GCC2

protein-coding

GRIP and coiled-coil domain containing 2, the group of Golgins

Gene summary

The protein encoded by this gene is a peripheral membrane protein localized to the trans-Golgi network. It is sensitive to brefeldin A. This encoded protein contains a GRIP domain which is thought to be used in targeting. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

MANE transcript

NM_181453.4

Inheritance

—

ClinVar variants

U:240B:29

Top phenotype

GCC2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:108,449,107-108,509,415

External References & Databases

Ensembl (ENSG00000135968)

Transcript & Mutation Effects

hg38 • Region Span ~60.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GCC2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 234

GCC2-related disorderTotal: 17

not providedTotal: 12

Progressive sensorineural hearing impairmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181453.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	7 clinvar	4 clinvar	13
missense			228 clinvar	14 clinvar	4 clinvar	246
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	240	21	8	269

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181453.4	RefSeq	NP_852118.2	23	MANE Select
ENST00000309863.11	Ensembl	ENSP00000307939.5	23	MANE Select
NM_001410194.1	RefSeq	NP_001397123.1	19	Standard
ENST00000393321.2	Ensembl	ENSP00000376996.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Deregulation of Rab and Rab Effector Genes in Bladder Cancer
Vesicle-mediated transport
Membrane Trafficking
Retrograde transport at the Trans-Golgi-Network
Intra-Golgi and retrograde Golgi-to-ER traffic

Biological Process

protein targeting to lysosome
microtubule organizing center organization
protein localization to Golgi apparatus
microtubule anchoring
late endosome to Golgi transport

Molecular Function

protein binding
identical protein binding

Cellular Component

nucleoplasm
cytoplasm
Golgi apparatus
trans-Golgi network
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309863
Coding exons: 23
Length: 60855
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125747
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.160	791	778	1.02	0.0000386	11149
Missense (PolyPhen)		196	225.78	0.86809		3485
Synonymous	-1.57	316	282	1.12	0.0000141	2864
Loss of Function	6.08	26	87.2	0.298	0.00000443	1203

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.00089	0.00089	rare
East Asian	0.000056	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00020	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Golgin which probably tethers transport vesicles to the trans-Golgi network (TGN) and regulates vesicular transport between the endosomes and the Golgi. As a RAB9A effector it is involved in recycling of the mannose 6-phosphate receptor from the late endosomes to the TGN. May also play a role in transport between the recycling endosomes and the Golgi. Required for maintenance of the Golgi structure, it is involved in the biogenesis of noncentrosomal, Golgi-associated microtubules through recruitment of CLASP1 and CLASP2. {ECO:0000269|PubMed:16885419, ECO:0000269|PubMed:17488291, ECO:0000269|PubMed:17543864}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.871
RVIS EVS: -1.63
RVIS percentile EVS: 2.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.468

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium