO:0000269|PubMed:22887998, ECO:0000269|PubMed:23185017, ECO:0000269|PubMed:23726973, ECO:0000269|PubMed:23817040, ECO:0000269|PubMed:25928429}.
• Pathway: Fructose and mannose metabolism - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);TP53 Regulates Metabolic Genes;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;fructose 2,6-bisphosphate synthesis;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;Direct p53 effectors (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

• pHI: 0.0647
• hipred: N
• hipred_score: 0.398
• ghis: 0.544

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Tigar
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; immune system phenotype; digestive/alimentary phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: response to ischemia;fructose 2,6-bisphosphate metabolic process;autophagy;apoptotic process;cellular response to DNA damage stimulus;response to xenobiotic stimulus;response to gamma radiation;positive regulation of cardiac muscle cell apoptotic process;dephosphorylation;fructose 1,6-bisphosphate metabolic process;negative regulation of programmed cell death;regulation of pentose-phosphate shunt;positive regulation of DNA repair;negative regulation of glycolytic process;intestinal epithelial cell development;cellular response to cobalt ion;cellular response to hypoxia;negative regulation of neuron death;negative regulation of mitophagy;regulation of response to DNA damage checkpoint signaling;positive regulation of hexokinase activity;negative regulation of glucose catabolic process to lactate via pyruvate;negative regulation of reactive oxygen species metabolic process
• Cellular component: nucleus;cytoplasm;mitochondrial outer membrane;cytosol
• Molecular function: bisphosphoglycerate 2-phosphatase activity;fructose-2,6-bisphosphate 2-phosphatase activity;protein binding