GP2

Chr 16

glycoprotein 2

Also known as: ZAP75

NCBI Gene: 2813 ENSG00000169347 UniProt: P55259 OMIM: 602977

GP2 encodes a GPI-anchored membrane protein that functions as an intestinal M-cell receptor for type I-piliated bacteria, binding pathogens like E. coli and S. typhimurium to facilitate mucosal immune responses. Mutations cause autosomal recessive early-onset inflammatory bowel disease, typically presenting in infancy or early childhood. The gene shows very low constraint against loss-of-function variants (high LOEUF score), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an integral membrane protein that is secreted from intracellular zymogen granules and associates with the plasma membrane via glycosylphosphatidylinositol (GPI) linkage. The encoded protein binds pathogens such as enterobacteria, thereby playing an important role in the innate immune response. The C-terminus of this protein is related to the C-terminus of the protein encoded by the neighboring gene, uromodulin (UMOD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

LOEUF 1.42

Clinical Summary— GP2

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Population Constraint (gnomAD)

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

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ClinVar Variants

77 VUS of 95 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — GP2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score -0.25

OE 1.05 (0.79–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.70Z-score

OE missense 0.89 (0.80–0.98)

274 obs / 308.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.05 (0.79–1.42)

0≤0.351.4

Missense OE?0.89 (0.80–0.98)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 31 / 29.5Missense obs/exp: 274 / 308.4Syn Z: -1.23

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

VUS77

Likely Benign8

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	77	0	77
Likely Benign	7	1	8
Benign	1	3	4
Total	85	4	89

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap GP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →