TPI1
protein-codingtriosephosphate isomerase 1
Gene summary
This gene encodes an enzyme, consisting of two identical proteins, which catalyzes the isomerization of glyceraldehydes 3-phosphate (G3P) and dihydroxy-acetone phosphate (DHAP) in glycolysis and gluconeogenesis. Mutations in this gene are associated with triosephosphate isomerase deficiency. Pseudogenes have been identified on chromosomes 1, 4, 6 and 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014221
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014221
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014221
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Cardiovascular; Hematologic; Neurologic
Intervention: Allergy/Immunology/Infectious; Hematologic
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TPI1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000365.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 32 | 1 | 33 | |||
| missense | 4 | 2 | 62 | 1 | 69 | |
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 2 | 1 | 5 | ||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 7 | 6 | 65 | 33 | 1 | 112 |
Highest pathogenic variant AF is 0.0002533904
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000356.1 | 7 | MANE Select | |
| Ensembl | ENSP00000379933.4 | 7 | MANE Select | |
| RefSeq | NP_001152759.1 | 7 | Standard | |
| RefSeq | NP_001244955.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycolysis / Gluconeogenesis - Homo sapiens (human)
- Fructose and mannose metabolism - Homo sapiens (human)
- Inositol phosphate metabolism - Homo sapiens (human)
- Fructose intolerance, hereditary
- Glycolysis
Biological Process
- gluconeogenesis
- glycolytic process
- methylglyoxal biosynthetic process
- glycerol catabolic process
- glyceraldehyde-3-phosphate biosynthetic process
Molecular Function
- triose-phosphate isomerase activity
- protein binding
- methylglyoxal synthase activity
- ubiquitin protein ligase binding
- protein homodimerization activity
Cellular Component
- extracellular space
- nucleus
- cytosol
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000229270
- Coding exons
- 7
- Length
- 3830
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125748
- p
- 0.0000994
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.223 | 167 | 159 | 1.05 | 0.00000839 | 1851 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00030 | 0.00025 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000098 | 0.000097 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.921
Intolerance Scores
- LoFtool
- 0.0957
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.44
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |