GORASP1

Summary

GORASP1 (golgi reassembly stacking protein 1, HGNC:16769) is a protein-coding gene on chromosome 3p22.2, encoding Golgi reassembly-stacking protein 1 (Q9BQQ3). Key structural protein of the Golgi apparatus.

The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a membrane protein involved in establishing the stacked structure of the Golgi apparatus. It is a caspase-3 substrate, and cleavage of this encoded protein contributes to Golgi fragmentation in apoptosis. This encoded protein can form a complex with the Golgi matrix protein GOLGA2, and this complex binds to the vesicle docking protein p115. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 64689 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_031899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16769
Approved symbol	GORASP1
Name	golgi reassembly stacking protein 1
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	GRASP65, P65, FLJ23443
Ensembl gene	ENSG00000114745
Ensembl biotype	protein_coding
OMIM	606867
Entrez	64689

Gene structure

Transcript identifiers

Ensembl transcripts: 79 — 37 protein_coding, 26 retained_intron, 13 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000319283, ENST00000411813, ENST00000413243, ENST00000416741, ENST00000419156, ENST00000422110, ENST00000427459, ENST00000431601, ENST00000437458, ENST00000441081, ENST00000441302, ENST00000452389, ENST00000453680, ENST00000466443, ENST00000469471, ENST00000470910, ENST00000473827, ENST00000476334, ENST00000479124, ENST00000479927, ENST00000486133, ENST00000488479, ENST00000489587, ENST00000492064, ENST00000493751, ENST00000493938, ENST00000695397, ENST00000695412, ENST00000695414, ENST00000695415, ENST00000695416, ENST00000695417, ENST00000695424, ENST00000695425, ENST00000695426, ENST00000695427, ENST00000695428, ENST00000695429, ENST00000695430, ENST00000695431, ENST00000695441, ENST00000695442, ENST00000695443, ENST00000695444, ENST00000695445, ENST00000695446, ENST00000695587, ENST00000695588, ENST00000695589, ENST00000695590, ENST00000695591, ENST00000695592, ENST00000695593, ENST00000695594, ENST00000695595, ENST00000695596, ENST00000695597, ENST00000695613, ENST00000881996, ENST00000881997, ENST00000881998, ENST00000881999, ENST00000882000, ENST00000882001, ENST00000882002, ENST00000882003, ENST00000882004, ENST00000882005, ENST00000925759, ENST00000925760, ENST00000925761, ENST00000925762, ENST00000957144, ENST00000957145, ENST00000957146, ENST00000957147, ENST00000957148, ENST00000957149, ENST00000957150

RefSeq mRNA: 5 — MANE Select: NM_031899 NM_001278789, NM_001278790, NM_001410726, NM_001410731, NM_031899

CCDS: CCDS2681, CCDS63596, CCDS63597, CCDS93245, CCDS93246

Canonical transcript exons

ENST00000319283 — 9 exons

Exon	Start	End
ENSE00002322809	39107479	39107627
ENSE00003458359	39102678	39102881
ENSE00003459369	39101016	39101102
ENSE00003465466	39100305	39100503
ENSE00003479339	39098741	39098893
ENSE00003543781	39103473	39103553
ENSE00003560473	39100747	39100877
ENSE00003634549	39099353	39099503
ENSE00003657015	39096599	39098489

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2386 / max 125.0914, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41723	14.0121	1810
41722	1.2265	840

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	96.64	gold quality
right uterine tube	UBERON:0001302	96.43	gold quality
transverse colon	UBERON:0001157	96.12	gold quality
minor salivary gland	UBERON:0001830	96.11	gold quality
body of pancreas	UBERON:0001150	96.08	gold quality
left lobe of thyroid gland	UBERON:0001120	95.81	gold quality
body of stomach	UBERON:0001161	95.76	gold quality
right lung	UBERON:0002167	95.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.60	gold quality
rectum	UBERON:0001052	95.57	gold quality
body of uterus	UBERON:0009853	95.49	gold quality
metanephros cortex	UBERON:0010533	95.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.39	gold quality
lower esophagus	UBERON:0013473	95.37	gold quality
left uterine tube	UBERON:0001303	95.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.03	gold quality
thyroid gland	UBERON:0002046	94.90	gold quality
right coronary artery	UBERON:0001625	94.87	gold quality
upper lobe of left lung	UBERON:0008952	94.87	gold quality
gall bladder	UBERON:0002110	94.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.84	gold quality
mucosa of stomach	UBERON:0001199	94.63	gold quality
endocervix	UBERON:0000458	94.56	gold quality
mucosa of transverse colon	UBERON:0004991	94.52	gold quality
right ovary	UBERON:0002118	94.45	gold quality
stomach	UBERON:0000945	94.43	gold quality
saliva-secreting gland	UBERON:0001044	94.35	gold quality
apex of heart	UBERON:0002098	94.35	gold quality
esophagus	UBERON:0001043	94.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

100 targeting GORASP1, 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-6740-5P	100.00	65.64	932
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-1197	99.70	67.75	1027

Literature-anchored findings (GeneRIF, showing 25)

• the GRASP domain alone of GRASP65 inhibits mitotic fragmentation of the Golgi apparatus (PMID:15576368)
• GRASP65 may function as a signal integrator controlling the cell growth (PMID:15834132)
• GRASP65 has a role in the regulation of spindle dynamics rather than a direct role in the stacking of Golgi cisternae (PMID:15888544)
• Ribbon formation requires the Golgi proteins GM130 and GRASP65. (PMID:16489344)
• Mitochondria bearing GRASP65 became tethered to one another, and this depended on a GRASP65 PDZ domain that was also required for GRASP65 self-interaction. (PMID:19581411)
• Data demonstrate that both GRASP55 and 65 are needed for the efficient transport to and through the Golgi complex, thus highlighting a novel role for the GRASPs in membrane trafficking. (PMID:19840934)
• These results demonstrate that GRASP55 and GRASP65 stack mammalian Golgi cisternae via a common mechanism. (PMID:20083603)
• GRASP65 has a role in Golgi cisternal stacking and cell cycle progression (PMID:20214750)
• the mechanism of phosphoinhibition as direct inhibition by PLK1 of the PDZ ligand underlying the GRASP65 self-interaction. (PMID:20937827)
• The C-terminal fragments of GRASP65 produced following caspase cleavage are targeted to mitochondria, and ectopic expression of these sensitises HeLa cells to Fas ligand. (PMID:21368855)
• propose that GRASP55/65 are negative regulators of exocytic transport and that this slowdown helps to ensure more complete protein glycosylation in the Golgi stack and proper sorting at the trans-Golgi network (PMID:23552074)
• Cisternal-specific functions of GRASP65 and GRASP55 in continuity, compartmentalization, and function of the Golgi ribbon. (PMID:24227884)
• Mutagenesis experiments support these structural observations and demonstrate that they are required for GRASP65-GM130 association. (PMID:26363069)
• In cells, Mena and actin were required for Golgi ribbon formation after nocodazole washout; in vitro, Mena and microfilaments enhanced GRASP65 oligomerization and Golgi membrane fusion. Thus Mena interacts with GRASP65 to promote local actin polymerization, which facilitates Golgi ribbon linking. (PMID:26538023)
• The authors determined that Golgi membrane ribbon fragmentation increased during the early cytoplasmic phase of cytomegalovirus virion assembly and that Golgi membrane fragmentation in infected cells was dependent on the phosphorylation of an integral cis-Golgi protein, Grasp65. (PMID:27703074)
• In situ proximity ligation assays of Golgi localization of alpha-mannosidase IA at giantin versus GM130-GRASP65 site, and absence or presence of N-glycans terminated with alpha3-mannose on trans-Golgi glycosyltransferases may be useful for distinguishing indolent from aggressive prostate cancer cells. (PMID:28782625)
• Results demonstrate a critical role for GRASP55 and GRASP65 in maintaining the stacked structure of the Golgi, which is required for accurate posttranslational modifications in the Golgi. Additionally, the GRASP knockout cell lines developed in this study will be useful tools for studying the role of GRASP proteins in other important cellular processes. (PMID:28814501)
• DjA1 interacts with GRASP65 to enhance Golgi structure formation through the promotion of GRASP65 trans-oligomerization. (PMID:30566031)
• GRASP65 modulates Golgi structure and microtubule organization during cell division. (PMID:31336000)
• Markers of malignant prostate cancer cells: Golgi localization of alpha-mannosidase 1A at GM130-GRASP65 site and appearance of high mannose N-glycans on cell surface. (PMID:32331836)
• Biophysical characterization of intrinsically disordered human Golgi matrix protein GRASP65. (PMID:32822731)
• Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure. (PMID:33301566)
• GRASP depletion-mediated Golgi fragmentation impairs glycosaminoglycan synthesis, sulfation, and secretion. (PMID:35312866)
• Identification of GRASP65, and demonstration that it functions in the formation of stacked Golgi cisternae. (PMID:9346242)
• A study showing that GRASP65 binds directly to the coiled-coil vesicle tethering factor GM130, and targets it to Golgi membranes. (PMID:9628863)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gorasp1a	ENSDARG00000003068
danio_rerio	gorasp1b	ENSDARG00000101928
mus_musculus	Gorasp1	ENSMUSG00000032513
rattus_norvegicus	Gorasp1	ENSRNOG00000018047
drosophila_melanogaster	Grasp65	FBGN0036919
caenorhabditis_elegans		WBGENE00021536

Paralogs (1): GORASP2 (ENSG00000115806)

Protein

Protein identifiers

Golgi reassembly-stacking protein 1 — Q9BQQ3 (reviewed: Q9BQQ3)

Alternative names: Golgi peripheral membrane protein p65, Golgi phosphoprotein 5, Golgi reassembly-stacking protein of 65 kDa

All UniProt accessions (26): Q9BQQ3, A0A8Q3SHP4, A0A8Q3SHQ3, A0A8Q3SHQ7, A0A8Q3SHR6, A0A8Q3SHU6, A0A8Q3SHU9, A0A8Q3SHV7, A0A8Q3SHW7, A0A8Q3SI07, A0A8Q3SI18, A0A8Q3SIN9, A0A8Q3WKF7, A0A8Q3WKF9, A0A8Q3WKH3, A0A8Q3WKI0, A0A8Q3WKM5, A0A8Q3WL08, A0A8Q3WLK9, B3KPY8, B4E1H8, C9J0V5, C9J5S6, C9J9V9, G3V0G1, H7C0J2

UniProt curated annotations — full annotation on UniProt →

Function. Key structural protein of the Golgi apparatus. The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon. Acting in concert with GORASP2/GRASP55, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks. However, other studies suggest that GORASP1 plays an important role in assembly and membrane stacking of the cisternae, and in the reassembly of Golgi stacks after breakdown during mitosis. Caspase-mediated cleavage of GORASP1 is required for fragmentation of the Golgi during apoptosis. Also mediates, via its interaction with GOLGA2/GM130, the docking of transport vesicles with the Golgi membranes. Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane.

Subunit / interactions. Homodimer. Forms higher-order oligomers under interphase but not mitotic conditions. Dimers of the protein on one membrane might be able to interact with dimers on another and so stack cisternae. Interacts with the C-terminus of GOLGA2/GM130 under both mitotic and non-mitotic conditions. The interaction is critical for the correct targeting of both proteins to the cis-Golgi. Interacts with TMED2 and TMED3.

Subcellular location. Golgi apparatus. cis-Golgi network membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane.

Post-translational modifications. Phosphorylated by CDC2/B1 and PLK kinases during mitosis. Phosphorylation cycle correlates with the cisternal stacking cycle. Phosphorylation of the homodimer prevents the association of dimers into higher-order oligomers, leading to cisternal unstacking. Target for caspase-3 cleavage during apoptosis. The cleavage contributes to Golgi fragmentation and occurs very early in the execution phase of apoptosis. Myristoylated.

Similarity. Belongs to the GORASP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BQQ3-1	1	yes
Q9BQQ3-2	2
Q9BQQ3-3	3

RefSeq proteins (5): NP_001265718, NP_001265719, NP_001397655, NP_001397660, NP_114105* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007583	GRASP55_65	Family
IPR024958	GRASP_PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily

Pfam: PF04495

UniProt features (50 total): strand 13, turn 6, helix 5, region of interest 5, modified residue 4, splice variant 4, compositionally biased region 3, binding site 3, domain 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4REY	X-RAY DIFFRACTION	1.96
6G8W	X-RAY DIFFRACTION	2.12
6G8T	X-RAY DIFFRACTION	2.67

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQQ3-F1	64.10	0.34

Functional residue map

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

Ligand- & substrate-binding residues (3): 18; 20; 103

Post-translational modifications (5): 216, 362, 364, 373, 2

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-162658	Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-6807878	COPI-mediated anterograde transport

MSigDB gene sets: 167 (showing top): GOBP_DENDRITE_DEVELOPMENT, GCM_MAP4K4, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GCM_GSPT1, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, BROWNE_HCMV_INFECTION_24HR_UP

GO Biological Process (6): protein N-linked glycosylation (GO:0006487), Golgi organization (GO:0007030), protein transport (GO:0015031), negative regulation of dendrite morphogenesis (GO:0050774), establishment of protein localization to plasma membrane (GO:0061951), Golgi ribbon formation (GO:0090161)

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Mitotic Prophase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Golgi apparatus	2
bounding membrane of organelle	2
intracellular membrane-bounded organelle	2
glycoprotein biosynthetic process	1
organelle organization	1
endomembrane system organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
negative regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
negative regulation of neurogenesis	1
establishment of protein localization to membrane	1
Golgi organization	1
cation binding	1
binding	1
cytoplasm	1
endomembrane system	1
endoplasmic reticulum-Golgi intermediate compartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GORASP1	GOLGA2	Q08379	996
GORASP1	USO1	O60763	968
GORASP1	GOLGB1	Q14789	920
GORASP1	BLZF1	Q9H2G9	919
GORASP1	GOLGA3	Q08378	841
GORASP1	GOLPH3	Q9H4A6	817
GORASP1	GOLGA5	Q8TBA6	773
GORASP1	STK25	O00506	734
GORASP1	STX5	Q13190	713
GORASP1	TRIP11	Q15643	674
GORASP1	GCC2	Q8IWJ2	667
GORASP1	GOSR1	O95249	642
GORASP1	PLK1	P53350	611
GORASP1	SEC24B	O95487	599
GORASP1	GOLGA1	Q92805	599

IntAct

418 interactions, top by confidence:

A	B	Type	Score
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
GORASP1	AGPS	psi-mi:“MI:0915”(physical association)	0.780
AGPS	GORASP1	psi-mi:“MI:0915”(physical association)	0.780
SEC31A	SEC13	psi-mi:“MI:0914”(association)	0.730
LONRF1	GORASP1	psi-mi:“MI:0915”(physical association)	0.720
GORASP1	LONRF1	psi-mi:“MI:0915”(physical association)	0.720
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
GORASP1	rep	psi-mi:“MI:0915”(physical association)	0.660
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
E	GORASP1	psi-mi:“MI:0915”(physical association)	0.610
E	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.610
PRKD2	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.590
SCRN1	GORASP1	psi-mi:“MI:0915”(physical association)	0.560
GORASP1	SCRN1	psi-mi:“MI:0915”(physical association)	0.560
NEFL	GORASP1	psi-mi:“MI:0915”(physical association)	0.560
GORASP1	TRAF4	psi-mi:“MI:0915”(physical association)	0.560
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
GORASP1	PPP6R2	psi-mi:“MI:0914”(association)	0.530
E6	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (173): GORASP1 (Two-hybrid), GORASP1 (Two-hybrid), LONRF1 (Two-hybrid), GORASP1 (Affinity Capture-MS), GORASP1 (Affinity Capture-MS), GORASP1 (Affinity Capture-MS), GORASP1 (Affinity Capture-MS), GORASP1 (Affinity Capture-MS), GORASP1 (Affinity Capture-MS), GORASP1 (Affinity Capture-MS), GOLGA2 (Affinity Capture-MS), CLIP1 (Affinity Capture-MS), BLZF1 (Affinity Capture-MS), TES (Affinity Capture-MS), USP46 (Affinity Capture-MS)

ESM2 similar proteins: B5DEH0, G5E5X0, O09139, O35254, O70405, O75385, O94966, P42335, P59729, Q01094, Q14209, Q16254, Q3UH66, Q3UIZ8, Q4JF29, Q5DTT2, Q5SSZ5, Q5XIS1, Q60700, Q61501, Q63796, Q68CZ2, Q6AW68, Q6BCB4, Q6P0Q8, Q75NY9, Q76I76, Q76I79, Q76N89, Q7TNN8, Q7TPK6, Q7TSI1, Q80U38, Q80UE6, Q80UF7, Q8BLR5, Q8IUC6, Q8TB24, Q8TE77, Q8WYL5

Diamond homologs: O35254, Q04410, Q10149, Q91X51, Q99JX3, Q9BQQ3, Q9H8Y8, Q9R064, O00233, O94393, P40555, Q10920, Q3SZ19, Q9CR00, Q9VFS8, Q9WTV5

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
GOLGA2	“up-regulates quantity by stabilization”	GORASP1	binding
CASP3	“down-regulates quantity by destabilization”	GORASP1	cleavage
GOLGA2	“up-regulates activity”	GORASP1	binding
PLK1	“down-regulates quantity”	GORASP1	phosphorylation
ERK1/2	“down-regulates activity”	GORASP1	phosphorylation
CyclinB/CDK1	“down-regulates activity”	GORASP1	phosphorylation
CDK1	“down-regulates activity”	GORASP1	phosphorylation
MAPK1	“down-regulates activity”	GORASP1	phosphorylation
CASP3	“up-regulates activity”	GORASP1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 182 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
EPHB-mediated forward signaling	5	11.3×	4e-03
RHOF GTPase cycle	5	11.1×	4e-03
RHOQ GTPase cycle	7	10.8×	4e-04
RHOJ GTPase cycle	6	10.3×	1e-03
NRAGE signals death through JNK	6	9.4×	2e-03
Cell death signalling via NRAGE, NRIF and NADE	5	9.4×	7e-03
RHOB GTPase cycle	7	9.2×	9e-04
G alpha (12/13) signalling events	7	8.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	12.4×	6e-03
cell-cell adhesion	11	6.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2305 predictions. Top by Δscore:

Variant	Effect	Δscore
3:39099347:CAGTA:C	donor_loss	1.0000
3:39099348:AGTAC:A	donor_loss	1.0000
3:39099349:GTACC:G	donor_loss	1.0000
3:39099350:TAC:T	donor_loss	1.0000
3:39099351:A:C	donor_loss	1.0000
3:39099352:C:G	donor_loss	1.0000
3:39099364:A:C	donor_gain	1.0000
3:39099499:AGGGC:A	acceptor_gain	1.0000
3:39099500:GGGC:G	acceptor_gain	1.0000
3:39099501:GGC:G	acceptor_gain	1.0000
3:39099502:GC:G	acceptor_gain	1.0000
3:39099503:CC:C	acceptor_gain	1.0000
3:39099504:C:CC	acceptor_gain	1.0000
3:39100789:T:TA	donor_gain	1.0000
3:39100790:C:A	donor_gain	1.0000
3:39100878:C:CC	acceptor_gain	1.0000
3:39101014:ACCT:A	donor_gain	1.0000
3:39101015:CCTC:C	donor_gain	1.0000
3:39101017:T:TA	donor_gain	1.0000
3:39101099:CATC:C	acceptor_gain	1.0000
3:39101103:C:CA	acceptor_loss	1.0000
3:39101104:T:A	acceptor_loss	1.0000
3:39102882:C:CC	acceptor_gain	1.0000
3:39103471:ACCAG:A	donor_gain	1.0000
3:39103472:CCAGC:C	donor_gain	1.0000
3:39098487:CAC:C	acceptor_gain	0.9900
3:39098488:ACCT:A	acceptor_loss	0.9900
3:39098490:C:CA	acceptor_loss	0.9900
3:39098491:T:A	acceptor_loss	0.9900
3:39098739:ACCAC:A	donor_gain	0.9900

AlphaMissense

2849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:39101080:G:T	A124D	0.999
3:39102686:G:C	H114D	0.999
3:39102756:C:A	W90C	0.999
3:39102756:C:G	W90C	0.999
3:39102758:A:G	W90R	0.999
3:39102758:A:T	W90R	0.999
3:39102769:G:T	P86H	0.999
3:39100480:C:T	G197E	0.998
3:39100498:C:T	G191E	0.998
3:39100761:C:A	W184C	0.998
3:39100761:C:G	W184C	0.998
3:39100774:G:T	P180H	0.998
3:39100817:A:C	Y166D	0.998
3:39100825:A:G	L163P	0.998
3:39102689:A:G	W113R	0.998
3:39102689:A:T	W113R	0.998
3:39102733:G:T	A98D	0.998
3:39102820:A:G	L69P	0.998
3:39102850:A:G	L59P	0.998
3:39103534:G:T	A28D	0.998
3:39100763:A:G	W184R	0.997
3:39100763:A:T	W184R	0.997
3:39100792:C:G	R174P	0.997
3:39101051:C:G	D134H	0.997
3:39101065:A:G	L129P	0.997
3:39102736:C:A	G97V	0.997
3:39102736:C:T	G97D	0.997
3:39102737:C:G	G97R	0.997
3:39102787:C:G	R80P	0.997
3:39103498:A:T	I40N	0.997

dbSNP variants (sampled 300 via entrez): RS1000439869 (3:39102503 G>A), RS1000691482 (3:39105655 A>G), RS1001036851 (3:39103993 C>T), RS1001148205 (3:39096525 C>T), RS1001708525 (3:39099709 G>A,C,T), RS1002365981 (3:39107119 A>G), RS1002553802 (3:39097205 C>G,T), RS1002696061 (3:39108139 A>C,G), RS1002725805 (3:39107921 G>A,C), RS1002972804 (3:39101509 C>G,T), RS1003172573 (3:39104140 A>C), RS1003311313 (3:39101986 GA>G,GAA), RS1003432042 (3:39096442 T>C), RS1003555923 (3:39098807 T>C), RS1003758441 (3:39105401 C>A)

Disease associations

OMIM: gene MIM:606867 | 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
GCST002367_11	Social communication problems	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005427	social communication impairment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	decreases expression, affects cotreatment	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Oxygen	decreases expression	1
Phthalic Acids	decreases methylation	1
Selenium	increases expression	1
Smoke	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

4 cell lines: 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E3WM	HEK293 GRASP55/GRASP65 DKO	Transformed cell line	Female
CVCL_E3WN	HEK293 GRASP65 KO	Transformed cell line	Female
CVCL_E3WQ	HeLa GRASP55/GRASP65 DKO	Cancer cell line	Female
CVCL_E3WR	HeLa GRASP65 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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