GPA33

Chr 1

glycoprotein A33

Also known as: A33

NCBI Gene: 10223 ENSG00000143167 UniProt: Q99795 OMIM: 602171

The protein is a cell surface glycoprotein containing immunoglobulin superfamily domains that functions in cell-cell recognition and signaling. Mutations cause autosomal recessive congenital diarrhea with prominent failure to thrive in infancy. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

The glycoprotein encoded by this gene is a cell surface antigen that is expressed in greater than 95% of human colon cancers. The open reading frame encodes a 319-amino acid polypeptide having a putative secretory signal sequence and 3 potential glycosylation sites. The predicted mature protein has a 213-amino acid extracellular region, a single transmembrane domain, and a 62-amino acid intracellular tail. The sequence of the extracellular region contains 2 domains characteristic of the CD2 subgroup of the immunoglobulin (Ig) superfamily. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

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 GPA33?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

458 rare PASS variants

Rare truncating (LoF)

1 in 1,300

67 rare PASS variants

Rare synonymous (reference)

1 in 120

188 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPA33. 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)	~556k	1 in 210	1 in 2,300
South Asian	~43k	1 in 85	1 in 670
Remaining (unassigned)	~30k	1 in 85	1 in 840
European (Finnish)	~27k	1 in 200	≈ 1 in 27,000
Admixed American	~22k	1 in 100	1 in 1,900
African / African American	~21k	1 in 120	1 in 1,700
East Asian	~20k	1 in 110	1 in 2,800
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 130	≈ 1 in 720

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓