GGA2
protein-codinggolgi associated, gamma adaptin ear containing, ARF binding protein 2, the group of Golgi associated, gamma adaptin ear containing, ARF binding proteins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GGA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015044.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 108 | 4 | 112 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 119 | 7 | 0 | 126 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055859.1 | 17 | MANE Select | |
| Ensembl | ENSP00000311962.4 | 17 | MANE Select | |
| Ensembl | ENSP00000459414.1 | 4 | Standard | |
| Ensembl | ENSP00000459560.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Lysosome - Homo sapiens (human)
- Vesicle-mediated transport
- TBC/RABGAPs
- Membrane Trafficking
- Metabolism of proteins
Biological Process
- intracellular protein transport
- protein localization to cell surface
- Golgi to plasma membrane protein transport
- cellular protein metabolic process
Molecular Function
- protein binding
- ADP-ribosylation factor binding
Cellular Component
- Golgi apparatus
- trans-Golgi network
- endosome membrane
- clathrin-coated vesicle
- early endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000309859
- Coding exons
- 17
- Length
- 58454
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125747
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.148 | 327 | 335 | 0.977 | 0.0000184 | 3958 |
| Missense (PolyPhen) | 133 | 133.18 | 0.99866 | 1560 | ||
| Synonymous | -0.222 | 136 | 133 | 1.02 | 0.00000777 | 1212 |
| Loss of Function | 2.71 | 17 | 34.0 | 0.500 | 0.00000160 | 398 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00019 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF- dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.834
- RVIS EVS
- -0.98
- RVIS percentile EVS
- 8.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |