TPI1

triosephosphate isomerase 1

Basic information

Region (hg38): 12:6867119-6870948

Links

ENSG00000111669 ∙ NCBI:7167 ∙ OMIM:190450 ∙ HGNC:12009 ∙ Uniprot:P60174 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• triosephosphate isomerase deficiency (Strong), mode of inheritance: AR
• triosephosphate isomerase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Triosephosphate isomerase deficiency	AR	Allergy/Immunology/Infectious; Hematologic	Surveillance and early treatment for complications affecting other organ systems, such as hematologic complications and cardiomyopathy can be beneficial (RBC transfusions have been described as beneficial); Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Neurologic	2569601; 2876430; 3619568; 14242501; 1959537; 4065896; 6946452; 8244340; 8503454; 8639817; 9294216; 9338582; 10209987; 10782327; 10910933; 10916682; 11196750; 14984912; 17424909; 17879449; 19786097; 20374271; 21215915; 24056040

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TPI1 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPI1 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				23	3	26
missense		1	44			45
nonsense						0
start loss			1			1
frameshift	1	1	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region			1	6		7
non coding			12	20	10	42
Total	1	4	58	43	13

Variants in TPI1

This is a list of pathogenic ClinVar variants found in the TPI1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-6867486-C-T		Triosephosphate isomerase deficiency	Conflicting classifications of pathogenicity (May 01, 2023)
12-6867505-T-G		Triosephosphate isomerase deficiency	Conflicting classifications of pathogenicity (Aug 01, 2024)
12-6867521-G-A		Triosephosphate isomerase deficiency	Benign/Likely benign (Aug 31, 2023)
12-6867524-A-G		Triosephosphate isomerase deficiency	Benign (Nov 30, 2023)
12-6867536-C-T		Triosephosphate isomerase deficiency	Likely benign (Jan 12, 2018)
12-6867538-C-G		Triosephosphate isomerase deficiency	Conflicting classifications of pathogenicity (Jun 01, 2024)
12-6867538-C-T		Triosephosphate isomerase deficiency	Uncertain significance (Jan 12, 2018)
12-6867556-G-A		Triosephosphate isomerase deficiency	Uncertain significance (Aug 06, 2021)
12-6867567-A-G		Triosephosphate isomerase deficiency	Uncertain significance (Apr 01, 2022)
12-6867572-G-T			Likely benign (Oct 30, 2022)
12-6867574-C-T			Uncertain significance (Aug 04, 2023)
12-6867575-C-T			Likely benign (Jul 17, 2018)
12-6867578-C-T			Likely benign (Nov 22, 2022)
12-6867593-TG-T		Triosephosphate isomerase deficiency	Likely pathogenic (Mar 29, 2024)
12-6867593-T-TG		Triosephosphate isomerase deficiency	Pathogenic (Aug 01, 2010)
12-6867603-T-C		Triosephosphate isomerase deficiency	Uncertain significance (May 03, 2022)
12-6867608-G-A			Likely benign (Jan 10, 2023)
12-6867615-G-A			Uncertain significance (Nov 12, 2019)
12-6867629-T-C			Likely benign (Apr 18, 2022)
12-6867639-C-T			Uncertain significance (May 23, 2022)
12-6867645-G-C		Inborn genetic diseases	Uncertain significance (May 21, 2024)
12-6867659-G-C			Likely benign (Mar 01, 2023)
12-6867669-C-G			Uncertain significance (Jul 06, 2022)
12-6867694-C-T			Likely benign (Apr 24, 2022)
12-6867698-G-T			Uncertain significance (Aug 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPI1	protein_coding	protein_coding	ENST00000229270	7	3830

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0302	0.961	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.223	167	159	1.05	0.00000839	1851
Missense in Polyphen		46	52.19	0.8814		703
Synonymous	-1.75	83	65.1	1.28	0.00000388	571
Loss of Function	2.29	5	14.3	0.349	7.16e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000445	0.000394
Ashkenazi Jewish	0.00	0.00
East Asian	0.000113	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000980	0.0000967
Middle Eastern	0.000113	0.000109
South Asian	0.0000999	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Triosephosphate isomerase deficiency (TPID) [MIM:615512]: An autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, progressive neuromuscular dysfunction, susceptibility to bacterial infection, and cardiomyopathy. {ECO:0000269|PubMed:2876430, ECO:0000269|PubMed:8503454, ECO:0000269|PubMed:8571957, ECO:0000269|PubMed:9338582, ECO:0000269|Ref.37}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycolysis / Gluconeogenesis - Homo sapiens (human);Fructose and mannose metabolism - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);Fructose intolerance, hereditary;Glycolysis;Glycogenosis, Type VII. Tarui disease;Gluconeogenesis;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Fanconi-bickel syndrome;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Fructose and Mannose Degradation;Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Fructosuria;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Fatty Acid Beta Oxidation;Cori Cycle;HIF1A and PPARG regulation of glycolysis;Pathways in clear cell renal cell carcinoma;Glycolysis and Gluconeogenesis;Metabolism of carbohydrates;Metabolism;Glycolysis;gluconeogenesis;glycolysis;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Gluconeogenesis;Glucose metabolism;sucrose degradation (Consensus)

Recessive Scores

• pRec: 0.921

Intolerance Scores

• loftool: 0.0957
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.44

Haploinsufficiency Scores

• pHI: 0.0803
• hipred: Y
• hipred_score: 0.775
• ghis: 0.517

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tpi1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; immune system phenotype; hematopoietic system 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); normal phenotype

Gene ontology

• Biological process: gluconeogenesis;glycolytic process;methylglyoxal biosynthetic process;glycerol catabolic process;glyceraldehyde-3-phosphate biosynthetic process;canonical glycolysis
• Cellular component: extracellular space;nucleus;cytosol;extracellular exosome
• Molecular function: triose-phosphate isomerase activity;protein binding;methylglyoxal synthase activity;ubiquitin protein ligase binding;protein homodimerization activity