GGACT

Chr 13

gamma-glutamylamine cyclotransferase

Also known as: A2LD1

NCBI Gene: 87769 ENSG00000134864 UniProt: Q9BVM4 OMIM: 613378

The encoded gamma-glutamylaminecyclotransferase breaks down protein cross-links formed by transglutaminases, specifically catalyzing the conversion of L-gamma-glutamyl-L-epsilon-lysine to 5-oxo-L-proline and contributing to the degradation of crosslinked fibrin. Mutations cause autosomal recessive glutamic aciduria type 3, characterized by elevated urinary glutamic acid levels. This gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene aids in the proteolytic degradation of crosslinked fibrin by breaking down isodipeptide L-gamma-glutamyl-L-epsilon-lysine, a byproduct of fibrin degradation. The reaction catalyzed by the encoded gamma-glutamylaminecyclotransferase produces 5-oxo-L-proline and a free alkylamine. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

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Mechanism

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in GGACT?

gnomAD v4 · ~699k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

264 rare PASS variants

Rare truncating (LoF)

1 in 2,800

52 rare PASS variants

Rare synonymous (reference)

1 in 620

124 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GGACT. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~539k	1 in 340	1 in 3,000
South Asian	~40k	1 in 200	≈ 1 in 8,800
Remaining (unassigned)	~29k	1 in 330	1 in 1,100
European (Finnish)	~24k	1 in 540	none seen
African / African American	~21k	1 in 250	1 in 1,700
East Asian	~18k	1 in 230	≈ 1 in 4,400
Admixed American	~18k	1 in 290	≈ 1 in 8,900
Ashkenazi Jewish	~13k	1 in 1,500	1 in 900
Middle Eastern	~2,849	1 in 220	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓