GCC1

Summary

GCC1 (GRIP and coiled-coil domain containing 1, HGNC:19095) is a protein-coding gene on chromosome 7q32.1, encoding GRIP and coiled-coil domain-containing protein 1 (Q96CN9). Probably involved in maintaining Golgi structure.

The protein encoded by this gene is a peripheral membrane protein. It is sensitive to brefeldin A. This encoded protein contains a GRIP domain which is thought to be used in targeting. It may play a role in the organization of trans-Golgi network subcompartment involved with membrane transport.

Source: NCBI Gene 79571 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_024523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19095
Approved symbol	GCC1
Name	GRIP and coiled-coil domain containing 1
Location	7q32.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22035, GCC88, GCC1P, MGC20706
Ensembl gene	ENSG00000179562
Ensembl biotype	protein_coding
OMIM	607418
Entrez	79571

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000321407, ENST00000473728, ENST00000497650

RefSeq mRNA: 1 — MANE Select: NM_024523 NM_024523

CCDS: CCDS5796

Canonical transcript exons

ENST00000321407 — 2 exons

Exon	Start	End
ENSE00001262450	127580628	127583309
ENSE00001262454	127584151	127585596

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 85.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8855 / max 91.6704, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86032	12.8765	1803
86034	0.0090	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	85.53	gold quality
islet of Langerhans	UBERON:0000006	83.47	gold quality
granulocyte	CL:0000094	83.43	gold quality
stromal cell of endometrium	CL:0002255	83.41	gold quality
blood	UBERON:0000178	83.17	gold quality
right testis	UBERON:0004534	81.89	gold quality
left testis	UBERON:0004533	81.40	gold quality
testis	UBERON:0000473	81.14	gold quality
sperm	CL:0000019	81.12	gold quality
male germ cell	CL:0000015	80.89	gold quality
nipple	UBERON:0002030	80.87	gold quality
upper leg skin	UBERON:0004262	80.83	gold quality
tongue squamous epithelium	UBERON:0006919	80.80	silver quality
gingival epithelium	UBERON:0001949	80.77	gold quality
leukocyte	CL:0000738	80.68	gold quality
bone marrow	UBERON:0002371	80.49	gold quality
monocyte	CL:0000576	80.32	gold quality
gingiva	UBERON:0001828	80.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.23	gold quality
mononuclear cell	CL:0000842	80.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.19	gold quality
amniotic fluid	UBERON:0000173	80.09	gold quality
squamous epithelium	UBERON:0006914	79.84	gold quality
tonsil	UBERON:0002372	79.70	gold quality
bone marrow cell	CL:0002092	79.63	gold quality
layer of synovial tissue	UBERON:0007616	79.14	gold quality
penis	UBERON:0000989	79.05	gold quality
mucosa of transverse colon	UBERON:0004991	79.05	gold quality
epithelium of esophagus	UBERON:0001976	78.95	gold quality
esophagus squamous epithelium	UBERON:0006920	78.95	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	111.93
E-ANND-3	no	3.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting GCC1, 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-188-3P	100.00	68.76	1240
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306

Literature-anchored findings (GeneRIF, showing 7)

• targeting to subcompartments of trans-Golgi network by GRIP domain (PMID:12446665)
• The ability of the four mammalian GRIP domain proteins, p230, golgin-97, GCC88, and GCC185 to interact is reported. (PMID:15654769)
• identified an essential role for GCC88 in the localization of TGN fusion machinery for transport from early endosomes to the trans-Golgi network (PMID:17914056)
• the long isoform of intersectin-1 (ITSN-1), a guanine nucleotide exchange factor for Cdc42, is identified as a novel Golgi component and an interaction partner of GCC88 responsible for mediating the actin-dependent dispersal of the Golgi ribbon. (PMID:30540523)
• The authors show that GCC88 is required for the maintenance of the trans-Golgi network (TGN) structure and the efficient endosome-to-TGN trafficking of the cation-independent mannose 6-phosphate receptor (CI-M6PR). (PMID:30791178)
• Spatial proteomics defines the content of trafficking vesicles captured by golgin tethers. (PMID:33239640)
• Golgi-58K can re-localize to late endosomes upon cellular uptake of PS-ASOs and facilitates endosomal release of ASOs. (PMID:34244781)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gcc1	ENSDARG00000045541
mus_musculus	Gcc1	ENSMUSG00000029708
rattus_norvegicus	Gcc1	ENSRNOG00000007792
drosophila_melanogaster	GCC88	FBGN0037881
caenorhabditis_elegans		WBGENE00011503

Paralogs (1): GOLGA1 (ENSG00000136935)

Protein

Protein identifiers

GRIP and coiled-coil domain-containing protein 1 — Q96CN9 (reviewed: Q96CN9)

Alternative names: Golgi coiled-coil protein 1

All UniProt accessions (2): A4D0Z4, Q96CN9

UniProt curated annotations — full annotation on UniProt →

Function. Probably involved in maintaining Golgi structure.

Subcellular location. Cytoplasm. Golgi apparatus membrane.

Domain organisation. Extended rod-like protein with coiled-coil domains.

RefSeq proteins (1): NP_078799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000237	GRIP_dom	Domain
IPR051952	Golgi-autophagy_related	Family

Pfam: PF01465

UniProt features (16 total): sequence variant 6, compositionally biased region 4, region of interest 2, coiled-coil region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CN9-F1	78.42	0.51

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network

MSigDB gene sets: 101 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, BENPORATH_ES_WITH_H3K27ME3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, BLALOCK_ALZHEIMERS_DISEASE_UP, GTGTTGA_MIR505, chr7q32, TGGNNNNNNKCCAR_UNKNOWN, GOCC_GOLGI_STACK, GOCC_GOLGI_CISTERNA, GOCC_ORGANELLE_SUBCOMPARTMENT, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, P53_02, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B

GO Biological Process (0):

GO Molecular Function (2): small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (6): Golgi trans cisterna (GO:0000138), Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
GTPase binding	1
binding	1
Golgi cisterna	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCC1	GOLGA4	Q13439	920
GCC1	GRIP1	Q9Y3R0	913
GCC1	ITSN1	Q15811	891
GCC1	TGOLN2	O43493	862
GCC1	GOLGA1	Q92805	720
GCC1	RAB6A	P20340	693
GCC1	GCC2	Q8IWJ2	633
GCC1	R3HDML	Q9H3Y0	609
GCC1	IGF2R	P11717	592
GCC1	GUCA2B	Q16661	591
GCC1	GOLGA2	Q08379	589
GCC1	KCNK16	Q96T55	583
GCC1	MAEA	Q7L5Y9	571
GCC1	ZFAND3	Q9H8U3	570
GCC1	GORASP1	Q9BQQ3	570

IntAct

228 interactions, top by confidence:

A	B	Type	Score
CEP57	GCC1	psi-mi:“MI:0915”(physical association)	0.740
GCC1	CEP57	psi-mi:“MI:0915”(physical association)	0.740
ATF4	GCC1	psi-mi:“MI:0915”(physical association)	0.720
GCC1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
BIRC2	GCC1	psi-mi:“MI:0915”(physical association)	0.720
CEP70	GCC1	psi-mi:“MI:0915”(physical association)	0.720
GCC1	ATF4	psi-mi:“MI:0915”(physical association)	0.720
GCC1	CEP70	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	GCC1	psi-mi:“MI:0915”(physical association)	0.720
GCC1	ABI2	psi-mi:“MI:0915”(physical association)	0.670
ABI2	GCC1	psi-mi:“MI:0915”(physical association)	0.670
LNPEP	CANX	psi-mi:“MI:0914”(association)	0.640
MCRS1	GCC1	psi-mi:“MI:0915”(physical association)	0.620
GCC1	MCRS1	psi-mi:“MI:0915”(physical association)	0.620
OIP5	GCC1	psi-mi:“MI:0915”(physical association)	0.560
ZNF276	GCC1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (145): GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), GCC1 (Two-hybrid), CEP70 (Two-hybrid), LZTS2 (Two-hybrid)

ESM2 similar proteins: A0A2R8QCI3, A0JMK8, A3KGV1, A7YH32, A9X1A5, B0KWC9, B6MFW3, B8JK76, G5E861, G9G127, O35550, O35551, P59242, P85120, Q15276, Q3V6T2, Q502I3, Q5BJF6, Q5RG45, Q5SNZ0, Q5TZ80, Q5ZJ27, Q5ZKK5, Q66GS9, Q66KE8, Q6AYX5, Q6DIX6, Q6NRB0, Q6P402, Q6P5D4, Q6PGZ0, Q6VGS5, Q6ZU80, Q7TMK6, Q80UF4, Q80YF0, Q80YT7, Q86SQ7, Q8BIL5, Q8CJ99

Diamond homologs: D3ZZL9, O14715, P0DJD0, P0DJD1, Q8CHG3, Q8IWJ2, Q96CN9, Q99666, Q9D4H2, Q7Z3J3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GCC1	“up-regulates activity”	ITSN1	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

673 predictions. Top by Δscore:

Variant	Effect	Δscore
7:127583306:CTGT:C	acceptor_gain	1.0000
7:127583310:C:CC	acceptor_gain	1.0000
7:127584148:TA:T	donor_loss	1.0000
7:127584150:C:CT	donor_loss	1.0000
7:127584150:CCTTT:C	donor_gain	1.0000
7:127584209:T:TA	donor_gain	1.0000
7:127589081:A:AG	acceptor_gain	1.0000
7:127589081:AGTT:A	acceptor_gain	1.0000
7:127589082:G:GG	acceptor_gain	1.0000
7:127589082:GTT:G	acceptor_gain	1.0000
7:127589082:GTTG:G	acceptor_gain	1.0000
7:127589163:GGTGA:G	donor_loss	1.0000
7:127589164:G:GA	donor_loss	1.0000
7:127589165:T:A	donor_loss	1.0000
7:127589473:A:AG	acceptor_gain	1.0000
7:127589474:A:G	acceptor_gain	1.0000
7:127589477:A:AG	acceptor_gain	1.0000
7:127589482:CA:C	acceptor_loss	1.0000
7:127589483:A:AG	acceptor_gain	1.0000
7:127589484:G:GT	acceptor_gain	1.0000
7:127589484:GGC:G	acceptor_gain	1.0000
7:127590059:T:A	acceptor_gain	1.0000
7:127590061:CCCA:C	acceptor_loss	1.0000
7:127590063:CA:C	acceptor_loss	1.0000
7:127590064:A:AG	acceptor_gain	1.0000
7:127590064:AG:A	acceptor_gain	1.0000
7:127590064:AGG:A	acceptor_gain	1.0000
7:127590065:G:GG	acceptor_gain	1.0000
7:127590065:GG:G	acceptor_gain	1.0000
7:127590065:GGG:G	acceptor_gain	1.0000

AlphaMissense

5066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:127582171:T:A	K724I	1.000
7:127582854:C:A	K496N	1.000
7:127582854:C:G	K496N	1.000
7:127582170:T:A	K724N	0.999
7:127582170:T:G	K724N	0.999
7:127582177:T:C	Y722C	0.999
7:127582178:A:G	Y722H	0.999
7:127582856:T:C	K496E	0.999
7:127582879:A:G	L488P	0.999
7:127582888:A:G	L485P	0.999
7:127582105:A:T	I746K	0.998
7:127582108:G:T	A745D	0.998
7:127582174:A:G	L723P	0.998
7:127582846:G:T	A499D	0.998
7:127582859:A:C	Y495D	0.998
7:127582866:A:C	F492L	0.998
7:127582866:A:T	F492L	0.998
7:127582868:A:G	F492L	0.998
7:127583140:A:G	L401P	0.998
7:127582105:A:C	I746R	0.997
7:127582171:T:G	K724T	0.997
7:127582172:T:C	K724E	0.997
7:127582177:T:G	Y722S	0.997
7:127582178:A:C	Y722D	0.997
7:127582855:T:A	K496M	0.997
7:127582867:A:G	F492S	0.997
7:127583161:A:G	L394P	0.997
7:127584476:C:G	R236P	0.997
7:127584659:A:T	V175D	0.997
7:127585049:A:G	L45P	0.997

dbSNP variants (sampled 300 via entrez): RS1000402305 (7:127584548 T>A,C), RS1001030731 (7:127585638 G>A,T), RS1001082739 (7:127585779 A>C,G,T), RS1001203478 (7:127580975 T>A), RS1001426199 (7:127587445 A>C), RS1001562831 (7:127585721 G>T), RS1002516682 (7:127587065 G>A), RS1002952037 (7:127582360 G>A), RS1003152787 (7:127583884 A>C,G), RS1003185293 (7:127583567 A>C,G), RS1004350943 (7:127583598 C>T), RS1005224417 (7:127583545 T>G), RS1005418490 (7:127585409 C>A), RS1005831304 (7:127580367 T>G), RS1006370805 (7:127586536 C>T)

Disease associations

OMIM: gene MIM:607418 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001351_2	Type 2 diabetes	5.000000e-11
GCST002637_1	Medication adherence in chronic diseases	5.000000e-07
GCST003400_38	Type 2 diabetes	3.000000e-07
GCST005316_12	Intelligence (MTAG)	2.000000e-09
GCST005316_449	Intelligence (MTAG)	4.000000e-08
GCST006269_1152	General cognitive ability	2.000000e-08
GCST006950_16	Feeling worry	1.000000e-08
GCST007847_114	Type 2 diabetes	1.000000e-08
GCST007847_31	Type 2 diabetes	4.000000e-74
GCST010002_263	Refractive error	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006344	medication adherence behavior
EFO:0004337	intelligence
EFO:0009589	worry measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects expression, increases abundance	2
Cisplatin	increases expression	2
Tunicamycin	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
entinostat	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cannabinoids	increases expression	1
Cocaine	increases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	affects expression	1

Clinical trials (associated diseases)

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