TPP1

Chr 11AR

tripeptidyl peptidase 1

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

NCBI Gene: 1200ENSG00000166340UniProt: O14773OMIM: 607998

This gene encodes a member of the sedolisin family of serine proteases. The protease functions in the lysosome to cleave N-terminal tripeptides from substrates, and has weaker endopeptidase activity. It is synthesized as a catalytically-inactive enzyme which is activated and auto-proteolyzed upon acidification. Mutations in this gene result in late-infantile neuronal ceroid lipofuscinosis, which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ceroid lipofuscinosis, neuronal, 2MIM #204500
AR
Spinocerebellar ataxia, autosomal recessive 7MIM #609270
AR

Clinical highlights

Management implications
TPP1 has an approved disease-modifying therapy
Gene-disease validity (ClinGen)
neuronal ceroid lipofuscinosis · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
4
Active trials
60
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.78
LOEUF
LOF
Mechanism· G2P
  • cerliponase alfa (Brineura)
    enzyme replacementApproved · FDA 2017

    Recombinant human TPP1 enzyme replacement.

    Delivery: Intracerebroventricular, every 2 weeksEligibility: ≥3 yr with CLN2

    Slows motor/language decline

Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.

ClinicalTrials.gov

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.78LOEUF
pLI 0.000
Z-score 2.48
OE 0.51 (0.34–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.22Z-score
OE missense 1.04 (0.94–1.14)
321 obs / 310.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.51 (0.34–0.78)
0≤0.351.4
Missense OE?1.04 (0.94–1.14)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
LoF obs/exp: 15 / 29.5Missense obs/exp: 321 / 310.1Syn Z: -0.16

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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