GORASP2

Summary

GORASP2 (golgi reassembly stacking protein 2, HGNC:17500) is a protein-coding gene on chromosome 2q31.1, encoding Golgi reassembly-stacking protein 2 (Q9H8Y8). Key structural protein of the Golgi apparatus.

This gene encodes a member of the Golgi reassembly stacking protein family. These proteins may play a role in the stacking of Golgi cisternae and Golgi ribbon formation, as well as Golgi fragmentation during apoptosis or mitosis. The encoded protein also plays a role in the intracellular transport of transforming growth factor alpha and may function as a molecular chaperone. A pseudogene of this gene is located on the short arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 26003 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 82 total
• GTEx eGene: eQTL in 15 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.52 (intermediate), LOEUF 0.72 (unconstrained)
• MANE Select transcript: NM_015530
• Notable: 82 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17500
Approved symbol	GORASP2
Name	golgi reassembly stacking protein 2
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	GRASP55, GRS2, GOLPH6
Ensembl gene	ENSG00000115806
Ensembl biotype	protein_coding
OMIM	608693
Entrez	26003

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 16 nonsense_mediated_decay, 14 protein_coding, 3 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000234160

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 2, TSL 4: 2, TSL 5: 3

ENST00000234160, ENST00000442798, ENST00000444801, ENST00000454751, ENST00000455067, ENST00000471559, ENST00000486498, ENST00000488928, ENST00000493692, ENST00000497674, ENST00000497928, ENST00000871663, ENST00000871664, ENST00000871665, ENST00000871666, ENST00000871667, ENST00000871668, ENST00000871669, ENST00000917130, ENST00000972174, ENST00000972175, ENST00000972176, ENST00000993339, ENST00000993340, ENST00000993341, ENST00000993342, ENST00000993343, ENST00000993344, ENST00001027100, ENST00001027104, ENST00001082684, ENST00001082686, ENST00001082687, ENST00001082688, ENST00001112279, ENST00001142836

RefSeq mRNA: 2 — MANE Select: NM_015530 NM_001201428, NM_015530

CCDS: CCDS33325

Canonical transcript exons

ENST00000234160 — 10 exons

Exon	Start	End
ENSE00000882723	170965790	170967130
ENSE00001947947	170929253	170929403
ENSE00003474112	170950204	170950290
ENSE00003487200	170949539	170949742
ENSE00003491939	170948350	170948430
ENSE00003499588	170954650	170954782
ENSE00003575527	170956436	170956559
ENSE00003581581	170951328	170951458
ENSE00003585070	170961663	170961749
ENSE00003621429	170962839	170962946

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.6495 / max 1527.3907, expressed in 1827 samples.

Highest expression (Bgee): sperm, secondary oocyte, male germ cell, oocyte, endothelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GORASP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	4.4e-24	+0.73	2:170935919:C:T
Testis	eqtl	2.1e-15	+0.35	2:170906372:A:G
Muscle Skeletal	eqtl	2.4e-08	-0.35	2:170929058:G:C
Nerve Tibial	eqtl	2.0e-05	-0.21	2:170929058:G:C
Esophagus Mucosa	eqtl	1.6e-03	-0.14	2:171631067:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.0e-03	-0.17	2:170929058:G:C
Small Intestine Terminal Ileum	eqtl	3.9e-03	-1.73	2:170564673:A:C
Artery Aorta	eqtl	8.3e-03	+0.35	2:170511873:A:G
Brain Substantia nigra	eqtl	9.8e-03	-0.51	2:170929058:G:C
Muscle Skeletal	sqtl	1.7e-02	+0.28	2:170969163:T:C
Artery Tibial	eqtl	1.8e-02	-0.16	2:170929058:G:C
Whole Blood	eqtl	2.0e-02	+0.08	2:171179964:A:G
Heart Atrial Appendage	eqtl	2.4e-02	-0.11	2:171269141:C:G
Skin Sun Exposed Lower leg	eqtl	3.3e-02	-0.11	2:171227837:A:G
Adipose Visceral Omentum	eqtl	4.2e-02	-0.08	2:170579300:C:T
Brain Cerebellum	eqtl	4.5e-02	-0.37	2:170901549:G:C
Cells Cultured fibroblasts	eqtl	4.5e-02	-0.14	2:170901549:G:C

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
23644	68.9743	1827
23645	5.6881	1757
23646	4.3353	1714
23647	1.2739	753
23643	1.1563	838
23641	0.5906	299
23642	0.5058	274
23640	0.0540	17
23638	0.0411	15
23639	0.0301	5

Top tissues by expression

showing 100 of 303 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.08	gold quality
secondary oocyte	CL:0000655	98.84	gold quality
male germ cell	CL:0000015	98.31	gold quality
oocyte	CL:0000023	98.29	gold quality
endothelial cell	CL:0000115	98.11	gold quality
tibia	UBERON:0000979	98.05	gold quality
parotid gland	UBERON:0001831	97.66	gold quality
islet of Langerhans	UBERON:0000006	97.51	gold quality
esophagus squamous epithelium	UBERON:0006920	97.01	gold quality
stromal cell of endometrium	CL:0002255	97.00	gold quality
cartilage tissue	UBERON:0002418	96.57	gold quality
pancreas	UBERON:0001264	96.56	gold quality
epithelium of esophagus	UBERON:0001976	96.53	gold quality
corpus epididymis	UBERON:0004359	96.48	gold quality
palpebral conjunctiva	UBERON:0001812	96.43	gold quality
squamous epithelium	UBERON:0006914	96.43	gold quality
body of pancreas	UBERON:0001150	96.39	gold quality
placenta	UBERON:0001987	96.20	gold quality
caput epididymis	UBERON:0004358	96.14	gold quality
smooth muscle tissue	UBERON:0001135	96.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.12	gold quality
rectum	UBERON:0001052	95.92	gold quality
pancreatic ductal cell	CL:0002079	95.90	gold quality
colonic mucosa	UBERON:0000317	95.88	gold quality
gingival epithelium	UBERON:0001949	95.88	gold quality
eye	UBERON:0000970	95.86	gold quality
pituitary gland	UBERON:0000007	95.82	gold quality
ileal mucosa	UBERON:0000331	95.82	gold quality
type B pancreatic cell	CL:0000169	95.67	gold quality
gingiva	UBERON:0001828	95.67	gold quality
adenohypophysis	UBERON:0002196	95.60	gold quality
cervix squamous epithelium	UBERON:0006922	95.59	gold quality
saliva-secreting gland	UBERON:0001044	95.55	gold quality
seminal vesicle	UBERON:0000998	95.35	gold quality
thoracic aorta	UBERON:0001515	95.35	gold quality
ascending aorta	UBERON:0001496	95.33	gold quality
periodontal ligament	UBERON:0008266	95.32	gold quality
right coronary artery	UBERON:0001625	95.25	gold quality
left adrenal gland	UBERON:0001234	95.21	gold quality
minor salivary gland	UBERON:0001830	95.20	gold quality
heart right ventricle	UBERON:0002080	95.20	gold quality
parietal pleura	UBERON:0002400	95.16	gold quality
visceral pleura	UBERON:0002401	95.15	gold quality
decidua	UBERON:0002450	95.15	gold quality
right adrenal gland	UBERON:0001233	95.14	gold quality
mouth mucosa	UBERON:0003729	95.14	gold quality
aorta	UBERON:0000947	95.08	gold quality
choroid plexus epithelium	UBERON:0003911	95.06	gold quality
pleura	UBERON:0000977	95.05	gold quality
endometrium	UBERON:0001295	95.00	gold quality
nasal cavity mucosa	UBERON:0001826	94.97	gold quality
right adrenal gland cortex	UBERON:0035827	94.93	gold quality
descending thoracic aorta	UBERON:0002345	94.91	gold quality
popliteal artery	UBERON:0002250	94.90	gold quality
left adrenal gland cortex	UBERON:0035825	94.90	gold quality
tibial artery	UBERON:0007610	94.89	gold quality
adrenal gland	UBERON:0002369	94.88	gold quality
tonsil	UBERON:0002372	94.87	gold quality
skin of hip	UBERON:0001554	94.83	gold quality
artery	UBERON:0001637	94.82	gold quality
esophagus mucosa	UBERON:0002469	94.82	gold quality
adrenal cortex	UBERON:0001235	94.78	gold quality
oviduct epithelium	UBERON:0004804	94.75	gold quality
endocervix	UBERON:0000458	94.73	gold quality
ectocervix	UBERON:0012249	94.73	gold quality
left coronary artery	UBERON:0001626	94.72	gold quality
epithelial cell of pancreas	CL:0000083	94.71	gold quality
left uterine tube	UBERON:0001303	94.62	gold quality
uterine cervix	UBERON:0000002	94.55	gold quality
uterus	UBERON:0000995	94.52	gold quality
gall bladder	UBERON:0002110	94.51	gold quality
right atrium auricular region	UBERON:0006631	94.50	gold quality
coronary artery	UBERON:0001621	94.46	gold quality
fallopian tube	UBERON:0003889	94.44	gold quality
cardiac atrium	UBERON:0002081	94.40	gold quality
synovial joint	UBERON:0002217	94.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.32	gold quality
mammary gland	UBERON:0001911	94.25	gold quality
thoracic mammary gland	UBERON:0005200	94.23	gold quality
skin of leg	UBERON:0001511	94.21	gold quality
cauda epididymis	UBERON:0004360	94.21	gold quality
body of uterus	UBERON:0009853	94.20	gold quality
pigmented layer of retina	UBERON:0001782	94.18	gold quality
body of stomach	UBERON:0001161	94.16	gold quality
retina	UBERON:0000966	94.15	gold quality
colonic epithelium	UBERON:0000397	94.14	gold quality
mammalian vulva	UBERON:0000997	94.14	gold quality
bone marrow cell	CL:0002092	94.13	gold quality
female reproductive system	UBERON:0000474	94.13	gold quality
esophagus	UBERON:0001043	94.10	gold quality
epithelium of mammary gland	UBERON:0003244	94.09	gold quality
right testis	UBERON:0004534	94.06	gold quality
left testis	UBERON:0004533	94.04	gold quality
germinal epithelium of ovary	UBERON:0001304	94.03	gold quality
zone of skin	UBERON:0000014	93.98	gold quality
adult organism	UBERON:0007023	93.96	gold quality
myometrium	UBERON:0001296	93.94	gold quality
mammary duct	UBERON:0001765	93.90	gold quality
sigmoid colon	UBERON:0001159	93.85	gold quality
penis	UBERON:0000989	93.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.46

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	85.5
Frontal cortex	tissue	84.2
Spinal cord	tissue	68.7
Corpus callosum	tissue	67.2
Thalamus	tissue	66.4
Midbrain	tissue	66.1
Salivary gland	tissue	64.4	high
Superior colliculi	tissue	63.5
Pancreas	tissue	63.3	medium
Hippocampal formation	tissue	63.3
Medulla oblongata	tissue	61.6
Pons	tissue	61.0
Putamen	tissue	61.0
Substantia nigra	tissue	59.2
Cervix	tissue	58.9	medium
Prefrontal cortex	tissue	58.5
Cerebral cortex	tissue	58.5	low
Somatosensory cortex	tissue	58.1
Epididymis	tissue	57.0	high
Basal ganglia	tissue	56.5	not detected
Pituitary gland	tissue	56.2
Septum	tissue	55.9
Hypothalamus	tissue	55.6
Occipital cortex	tissue	55.6
Ventral forebrain	tissue	54.4
Heart muscle	tissue	54.0	low
Motor cortex	tissue	52.7
Placenta	tissue	52.1	medium
Urinary bladder	tissue	49.8	medium
Seminal vesicle	tissue	49.6	high
Olfactory bulb	tissue	49.1
Periaqueductal gray	tissue	49.0
Temporal cortex	tissue	48.9
Retrosplenial and cingulate cortex	tissue	48.7
Cerebellum	tissue	48.5	low
Retrosplenial cortex	tissue	48.1
Thyroid gland	tissue	47.6	medium
Entorhinal cortex	tissue	47.5
Parathyroid gland	tissue	44.5	low
Esophagus	tissue	44.0	medium
Smooth muscle	tissue	43.0	not detected
Liver	tissue	42.6	not detected
Amygdala	tissue	41.6
Insular cortex	tissue	41.5
Tonsil	tissue	41.4	medium
Rectum	tissue	41.0	high
Colon	tissue	40.8	high
Adrenal gland	tissue	40.8	medium
Endometrium 1	tissue	40.4	high
Stomach 1	tissue	39.7	low
Vagina	tissue	39.4	medium
Thymus	tissue	39.0
Ovary	tissue	38.9	medium
Prostate	tissue	38.2	high
Breast	tissue	37.9	medium
Lymph node	tissue	37.3	medium
Skeletal muscle	tissue	37.2	not detected
Skin 1	tissue	36.5	medium
Duodenum	tissue	36.1	high
Tongue	tissue	35.5

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (68.7), White matter (67.2), Dorsal spinal cord (65.2), Dorsal hippocampus (63.3), Ventral hippocampus (55.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GORASP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 75 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-7844-5P	99.55	68.56	1428

Functional genomics

gnomAD constraint: pLI 0.522, LOEUF 0.724, missense Z 0.919 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000234160 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:170,929,341–170,954,739	194 / 270.4	0.72	no
2:170,954,740–170,966,127	297 / 292.3	1.02	no

Literature-anchored findings (GeneRIF, showing 22)

• GRASP55 forms an effector complex for the small GTPase rab2, together with a conserved coiled-coil protein golgin-45 (JEM-1). (PMID:11739401)
• GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity (PMID:11815631)
• MEK1/ERK regulation of GRASP55-mediated Golgi linking is a control point in cell cycle progression (PMID:18434598)
• 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)
• GRASP55 may function as an adaptor protein coupling MT1-MMP with furin, thus leading to the activation of the zymogen. (PMID:20608975)
• 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)
• GRASP55 interacts with CD83 shortly after induction of dendritic cells maturation. (PMID:25701785)
• binding site at the cleft between the PDZ1 and PDZ2 domains of GRASP65 is dominated by hydrophobic interactions with GM130 that are not observed in the GRASP55-Golgin45 complex (PMID:28049725)
• 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)
• here we identified a novel GORASP2-ALK rearrangement in a patient with ALK + LBCL with a unique ALK immunohistochemical staining pattern. (PMID:30187817)
• GORASP2/GRASP55 collaborates with the PtdIns3K UVRAG complex to facilitate autophagosome-lysosome fusion. (PMID:30894053)
• structural aspects of the human Golgi matrix protein GRASP55 in solution (PMID:31102680)
• that SIRT2 regulates Golgi structure by modulating GRASP55 acetylation levels (PMID:31604796)
• Nucleation-dependent amyloid fibrillation of human GRASP55 in aqueous solution. (PMID:31915857)
• GRASP55: A Multifunctional Protein. (PMID:32067616)
• Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure. (PMID:33301566)
• An mTORC1-GRASP55 signaling axis controls unconventional secretion to reshape the extracellular proteome upon stress. (PMID:34245671)
• GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis. (PMID:34516001)
• GRASP depletion-mediated Golgi fragmentation impairs glycosaminoglycan synthesis, sulfation, and secretion. (PMID:35312866)
• Golgi Reassembly Stacking Protein 2 Modulates Myometrial Contractility during Labor by Affecting ATP Production. (PMID:37373263)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gorasp2	ENSDARG00000015126
mus_musculus	Gorasp2	ENSMUSG00000014959
rattus_norvegicus	Gorasp2	ENSRNOG00000023386
drosophila_melanogaster	Grasp65	FBGN0036919
caenorhabditis_elegans		WBGENE00021536

Paralogs (1): GORASP1 (ENSG00000114745)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2135962) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
postnatal growth retardation	1
male infertility	1
abnormal spermiogenesis	1
asthenozoospermia	1
oligozoospermia	1
abnormal spermatocyte morphology	1
abnormal acrosome morphology	1
abnormal sperm head morphology	1
abnormal sperm midpiece morphology	1
abnormal Golgi apparatus morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharomyces cerevisiae S288C	Q04410	42.6%	Diamond
Schizosaccharomyces pombe 972h-	Q10149	38.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MYO3B-AS1	ncRNA	101929753
GAD1-AS1	ncRNA	137805480
MYO3B	protein-coding	140469
GAD1	protein-coding	2571
ERICH2	protein-coding	285141
SP5	protein-coding	389058
LINC01124	ncRNA	440925
ERICH2-DT	ncRNA	101926913
TLK1	protein-coding	9874

Protein

Protein identifiers

Golgi reassembly-stacking protein 2 — Q9H8Y8 (reviewed: Q9H8Y8)

Alternative names: Golgi phosphoprotein 6, Golgi reassembly-stacking protein of 55 kDa, p59

All UniProt accessions (5): Q9H8Y8, F8WBR9, F8WEG2, F8WEH9, F8WF79

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 GORASP1/GRASP65, 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 GORASP2 plays a role in the assembly and membrane stacking of the Golgi cisternae, and in the process by which Golgi stacks reform after breakdown during mitosis and meiosis. May regulate the intracellular transport and presentation of a defined set of transmembrane proteins, such as transmembrane TGFA. Required for normal acrosome formation during spermiogenesis and normal male fertility, probably by promoting colocalization of JAM2 and JAM3 at contact sites between germ cells and Sertoli cells. Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane.

Subunit / interactions. Homodimer. Homooligomer. ER stress induces phosphorylation-dependent monomerization. Interacts with BLZF1/Golgin 45. Identified in a complex with RAB2 and GORASP2. Interacts with JAM2 and JAM3. Interacts with members of the p24 cargo receptors. Interacts with CNIH1 and the cytoplasmic domain of transmembrane TGFA, prior its transit in the trans-Golgi. Interacts with KCTD5. Interacts with TMED2 and TMED3. Interacts with SEC16A in response to ER stress. Interacts (via PDZ GRASP-type 1 domain) with core-glycosylated CFTR in response to ER stress.

Subcellular location. Golgi apparatus membrane. Endoplasmic reticulum membrane. Golgi apparatus.

Post-translational modifications. Myristoylated. Myristoylation is essential for the Golgi targeting. Palmitoylated. Phosphorylated in mitotic cells. ER stress-induced phosphorylation at Ser-441 induces monomerization and subsequent relocalization from Golgi to ER which is essential for mediating unconventional (ER/Golgi-independent) trafficking of CFTR to the cell membrane.

Similarity. Belongs to the GORASP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H8Y8-1	1	yes
Q9H8Y8-2	2
Q9H8Y8-3	3

RefSeq proteins (2): NP_001188357, NP_056345* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF04495

UniProt features (69 total): strand 14, mutagenesis site 13, modified residue 12, helix 8, turn 6, sequence conflict 4, region of interest 3, domain 2, splice variant 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
3RLE	Crystal Structure of GRASP55 GRASP domain (residues 7-208)	X-RAY DIFFRACTION	1.65
4EDJ	Crystal structure of the GRASP55 GRASP Domain with a phosphomimetic mutation (S189D)	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H8Y8-F1	65.69	0.34

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IH enhanced · IF enhanced

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 (13)

Type	Positions
Phosphoserine	214, 409, 436, 441, 449, 451
Phosphothreonine	222, 225, 415, 433
N-myristoyl glycine	2
Dimethylated arginine	30, 47

Mutagenesis-validated functional residues (13)

Position	Phenotype
2	abolishes myristoylation. loss of its ability to mediate unconventional (er/golgi-independent) trafficking of cftr to the cell membrane. no …
59	abolishes organelle clustering; when associated with s-100.
100	abolishes organelle clustering; when associated with a-59.
148	enhances homodimerization. loss of er stress-induced relocalization from golgi to er.
189	phosphomimetic mutation that decreases the ability to promote organelle clustering.
222	abolishes mitotic phosphorylation; when associated with a-225.
225	abolishes mitotic phosphorylation; when associated with a-222.
441	loss of phosphorylation and its ability to mediate unconventional (er/golgi-independent) trafficking of cftr to the cell membrane. inhibits …
441	phosphomimetic mutant. no loss of its ability to mediate unconventional (er/golgi-independent) trafficking of cftr to the cell membrane …
449	loss of phosphorylation. does not inhibit er stress-mediated disruption of homodimerization.
449	phosphomimetic mutant. no disruption of homodimerization.
451	loss of phosphorylation. does not inhibit er stress-mediated disruption of homodimerization.
451	phosphomimetic mutant. partial disruption of homodimerization.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-162658	Golgi Cisternae Pericentriolar Stack Reorganization	curated
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-68886	M Phase	—
R-HSA-68875	Mitotic Prophase	—

MSigDB gene sets: 176 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, AP2_Q3, GOBP_MALE_GAMETE_GENERATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_ORGANELLE_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, BYSTROEM_CORRELATED_WITH_IL5_UP, CAIRO_HEPATOBLASTOMA_UP, RYTTCCTG_ETS2_B, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, BOYAULT_LIVER_CANCER_SUBCLASS_G12_UP

GO Biological Process (7): organelle organization (GO:0006996), Golgi organization (GO:0007030), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), response to endoplasmic reticulum stress (GO:0034976), establishment of protein localization to plasma membrane (GO:0061951), organelle assembly (GO:0070925)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Mitotic Prophase	1
M Phase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

19 GO namespaces:

Category	Terms
organelle organization	2
Golgi apparatus	2
intracellular membrane-bounded organelle	2
cellular component organization	1
endomembrane system organization	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
cellular response to stress	1
establishment of protein localization to membrane	1
cellular component assembly	1
binding	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
establishment of protein localization to plasma membrane	BP	direct assay
organelle assembly	BP	mutant phenotype
organelle organization	BP	mutant phenotype
response to endoplasmic reticulum stress	BP	direct assay
Golgi apparatus	CC	direct assay
Golgi membrane	CC	direct assay
endoplasmic reticulum membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,394 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GORASP2	BLZF1	Q9H2G9	987
GORASP2	RAB2A	P08886	888
GORASP2	TAMALIN	Q7Z6J2	749
GORASP2	GOLGA2	Q08379	654
GORASP2	GOLGA5	Q8TBA6	635
GORASP2	STX5	Q13190	620
GORASP2	GOLGB1	Q14789	593
GORASP2	GCC2	Q8IWJ2	593
GORASP2	GOLPH3	Q9H4A6	591
GORASP2	GOLGA3	Q08378	578
GORASP2	GOLGA1	Q92805	548
GORASP2	ARF1	P10947	515
GORASP2	TRIP11	Q15643	514
GORASP2	GOSR1	O95249	512
GORASP2	USO1	O60763	506

IntAct

Human interaction partners of GORASP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 503 partners by confidence:

Partner	Interaction type	MIscore	Records
GOLGA2	physical association	0.880	6
ACY3	physical association	0.870	15
TRAF2	physical association	0.870	9
CRYAA	physical association	0.840	12
DPYSL2	physical association	0.830	16
CBLB	physical association	0.830	8
EIF2B1	physical association	0.830	8
RPIA	physical association	0.830	8
PRPS1	physical association	0.800	7
PCBD1	physical association	0.800	6
ODC1	physical association	0.780	11
LONRF1	physical association	0.780	10
DMC1	physical association	0.780	8
C1orf94	physical association	0.780	7
DCTD	physical association	0.780	7
DUSP21	physical association	0.780	7
KCTD9	physical association	0.780	7
PNMA5	physical association	0.780	7
TRAF1	physical association	0.780	7
TXLNA	physical association	0.780	7
CFTR	physical association	0.750	4
PRDX3	physical association	0.740	6
NQO2	physical association	0.740	5
CDC23	physical association	0.720	9
MID2	physical association	0.720	7
GABPB2	physical association	0.720	6
MAP1LC3B	physical association	0.720	6
SCAND1	physical association	0.720	6
TRIM38	physical association	0.720	6
CNTNAP2	physical association	0.680	4

BioGRID (564 interactions; top human partners by supporting records): GOLGA2 (Two-hybrid; 13 records), BLZF1 (Affinity Capture-MS; 7 records), TMED2 (Affinity Capture-Western; 5 records), RPIA (Two-hybrid; 4 records), TMED7 (Affinity Capture-MS; 4 records), TRAF2 (Two-hybrid; 4 records), ACY3 (Two-hybrid; 3 records), BEND5 (Two-hybrid; 3 records), C1orf94 (Two-hybrid; 3 records), CBLB (Two-hybrid; 3 records), DCTD (Two-hybrid; 3 records), DPYSL2 (Two-hybrid; 3 records), EIF2B1 (Two-hybrid; 3 records), KCTD9 (Two-hybrid; 3 records), KIF14 (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
MAPK1	unknown	GORASP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 503 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
Long-term potentiation	8	11.3×	1e-04
Tight junction interactions	9	9.8×	1e-04
Unblocking of NMDA receptors, glutamate binding and activation	6	9.7×	3e-03
Neurexins and neuroligins	11	6.4×	3e-04
Ca2+ pathway	12	6.3×	1e-04
EPHB-mediated forward signaling	8	6.3×	4e-03
Assembly and cell surface presentation of NMDA receptors	8	6.0×	4e-03
Neurotransmitter receptors and postsynaptic signal transmission	14	4.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
glutamate receptor signaling pathway	7	14.1×	2e-04
calcium-independent cell-cell adhesion	8	13.8×	4e-05
positive regulation of synaptic transmission, glutamatergic	10	13.4×	4e-06
sodium-independent organic anion transport	5	12.1×	5e-03
prepulse inhibition	5	12.1×	5e-03
regulation of cardiac conduction	6	10.8×	2e-03
positive regulation of excitatory postsynaptic potential	7	7.9×	3e-03
maintenance of blood-brain barrier	7	7.2×	5e-03

Disease & clinical

Genetic variants

Variant evidence for GORASP2: 82 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	5
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 896):

Position(s)	Effect	Δscore	Sites
2:170929405	donor_loss	1.0000	2
2:170948348–170948349	acceptor_loss	1.0000	6
2:170948427	donor_gain	1.0000
2:170949537–170949538	acceptor_loss	1.0000	4
2:170949743–170949744	donor_loss	1.0000	5
2:170950202–170950203	acceptor_loss	1.0000	4
2:170950291–170950292	donor_loss	1.0000	6
2:170951319	acceptor_gain	1.0000
2:170951323	acceptor_gain	1.0000
2:170951459–170951460	donor_loss	1.0000	5

AlphaMissense

1,085 missense substitutions predicted likely pathogenic (of 2,884 scored), across 215 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D38	8	0.999	1.000
D134	8	0.999	1.000
H200	8	0.999	1.000
F37	8	0.997	1.000
H114	8	0.997	1.000
H18	8	0.996	1.000
D148	8	0.990	0.998
D51	8	0.984	0.998
F105	8	0.983	0.999
S99	8	0.980	1.000
D171	8	0.979	0.999
F39	8	0.975	1.000
F102	8	0.970	1.000
F36	8	0.960	1.000
F150	8	0.948	0.999
D140	8	0.945	0.995
S73	8	0.924	1.000
D53	8	0.892	0.987
N111	8	0.843	0.985
S87	8	0.816	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000284
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000345

Disease associations

OMIM: gene MIM:608693 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST000477_50	Cognitive performance	1e-6
GCST012466_1	Autism spectrum disorder	4e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0003926	neuropsychological test

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5483010 (PROTEIN COMPLEX)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases expression	3
bisphenol S	affects expression, decreases methylation, increases expression	3
sodium arsenite	increases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, affects expression	2
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance, affects expression	2
Cyclosporine	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	affects cotreatment, affects expression	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, decreases expression	1
tetrabromobisphenol A	decreases expression	1
monobutyl phthalate	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
2-ethyl-5-carboxypentyl phthalate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
mono(2-ethyl-5-oxohexyl)phthalate	affects cotreatment, decreases expression	1
mono-benzyl phthalate	affects cotreatment, decreases expression, affects expression	1
mono(2-ethyl-5-hydroxyhexyl) phthalate	affects cotreatment, decreases expression, affects expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	decreases phosphorylation	1
mono-isobutyl phthalate	affects cotreatment, decreases expression, affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5383469	Binding	Inhibition of N-terminal GST-tagged GRASP55 (unknown origin) expressed in Escherichia coli BL21 (DE3) cells/JAM-B (unknown origin) complex incubated for 16 hrs by HTRF assay	Discovery of a PDZ Domain Inhibitor Targeting the Syndecan/Syntenin Protein-Protein Interaction: A Semi-Automated “Hit Identification-to-Optimization” Approach. — *J Med Chem*

Cellosaurus cell lines

5 cell lines: 3 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9FQ	Ubigene HEK293 GORASP2 KO	Transformed cell line	Female
CVCL_E3WL	HEK293 GRASP55 KO	Transformed cell line	Female
CVCL_E3WM	HEK293 GRASP55/GRASP65 DKO	Transformed cell line	Female
CVCL_E3WP	HeLa GRASP55 KO	Cancer cell line	Female
CVCL_E3WQ	HeLa GRASP55/GRASP65 DKO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.