TPP1

Chr 11AR

tripeptidyl peptidase 1

Also known as: CLN2, GIG1, LPIC, SCAR7, TPP-1

This gene encodes a lysosomal serine protease that cleaves N-terminal tripeptides from substrates and degrades specific neuropeptides and ATP synthase subunits. Mutations cause late-infantile neuronal ceroid lipofuscinosis (CLN2) and autosomal recessive spinocerebellar ataxia type 7 through autosomal recessive inheritance. The pathogenic mechanism involves failure to degrade lysosomal substrates due to loss of protease function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.782 OMIM phenotypes
Clinical SummaryTPP1
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Gene-Disease Validity (ClinGen)
neuronal ceroid lipofuscinosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — TPP1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.000
Z-score 2.48
OE 0.51 (0.340.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.22Z-score
OE missense 1.04 (0.941.14)
321 obs / 310.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.340.78)
00.351.4
Missense OE1.04 (0.941.14)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 15 / 29.5Missense obs/exp: 321 / 310.1Syn Z: -0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTPP1-related neuronal ceroid lipofuscinosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6162th %ile
GOF
0.4678th %ile
LOF
0.3358th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TPP1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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