TPI1

Chr 12AR

triosephosphate isomerase 1

Also known as: HEL-S-49, TIM, TPI, TPID

NCBI Gene: 7167ENSG00000111669UniProt: P60174

The protein functions as triosephosphate isomerase, catalyzing the interconversion between dihydroxyacetone phosphate and glyceraldehyde-3-phosphate in glycolysis and gluconeogenesis. Mutations cause triosephosphate isomerase deficiency, which presents as hemolytic anemia and follows autosomal recessive inheritance. This is a severe metabolic disorder that typically manifests in infancy with progressive neurological deterioration in addition to the hematologic features.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Hemolytic anemia due to triosephosphate isomerase deficiencyMIM #615512
AR
0
Active trials
48
Pubs (1 yr)
65
P/LP submissions
9%
P/LP missense
0.73
LOEUF
DN
Mechanism· predicted
Clinical Summary— TPI1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 92 VUS of 242 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — TPI1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.73LOEUF
pLI 0.030
Z-score 2.29
OE 0.35 (0.18–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.22Z-score
OE missense 1.05 (0.93–1.19)
167 obs / 159.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.35 (0.18–0.73)
0≤0.351.4
Missense OE1.05 (0.93–1.19)
0≤0.61.4
Synonymous OE1.28
0≤1.21.6
LoF obs/exp: 5 / 14.3Missense obs/exp: 167 / 159.1Syn Z: -1.75
DN
0.6842th %ile
GOF
0.5170th %ile
LOF
0.3259th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

242 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic7
VUS92
Likely Benign63
Benign12
Conflicting11
50
Pathogenic
7
Likely Pathogenic
92
VUS
63
Likely Benign
12
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
3
45
0
50
Likely Pathogenic
3
2
2
0
7
VUS
2
65
25
0
92
Likely Benign
0
0
34
29
63
Benign
0
0
10
2
12
Conflicting
—11
Total77011631235

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TPI1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Triosephosphate isomerase 1 may be a risk predictor in laryngeal squamous cell carcinoma: a multi-centered study integrating bulk RNA, single-cell RNA, and protein immunohistochemistry
Li JD et al.·Eur J Med Res
2023
TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer progression by stabilizing CDCA5
Jin X et al.·J Transl Med
2022
Systemic Analyses of the Expression of TPI1 and Its Associations with Tumor Microenvironment in Lung Adenocarcinoma and Squamous Cell Carcinoma
Yang X et al.·Dis Markers
2022
miR-1285-3p targets TPI1 to regulate the glycolysis metabolism signaling pathway of Tibetan sheep Sertoli cells
An X et al.·PLoS One
2022
Scalable protein production by Komagataella phaffii enabled by ARS plasmids and carbon source-based selection
Weiss F et al.·Microb Cell Fact
2024
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients