TGM6

Chr 20AD

transglutaminase 6

Also known as: SCA35, TG6, TGM3L, TGY, dJ734P14.3

NCBI Gene: 343641 ENSG00000166948 UniProt: O95932 OMIM: 613900

The protein catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations cause spinocerebellar ataxia 35, a cerebellar disorder with autosomal dominant inheritance. The gene shows minimal constraint against loss-of-function variants based on population genetics data.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations in this gene are associated with spinocerebellar ataxia type 35 (SCA35). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

OMIM ResearchGenerating clinical summary…

ADLOEUF 1.371 OMIM phenotype

Clinical Summary— TGM6

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 278 VUS of 558 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.82Z-score

OE missense 1.11 (1.03–1.20)

470 obs / 422.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.03 (0.79–1.37)

0≤0.351.4

Missense OE?1.11 (1.03–1.20)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 36 / 34.8Missense obs/exp: 470 / 422.6Syn Z: -0.32

ClinVar Variant Classifications

558 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic7

VUS278

Likely Benign145

Benign76

Conflicting48

Pathogenic

Likely Pathogenic

278

VUS

145

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	0	0	3
Likely Pathogenic	6	1	0	0	7
VUS	25	229	18	6	278
Likely Benign	5	37	31	72	145
Benign	1	12	51	12	76
Conflicting	—				48
Total	39	280	100	90	557

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap TGM6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →