GGA2

Chr 16

golgi associated, gamma adaptin ear containing, ARF binding protein 2

Also known as: VEAR

NCBI Gene: 23062ENSG00000103365UniProt: Q9UJY4

This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. This family member may play a significant role in cargo molecules regulation and clathrin-coated vesicle assembly. [provided by RefSeq, Jul 2008]

215
ClinVar variants
30
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GGA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 132 VUS of 215 total submissions

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.
0.75LOEUF
pLI 0.000
Z-score 2.71
OE 0.50 (0.34–0.75)
Tolerant

Typical tolerance to LoF variation

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.
0.15Z-score
OE missense 0.98 (0.89–1.07)
327 obs / 334.6 exp
Tolerant

Mild missense constraint

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.0.50 (0.34–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.89–1.07)
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.1.02
0≤1.21.6
LoF obs/exp: 17 / 34.0Missense obs/exp: 327 / 334.6Syn Z: -0.22

ClinVar Variant Classifications

215 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic3
VUS132
Likely Benign13
Benign13
27
Pathogenic
3
Likely Pathogenic
132
VUS
13
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
3
0
3
VUS
0
104
28
0
132
Likely Benign
0
4
6
3
13
Benign
0
0
13
0
13
Total0108773188

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

View in ClinVar →

Protein Context — Lollipop Plot

GGA2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sinonasal adenosquamous carcinomas arising in seromucinous hamartoma or respiratory epithelial adenomatoid hamartoma with atypical features: Report of five detailed clinicopathological and molecular characterisation of rare entity.
Bradová M et al.·Histopathology
2025
A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome.
Hirst J et al.·J Cell Biol
2000
Association of SNP rs80659072 in the ZRS with polydactyly in Beijing You chickens.
Chu Q et al.·PLoS One
2017
Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Munster AML-study group.
Coenen EA et al.·Blood
2013
Glycine-extended gastrin induces matrix metalloproteinase-1- and -3-mediated invasion of human colon cancer cells through type I collagen gel and Matrigel.
Baba M et al.·Int J Cancer
2004
Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors.
Wood O et al.·Oncotarget
2016
A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.
Zhu L et al.·Proc Natl Acad Sci U S A
1996
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