GGA1

Summary

GGA1 (golgi associated, gamma adaptin ear containing, ARF binding protein 1, HGNC:17842) is a protein-coding gene on chromosome 22q13.1, encoding ADP-ribosylation factor-binding protein GGA1 (Q9UJY5). Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes.

This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) protein family. Members of this family are 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. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 26088 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 117 total
• MANE Select transcript: NM_013365

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17842
Approved symbol	GGA1
Name	golgi associated, gamma adaptin ear containing, ARF binding protein 1
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100083
Ensembl biotype	protein_coding
OMIM	606004
Entrez	26088

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 29 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000325180, ENST00000326597, ENST00000343632, ENST00000381756, ENST00000405147, ENST00000406772, ENST00000411501, ENST00000413251, ENST00000423024, ENST00000429218, ENST00000431745, ENST00000439161, ENST00000447515, ENST00000449944, ENST00000453208, ENST00000460957, ENST00000463672, ENST00000475445, ENST00000481613, ENST00000484804, ENST00000488672, ENST00000489772, ENST00000491295, ENST00000715689, ENST00000851283, ENST00000851284, ENST00000851285, ENST00000851286, ENST00000851287, ENST00000851288, ENST00000937679, ENST00000937680, ENST00000937681, ENST00000957660, ENST00000957661, ENST00000957662, ENST00000957663

RefSeq mRNA: 5 — MANE Select: NM_013365 NM_001001560, NM_001172687, NM_001172688, NM_001363771, NM_013365

CCDS: CCDS13951, CCDS33643, CCDS54526, CCDS87022

Canonical transcript exons

ENST00000343632 — 17 exons

Exon	Start	End
ENSE00000653938	37625797	37625949
ENSE00000653945	37629998	37630170
ENSE00000653946	37630903	37631099
ENSE00000880168	37620238	37620361
ENSE00000880169	37620813	37620913
ENSE00000880174	37623552	37623633
ENSE00001286815	37624969	37625076
ENSE00001823052	37632601	37633564
ENSE00003495641	37616922	37616997
ENSE00003506106	37631996	37632165
ENSE00003525463	37629462	37629526
ENSE00003581981	37618448	37618546
ENSE00003602962	37621616	37621696
ENSE00003662687	37614190	37614274
ENSE00003683548	37623327	37623467
ENSE00003686005	37632405	37632515
ENSE00004027586	37608834	37608903

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6706 / max 567.6905, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192157	10.2621	1785
192159	6.4823	1723
192155	3.3294	1422
192160	0.7686	215
192156	0.4651	130
192158	0.3630	159

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	99.58	gold quality
left testis	UBERON:0004533	99.21	gold quality
right testis	UBERON:0004534	99.18	gold quality
cervix squamous epithelium	UBERON:0006922	98.58	gold quality
endothelial cell	CL:0000115	98.38	gold quality
right uterine tube	UBERON:0001302	97.29	gold quality
ileal mucosa	UBERON:0000331	97.08	gold quality
testis	UBERON:0000473	96.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.64	gold quality
pituitary gland	UBERON:0000007	96.55	gold quality
cerebellar hemisphere	UBERON:0002245	96.41	gold quality
gingival epithelium	UBERON:0001949	96.37	gold quality
cerebellar cortex	UBERON:0002129	96.37	gold quality
adenohypophysis	UBERON:0002196	96.25	gold quality
right lobe of thyroid gland	UBERON:0001119	96.08	gold quality
right adrenal gland cortex	UBERON:0035827	95.98	gold quality
lower esophagus mucosa	UBERON:0035834	95.98	gold quality
cerebellum	UBERON:0002037	95.97	gold quality
right adrenal gland	UBERON:0001233	95.95	gold quality
tibialis anterior	UBERON:0001385	95.92	gold quality
left ovary	UBERON:0002119	95.92	gold quality
left lobe of thyroid gland	UBERON:0001120	95.90	gold quality
left adrenal gland cortex	UBERON:0035825	95.78	gold quality
spleen	UBERON:0002106	95.73	gold quality
right ovary	UBERON:0002118	95.68	gold quality
parotid gland	UBERON:0001831	95.67	gold quality
adrenal cortex	UBERON:0001235	95.62	gold quality
thyroid gland	UBERON:0002046	95.56	gold quality
left adrenal gland	UBERON:0001234	95.55	gold quality
metanephros cortex	UBERON:0010533	95.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting GGA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-6895-5P	97.05	64.96	522
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-4749-3P	96.40	66.24	798
HSA-MIR-3918	96.13	64.65	1300

Literature-anchored findings (GeneRIF, showing 24)

• X-ray structure of the GGA1 VHS domain alone, and in complex with the carboxy-terminal peptide of cation-independent mannose 6-phosphate receptor containing an ACLL sequence (PMID:11859376)
• endocytosis and intracellular transport of memapsin 2, mediated by its cytosolic domain, may involve the binding of GGA1 and GGA2 (PMID:12135764)
• The 2.4-A crystal structure of the GAT domain of human GGA1 reveals a three-helix bundle, with a long N-terminal helical extension that is not conserved in GAT domains that do not bind ARF. (PMID:12668765)
• X-ray crystal structures of the human GGA1-GAT domain and the complex between ARF1-GTP and the N-terminal region of the GAT domain (PMID:12679809)
• Crystal structure of the human GGA1 GAT domain (PMID:12767220)
• A hydrophobic surface patch on the C-terminal three-helix bundle motif of the GGA1 GAT domain is directly involved in binding with a coiled-coil region of rabaptin-5. (PMID:14636058)
• GGA1 interacts with the adaptor protein AP-1 through a WNSF sequence in its hinge region (PMID:14973137)
• Rabaptin-5, ubiquitin, and TSG101 bind to overlapping but distinct binding sites on the trihelical bundle subdomain of GGA-1 protein (PMID:15143060)
• serine phosphorylation of BACE is a physiologically relevant post-translational modification that regulates trafficking in the juxtanuclear compartment by interaction with GGA1 (PMID:15466887)
• GGA proteins funstion with the phosphorylated ACDL in the memasin 2-recycling pathway from endosomes to trans Golgi on the way back to the cell surface. (PMID:15615712)
• Our data indicate that GGA proteins are not only involved in the sorting at the TGN but also mediate the retrograde transport of cargo proteins from endosomes to the TGN. (PMID:15886016)
• the trafficking of adiponectin through its secretory pathway is dependent on GGA-coated vesicles (PMID:16407204)
• GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. (PMID:17005855)
• GGA1 alters the proteolytic processing of beta-amyloid precursor protein (APP) and the secretion of APPs and amyloid-beta, suggesting a role of GGA1 in Alzheimer’s disease pathogenesis. (PMID:17151287)
• These results show that the dual roles of PI4P can promote specific GGA targeting and cargo recognition at the trans-Golgi network. (PMID:17494868)
• the interaction between the hinge region and the GAE domain underlies the autoregulation of GGA function in clathrin-mediated trafficking through competing with the accessory proteins and the AP-1 complex (PMID:17506864)
• p56 tightly cooperates with the GGAs in the sorting of cathepsin D to lysosomes, probably by enabling the movement of GGA-containing transport carriers. (PMID:17596511)
• GGA overexpression causes various sorting defects as measured by recycling of CD-MPR, internalization of transferrin receptor, and the subcellular localization of proteins like Tsg101, ubiquitin, and Hrs. (PMID:19788741)
• On basis of these results, propose that GGA1 facilitates LR11 endocytic traffic and that LR11 modulates A-beta levels by promoting amyloid-beta precursor protein traffic to the endocytic recycling compartment (PMID:22621900)
• These data indicate that clathrin is required for the function of AP-1- and GGA-coated carriers at the trans-Golgi network but may be dispensable for outward traffic en route to the plasma membrane. (PMID:24407285)
• These findings show that the AD-like phenotype of NPC model cells can be partly reverted by promoting a non-amyloidogenic processing of APP through the upregulation of GGA1 supporting its preventive role against AD (PMID:24866237)
• full length alpha2B-AR associated with GGA2 but not GGA1, its third intracellular loop was found to directly interact with both GGA1 and GGA2. More interestingly, further mapping of interaction domains showed that the GGA1 hinge region and the GGA2 GAE domain bound to multiple subdomains of the loop. (PMID:27901063)
• The adaptor, GGA1, and retromer are essential to mediate rapid trafficking of phosphorylated BACE1 to recycling endosomes. Therefore, post-translational phosphorylation of DISLL enhances the exit of BACE1 from early endosomes, a pathway mediated by GGA1 and retromer, which is important in regulating amyloid beta production. (PMID:29142073)
• Inactivation of the three GGA genes in HeLa cells partially compromises lysosomal enzyme sorting. (PMID:33206455)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	gga1	ENSDARG00000038537
mus_musculus	Gga1	ENSMUSG00000033128
rattus_norvegicus	Gga1	ENSRNOG00000008897
drosophila_melanogaster	Stam	FBGN0027363
drosophila_melanogaster	Gga	FBGN0030141
drosophila_melanogaster	Wdfy2	FBGN0032246
caenorhabditis_elegans	stam-1	WBGENE00004109
caenorhabditis_elegans		WBGENE00008402

Paralogs (10): WDFY1 (ENSG00000085449), TOM1 (ENSG00000100284), GGA2 (ENSG00000103365), STAM2 (ENSG00000115145), GGA3 (ENSG00000125447), STAM (ENSG00000136738), WDFY2 (ENSG00000139668), TOM1L1 (ENSG00000141198), TOM1L2 (ENSG00000175662), HGS (ENSG00000185359)

Protein

Protein identifiers

ADP-ribosylation factor-binding protein GGA1 — Q9UJY5 (reviewed: Q9UJY5)

Alternative names: Gamma-adaptin-related protein 1, Golgi-localized, gamma ear-containing, ARF-binding protein 1

All UniProt accessions (10): B0QYR5, B0QYR6, B0QYR8, B0QYR9, B0QYS0, B0QYS1, B0QYS2, B0QYS3, B0QYS5, Q9UJY5

UniProt curated annotations — full annotation on UniProt →

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 (DXXLL) motif. Mediates export of the GPCR receptor ADRA2B to the cell surface. Required for targeting PKD1:PKD2 complex from the trans-Golgi network to the cilium membrane. Regulates retrograde transport of proteins such as phosphorylated form of BACE1 from endosomes to the trans-Golgi network.

Subunit / interactions. Monomer. Interacts with GGA2 and GGA3. Binds to clathrin and activated ARFs, including ARF1, ARF5 and ARF6. Interacts with RABEP1. Interacts with RABGEF1. Interacts with the type-I membrane proteins LRP3, M6PR/CD-MPR and IGF2R/CI-MPR. Interacts (via N-terminal VHS domain) with SORL1/sorLA and SORT1 (via C-terminal cytosolic domain). Interacts with EPN4. Interacts with CCDC91. Interacts with HEATR5B/p200a. Interacts with SYNRG/gamma-synergin. Interacts (via GAE doamin) with NECAP1 and NECAP2. Interacts (via GAE domain) with AFTPH/aftiphilin. Interacts with TSG101 and UBC. Interacts with RNF11. Interacts (via VHS domain) with BACE1 (via DXXLL motif); the interaction highly increases when BACE1 is phosphorylated at ‘Ser-498’. Interacts with CNST. Interacts with ADRA2B. Interacts with ARL3; the interaction recruits, in collaboration with RABEP1, PKD1:PKD2 complex to trans-Golgi network and is required for ciliary targeting.

Subcellular location. Golgi apparatus. trans-Golgi network membrane. Endosome membrane. Early endosome membrane.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylated by CK2 and dephosphorylated by PP2A. Phosphorylation of GGA1 allows the internal DXXLL motif to bind the VHS domain and to inhibit the recognition of cargo signals. Ubiquitinated.

Domain organisation. The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (DXXLL motif). The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis. The unstructured hinge region contains clathrin-binding but no autoinhibitory (DXXLL) motifs. The GAE domain binds accessory proteins regulating GGAs function.

Similarity. Belongs to the GGA protein family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UJY5-1	1	yes
Q9UJY5-2	2
Q9UJY5-3	3
Q9UJY5-4	4
Q9UJY5-5	5
Q9UJY5-6	6

RefSeq proteins (5): NP_001001560, NP_001166158, NP_001166159, NP_001350700, NP_037497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002014	VHS_dom	Domain
IPR004152	GAT_dom	Domain
IPR008152	Clathrin_a/b/g-adaptin_app_Ig	Domain
IPR008153	GAE_dom	Domain
IPR008942	ENTH_VHS	Homologous_superfamily
IPR013041	Clathrin_app_Ig-like_sf	Homologous_superfamily
IPR027422	GGA1-3	Family
IPR038425	GAT_sf	Homologous_superfamily
IPR041198	GGA_N-GAT	Domain

Pfam: PF00790, PF02883, PF03127, PF18308

UniProt features (81 total): mutagenesis site 25, helix 19, strand 10, splice variant 6, modified residue 4, region of interest 4, domain 3, compositionally biased region 3, turn 3, sequence variant 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
1J2J	X-RAY DIFFRACTION	1.6
3G2S	X-RAY DIFFRACTION	1.7
1UJK	X-RAY DIFFRACTION	1.9
1JWG	X-RAY DIFFRACTION	2
3G2T	X-RAY DIFFRACTION	2
1JWF	X-RAY DIFFRACTION	2.1
1O3X	X-RAY DIFFRACTION	2.1
3G2V	X-RAY DIFFRACTION	2.1
1NA8	X-RAY DIFFRACTION	2.3
2DWY	X-RAY DIFFRACTION	2.3
3G2U	X-RAY DIFFRACTION	2.3
1NWM	X-RAY DIFFRACTION	2.4
3G2W	X-RAY DIFFRACTION	2.4
1X79	X-RAY DIFFRACTION	2.41
1OM9	X-RAY DIFFRACTION	2.5
2DWX	X-RAY DIFFRACTION	2.55
1PY1	X-RAY DIFFRACTION	2.6
1UJJ	X-RAY DIFFRACTION	2.6
1NAF	X-RAY DIFFRACTION	2.8
1OXZ	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJY5-F1	74.62	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 1, 185, 355, 418

Mutagenesis-validated functional residues (25):

Position	Phenotype
92	abolishes interaction with igf2r.
182	abolishes interaction with arf1, ubc and tsg101.
194	abolishes interaction with arf1 and rabep1.
197	abolishes interaction with arf1, ubc and tsg101.
198	abolishes interaction with arf1.
200	abolishes interaction with arf1.
204	abolishes interaction with arf1.
259	abolishes interaction with rabep1.
260	no effect on interaction with rabep1.
260	abolishes interaction with rabep1 and ubc.
264	abolishes interaction with rabep1.
267	abolishes interaction with rabep1 and ubc.
277	abolishes interaction with rabep1, ubc and tsg101.
281	abolishes interaction with rabep1.
284	abolishes interaction with rabep1.
355	increased interaction with igf2r. reduced phosphorylation. no effect on the interaction with sorl1.
355	abolishes interaction with igf2r. no effect on the interaction with sorl1.
356–360	partial loss of clathrin-binding.
358	increased interaction with igf2r.
361–362	increased interaction with igf2r.
563	abolishes interaction with ccdc91.
564	abolishes interaction with ccdc91.
570	abolishes interaction with ccdc91.
572	abolishes interaction with ccdc91.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8854214	TBC/RABGAPs
R-HSA-977225	Amyloid fiber formation

MSigDB gene sets: 0 (showing top):

GO Biological Process (11): intracellular protein transport (GO:0006886), Golgi to plasma membrane transport (GO:0006893), intracellular protein localization (GO:0008104), protein catabolic process (GO:0030163), protein localization to cell surface (GO:0034394), retrograde transport, endosome to Golgi (GO:0042147), Golgi to plasma membrane protein transport (GO:0043001), positive regulation of protein catabolic process (GO:0045732), protein localization to ciliary membrane (GO:1903441), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (4): small GTPase binding (GO:0031267), phosphatidylinositol binding (GO:0035091), ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (10): nucleoplasm (GO:0005654), early endosome (GO:0005769), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), endosome membrane (GO:0010008), membrane (GO:0016020), early endosome membrane (GO:0031901), protein-containing complex (GO:0032991), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Rab regulation of trafficking	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular protein localization	3
cellular anatomical structure	3
protein transport	2
transport	2
endosome	2
cytoplasm	2
endomembrane system	2
intracellular transport	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
macromolecule localization	1
macromolecule catabolic process	1
protein metabolic process	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
Golgi to plasma membrane transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
protein localization to cilium	1
protein localization to membrane	1
protein localization to cell periphery	1
establishment of protein localization	1
cellular process	1
GTPase binding	1
anion binding	1
ubiquitin-like protein binding	1
binding	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
early endosome	1
endosome membrane	1
cellular_component	1

Protein interactions and networks

STRING

1409 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGA1	RABEP1	Q15276	960
GGA1	IGF2R	P11717	947
GGA1	M6PR	P20645	921
GGA1	ARF1	P10947	885
GGA1	GOLPH3	Q9H4A6	783
GGA1	CSNK2A2	P19784	763
GGA1	CNST	Q6PJW8	763
GGA1	CSNK2A1	P19138	761
GGA1	RABGEF1	Q9UJ41	734
GGA1	AP1M1	Q9BXS5	733
GGA1	SORT1	Q99523	729
GGA1	SYNRG	Q9UMZ2	703
GGA1	BACE1	P56817	700
GGA1	SORL1	Q92673	699
GGA1	AP1S1	P61966	696

IntAct

139 interactions, top by confidence:

A	B	Type	Score
GGA1	RABEP1	psi-mi:“MI:0407”(direct interaction)	0.840
RABEP1	GGA1	psi-mi:“MI:0407”(direct interaction)	0.840
GGA1	RABEP1	psi-mi:“MI:0915”(physical association)	0.840
RABEP1	GGA1	psi-mi:“MI:0915”(physical association)	0.840
IGF2R	GGA1	psi-mi:“MI:0407”(direct interaction)	0.830
GGA1	IGF2R	psi-mi:“MI:0407”(direct interaction)	0.830
GGA1	IGF2R	psi-mi:“MI:0915”(physical association)	0.830
IGF2R	GGA1	psi-mi:“MI:0915”(physical association)	0.830
RNF11	GGA1	psi-mi:“MI:0407”(direct interaction)	0.800
GGA1	RNF11	psi-mi:“MI:0407”(direct interaction)	0.800
GGA1	RNF11	psi-mi:“MI:0915”(physical association)	0.800
PSMD4	PSMD11	psi-mi:“MI:0914”(association)	0.750
SORL1	GGA1	psi-mi:“MI:0915”(physical association)	0.740
GGA1	GGA2	psi-mi:“MI:0407”(direct interaction)	0.740
GGA2	GGA1	psi-mi:“MI:0407”(direct interaction)	0.740
GGA1	GGA2	psi-mi:“MI:0403”(colocalization)	0.740
GGA1	GGA2	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (244): RNF11 (Affinity Capture-Western), RNF11 (Reconstituted Complex), RNF11 (Protein-peptide), ARF1 (Reconstituted Complex), ARF3 (Reconstituted Complex), ARF5 (Reconstituted Complex), ARF6 (Reconstituted Complex), GGA1 (Two-hybrid), C1orf216 (Two-hybrid), UBC (Reconstituted Complex), TOLLIP (Reconstituted Complex), GGA1 (Affinity Capture-Western), DHX15 (Co-fractionation), EIF4EBP1 (Co-fractionation), GGA1 (Co-fractionation)

ESM2 similar proteins: A0A0G2JV04, B0V207, D3Z8X7, D3ZFJ3, D3ZND0, F1LM81, G9CGD6, O00499, O08539, O08839, O12940, O60308, O60784, O75674, O88746, P42567, P55194, Q05DH4, Q0GNC1, Q0IHV1, Q27J81, Q3B7M3, Q3UN70, Q4KLN4, Q505K2, Q5FVK6, Q5T0F9, Q5U3K5, Q66HA5, Q68EF0, Q6P1N0, Q6P5E6, Q6P9Q4, Q6P9Q6, Q80V31, Q80V94, Q8BMI3, Q8BRN9, Q8K1A6, Q8R0H9

Diamond homologs: A0A0G2JV04, A3LXQ8, F4KAU9, O01498, O14964, O43747, O60784, O75843, O75886, O88512, O88746, O93436, P22892, P70297, Q0V8S0, Q5R5M2, Q68FJ8, Q6P5E6, Q8BMI3, Q8R0H9, Q92783, Q960X8, Q99LI8, Q9JJ50, Q9NZ52, Q9UJY4, Q9UJY5, A0JNJ1, A6QLK6, A7A261, E9Q634, O13154, O35179, O35180, O35964, O42287, O75791, O88811, O89100, O97902

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CSNK2A1	“down-regulates activity”	GGA1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TBC/RABGAPs	5	25.9×	2e-04
trans-Golgi Network Vesicle Budding	5	25.4×	2e-04
Golgi Associated Vesicle Biogenesis	6	24.0×	5e-05
Signaling by ALK fusions and activated point mutants	6	18.0×	2e-04
Cargo recognition for clathrin-mediated endocytosis	7	14.7×	1e-04
Clathrin-mediated endocytosis	8	13.6×	5e-05
G2/M Checkpoints	5	13.4×	3e-03
Amyloid fiber formation	5	10.3×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting to lysosome	5	48.8×	4e-05
receptor-mediated endocytosis	6	20.8×	2e-04
endocytosis	6	8.9×	6e-03
intracellular protein transport	7	7.1×	6e-03
negative regulation of cell population proliferation	9	5.9×	4e-03
protein transport	8	5.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

117 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3259 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37608904:G:GG	donor_gain	1.0000
22:37614188:A:AG	acceptor_gain	1.0000
22:37614189:G:GG	acceptor_gain	1.0000
22:37614189:GATA:G	acceptor_gain	1.0000
22:37614264:G:GT	donor_gain	1.0000
22:37614270:GAGGG:G	donor_gain	1.0000
22:37614271:AGGG:A	donor_gain	1.0000
22:37614272:GGG:G	donor_gain	1.0000
22:37614272:GGGG:G	donor_gain	1.0000
22:37614273:GG:G	donor_gain	1.0000
22:37614273:GGG:G	donor_gain	1.0000
22:37614274:GG:G	donor_gain	1.0000
22:37614275:G:GG	donor_gain	1.0000
22:37614275:GT:G	donor_loss	1.0000
22:37614276:T:G	donor_loss	1.0000
22:37617007:G:T	donor_gain	1.0000
22:37618443:CACA:C	acceptor_loss	1.0000
22:37618445:CA:C	acceptor_loss	1.0000
22:37618446:A:AG	acceptor_gain	1.0000
22:37618447:G:GG	acceptor_gain	1.0000
22:37618447:GGT:G	acceptor_gain	1.0000
22:37618544:AAG:A	donor_loss	1.0000
22:37618546:GG:G	donor_loss	1.0000
22:37618547:G:GA	donor_loss	1.0000
22:37618548:T:A	donor_loss	1.0000
22:37620233:T:TA	acceptor_gain	1.0000
22:37620235:AAG:A	acceptor_loss	1.0000
22:37620236:A:AG	acceptor_gain	1.0000
22:37620236:A:AT	acceptor_loss	1.0000
22:37620237:G:GC	acceptor_gain	1.0000

AlphaMissense

4179 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37618505:T:C	F88L	1.000
22:37618507:C:A	F88L	1.000
22:37618507:C:G	F88L	1.000
22:37618519:C:A	N92K	1.000
22:37618519:C:G	N92K	1.000
22:37618529:A:G	K96E	1.000
22:37618531:G:C	K96N	1.000
22:37618531:G:T	K96N	1.000
22:37620298:T:A	W122R	1.000
22:37620298:T:C	W122R	1.000
22:37620350:T:C	L139P	1.000
22:37621629:T:C	L181P	1.000
22:37621632:T:C	L182P	1.000
22:37621664:G:C	A193P	1.000
22:37621665:C:A	A193D	1.000
22:37621674:T:C	L196P	1.000
22:37621677:T:A	I197N	1.000
22:37621677:T:C	I197T	1.000
22:37621677:T:G	I197S	1.000
22:37623400:T:C	L228P	1.000
22:37623589:T:A	L263H	1.000
22:37623589:T:C	L263P	1.000
22:37623591:T:C	F264L	1.000
22:37623593:C:A	F264L	1.000
22:37623593:C:G	F264L	1.000
22:37623598:T:C	L266P	1.000
22:37623601:C:A	A267E	1.000
22:37624978:T:C	L281P	1.000
22:37624983:G:C	A283P	1.000
22:37624996:T:A	L287H	1.000

dbSNP variants (sampled 300 via entrez): RS1000122470 (22:37624649 T>C), RS1000175141 (22:37607516 C>A,T), RS1000281879 (22:37608866 G>A,C,T), RS1000383286 (22:37617141 C>T), RS1000435980 (22:37614359 C>A,T), RS1000475892 (22:37631498 G>A), RS1000696231 (22:37628069 C>A), RS1000778259 (22:37631772 G>A), RS1000803912 (22:37614744 C>T), RS1000807683 (22:37608059 TG>T), RS1000809510 (22:37634028 C>G), RS1000905005 (22:37633798 G>A), RS1000917170 (22:37610031 G>A,C), RS1001547276 (22:37610768 C>G,T), RS1001570927 (22:37631472 C>A,T)

Disease associations

OMIM: gene MIM:606004 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008513_38	Health literacy	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010104	health literacy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, affects methylation, increases abundance, increases expression	2
Silicon Dioxide	increases expression, decreases methylation	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
hydroxyhydroquinone	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
chloropicrin	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases expression, affects cotreatment	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Fulvestrant	increases methylation	1
Benzene	increases expression	1
Cadmium	increases expression, increases abundance	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Gallic Acid	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Particulate Matter	affects expression, affects methylation, increases abundance	1

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1B6	HeLa GGA1-/-	Cancer cell line	Female
CVCL_F1BA	HeLa GGA123-/-	Cancer cell line	Female
CVCL_SP91	HAP1 GGA1 (-) 1	Cancer cell line	Male
CVCL_SP92	HAP1 GGA1 (-) 2	Cancer cell line	Male
CVCL_SP93	HAP1 GGA1 (-) 3	Cancer cell line	Male
CVCL_SP94	HAP1 GGA1 (-) 4	Cancer cell line	Male
CVCL_SP95	HAP1 GGA1 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.