TPGS2

Chr 18

tubulin polyglutamylase complex subunit 2

Also known as: C18orf10, HMFN0601, L17, PGs2

This protein is a subunit of the tubulin polyglutamylase complex that mediates polyglutamylation of cilia and flagella, which is essential for their biogenesis and motility. Mutations cause spastic paraplegia 57, an autosomal recessive condition characterized by progressive spasticity primarily affecting the lower limbs. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
46
P/LP submissions
0%
P/LP missense
1.06
LOEUF
Mechanism
Clinical SummaryTPGS2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 43 VUS of 108 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.000
Z-score 1.40
OE 0.59 (0.341.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.03Z-score
OE missense 1.01 (0.891.14)
165 obs / 164.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.59 (0.341.06)
00.351.4
Missense OE1.01 (0.891.14)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 8 / 13.6Missense obs/exp: 165 / 164.0Syn Z: 0.82

ClinVar Variant Classifications

108 submitted variants in ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic3
VUS43
Likely Benign5
Benign1
41
Pathogenic
3
Likely Pathogenic
43
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
41
0
41
Likely Pathogenic
0
0
3
0
3
VUS
0
30
13
0
43
Likely Benign
0
2
2
1
5
Benign
0
0
1
0
1
Total03260193

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

View in ClinVar →

Protein Context — Lollipop Plot

TPGS2 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC