GOLGA2

protein-coding

golgin A2, the group of Golgins

Gene summary

The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. This gene encodes one of the golgins, a family of proteins localized to the Golgi. This encoded protein has been postulated to play roles in the stacking of Golgi cisternae and in vesicular transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined. [provided by RefSeq, Feb 2010]

MANE transcript

NM_001366244.2

Inheritance

ClinVar variants

P:11U:170B:57

Top phenotype

Developmental delay with hypotonia, myopathy, and brain abnormalities

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr9:128,255,829-128,276,026

External References & Databases

Ensembl (ENSG00000167110)

Transcript & Mutation Effects

hg38 • Region Span ~20.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental delay with hypotonia, myopathy, and brain abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859375

Submitter: G2P

developmental delay with hypotonia, myopathy, and brain abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859375

Submitter: Labcorp Genetics (formerly Invitae)

developmental delay with hypotonia, myopathy, and brain abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859375

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Developmental delay with hypotonia, myopathy, and brain abnormalitiesAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26742501; 30237576; 34424553

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GOLGA2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 220

not providedTotal: 36

Developmental delay with hypotonia, myopathy, and brain abnormalitiesTotal: 8

GOLGA2-related disorderTotal: 7

Neuromuscular diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001366244.2. 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		1 clinvar	3 clinvar	35 clinvar		39
missense			160 clinvar	22 clinvar		182
nonsense	1 clinvar	2 clinvar	1 clinvar			4
start loss						0
frameshift	6 clinvar					6
splice donor/acceptor (+/-2bp)		1 clinvar	6 clinvar			7
Total	7	4	170	57	0	238

Highest pathogenic variant AF is 0.000006886616

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_001366244.2	RefSeq	NP_001353173.2	27	MANE Select
ENST00000611957.5	Ensembl	ENSP00000478799.2	27	MANE Select
NM_001366246.2	RefSeq	NP_001353175.2	26	Standard
NM_001389695.2	RefSeq	NP_001376624.2	27	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
golga2	Danio rerio	Structure: skeletal muscle Quality: refractivity abnormal

Gene / Model

Organism

Observed Phenotype

golga2

Danio rerio

Structure: skeletal muscle

Quality: refractivity

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models
Neurodegenerative Diseases
Disease
Vesicle-mediated transport
Membrane Trafficking

Biological Process

protein glycosylation
endoplasmic reticulum to Golgi vesicle-mediated transport
microtubule nucleation
Golgi organization
centrosome cycle

Molecular Function

protein binding
microtubule binding
protein kinase binding
syntaxin binding
identical protein binding

Cellular Component

Golgi cis cisterna
Golgi membrane
spindle pole
Golgi apparatus
cis-Golgi network

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000421699
Coding exons: 26
Length: 20167
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.903	520	581	0.895	0.0000359	6495
Missense (PolyPhen)		135	170.51	0.79172		2118
Synonymous	0.906	217	235	0.925	0.0000143	1899
Loss of Function	5.98	11	61.7	0.178	0.00000292	702

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00020	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane (Probable) (PubMed:16489344). Required for normal protein transport from the endoplasmic reticulum to the Golgi apparatus and the cell membrane (By similarity). Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401). {ECO:0000250|UniProtKB:Q62839, ECO:0000250|UniProtKB:Q921M4, ECO:0000269|PubMed:16489344, ECO:0000269|PubMed:17314401, ECO:0000269|PubMed:18045989, ECO:0000269|PubMed:19109421, ECO:0000269|PubMed:19242490, ECO:0000269|PubMed:26165940, ECO:0000305|PubMed:26363069}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.438
RVIS EVS: 0.36
RVIS percentile EVS: 74.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.727

Gene Damage Prediction

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