TGM6

Chr 20AD

transglutaminase 6

ENSG00000166948UniProt: O95932

Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 35MIM #613908
AD
484
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TGM6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 245 VUS of 484 total submissions
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.37LOEUF
pLI 0.000
Z-score -0.19
OE 1.03 (0.79–1.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.82Z-score
OE missense 1.11 (1.03–1.20)
470 obs / 422.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.03 (0.79–1.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.03–1.20)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 36 / 34.8Missense obs/exp: 470 / 422.6Syn Z: -0.32

ClinVar Variant Classifications

484 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic6
VUS245
Likely Benign115
Benign66
Conflicting28
24
Pathogenic
6
Likely Pathogenic
245
VUS
115
Likely Benign
66
Benign
28
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
21
0
24
Likely Pathogenic
2
0
4
0
6
VUS
19
198
24
4
245
Likely Benign
2
25
32
56
115
Benign
0
8
49
9
66
Conflicting
—28
Total2523213069484

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

View in ClinVar →

Protein Context — Lollipop Plot

TGM6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TRANSGLUTAMINASE 6; TGM6
MIM #613900 · *

Spinocerebellar ataxia 35

MIM #613908

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TGM6 variants in Parkinson's disease: clinical findings and functional evidence.
Chen K et al.·J Integr Neurosci
2020Functional
Spinocerebellar ataxia 35: novel mutations in TGM6 with clinical and genetic characterization.
Guo YC et al.·Neurology
2014
Cytokines from parasites: manipulating host responses by molecular mimicry.
Maizels RM et al.·Biochem J
2025Review
Genetics of dizziness: cerebellar and vestibular disorders.
Requena T et al.·Curr Opin Neurol
2014Review
TGM6 might not be a specific causative gene for spinocerebellar ataxia resulting from genetic analysis and functional study.
Cheng HL et al.·Gene
2021Functional
A significant inflation in TGM6 genetic risk casts doubt in its causation in spinocerebellar ataxia type 35.
Fung JLF et al.·Parkinsonism Relat Disord
2019
Genetic Variants Associated with Episodic Ataxia in Korea.
Choi KD et al.·Sci Rep
2017
Positional cloning and next-generation sequencing identified a TGM6 mutation in a large Chinese pedigree with acute myeloid leukaemia.
Pan LL et al.·Eur J Hum Genet
2015
Recent advances in the genetics of cerebellar ataxias.
Sailer A et al.·Curr Neurol Neurosci Rep
2012Review
TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing.
Wang JL et al.·Brain
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools