GOLGA2

golgin A2, the group of Golgins

Basic information

Region (hg38): 9:128255829-128276026

Links

ENSG00000167110 ∙ NCBI:2801 ∙ OMIM:602580 ∙ HGNC:4425 ∙ Uniprot:Q08379 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental delay with hypotonia, myopathy, and brain abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental delay with hypotonia, myopathy, and brain abnormalities	AR	General	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	Craniofacial; Musculoskeletal; Neurologic	26742501; 30237576; 34424553

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GOLGA2 gene.

• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GOLGA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6		6
missense			54	7	1	62
nonsense	2	1				3
start loss						0
frameshift	2					2
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding					1	1
Total	4	2	55	13	3

Highest pathogenic variant AF is 0.00000657

Variants in GOLGA2

This is a list of pathogenic ClinVar variants found in the GOLGA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-128257129-G-C		not specified	Uncertain significance (Oct 08, 2024)
9-128257150-G-A		not specified	Uncertain significance (Sep 12, 2023)
9-128257159-G-A		not specified	Uncertain significance (Jun 22, 2021)
9-128257159-G-C		not specified	Uncertain significance (Aug 08, 2023)
9-128257160-G-A			Likely benign (Oct 01, 2022)
9-128257173-C-T		not specified	Uncertain significance (Feb 16, 2023)
9-128257258-C-T		not specified	Uncertain significance (Jul 22, 2024)
9-128257261-C-G		not specified	Uncertain significance (Nov 09, 2024)
9-128257276-A-T		not specified	Uncertain significance (Aug 12, 2024)
9-128257383-G-A			Uncertain significance (Aug 01, 2017)
9-128257399-G-C		not specified	Uncertain significance (Oct 20, 2023)
9-128257402-G-A		not specified	Uncertain significance (Nov 25, 2024)
9-128257444-C-T		not specified	Uncertain significance (Jun 02, 2023)
9-128257454-G-C		not specified	Uncertain significance (Apr 24, 2024)
9-128257465-G-A		not specified	Likely benign (Feb 16, 2023)
9-128257525-C-T		not specified	Uncertain significance (Jan 25, 2023)
9-128257599-A-G			Likely pathogenic (Jul 05, 2022)
9-128257686-T-C		not specified	Uncertain significance (Dec 28, 2022)
9-128257863-C-G		not specified	Uncertain significance (Mar 29, 2024)
9-128258012-G-A		not specified	Uncertain significance (Mar 08, 2024)
9-128258017-G-T		not specified	Uncertain significance (Sep 20, 2024)
9-128258042-C-T		not specified	Uncertain significance (Jul 14, 2024)
9-128258048-C-T		not specified	Likely benign (Jan 03, 2024)
9-128258051-G-A		not specified	Uncertain significance (Feb 21, 2024)
9-128258072-G-C		not specified	Uncertain significance (Nov 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GOLGA2	protein_coding	protein_coding	ENST00000421699	26	20167

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.988	0.0124	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.903	520	581	0.895	0.0000359	6495
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000226	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000172	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.000172	0.000163
South Asian	0.000198	0.000163
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Golgi Cisternae Pericentriolar Stack Reorganization;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Mitotic Prophase;COPI-mediated anterograde transport;M Phase;Cell Cycle;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport;Cell Cycle, Mitotic;PLK1 signaling events (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.438
• rvis_EVS: 0.36
• rvis_percentile_EVS: 74.7

Haploinsufficiency Scores

• pHI: 0.135
• hipred: Y
• hipred_score: 0.546
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.727

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Golga2

Zebrafish Information Network

• Gene name: golga2
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: refractivity

Gene ontology

• Biological process: protein glycosylation;endoplasmic reticulum to Golgi vesicle-mediated transport;microtubule nucleation;Golgi organization;centrosome cycle;asymmetric cell division;negative regulation of autophagy;protein transport;negative regulation of protein binding;COPII vesicle coating;spindle assembly;protein homotetramerization;positive regulation of protein glycosylation;Golgi ribbon formation;Golgi disassembly;spindle assembly involved in meiosis;mitotic spindle assembly;positive regulation of ubiquitin protein ligase activity
• Cellular component: Golgi cis cisterna;Golgi membrane;spindle pole;Golgi apparatus;cis-Golgi network;microtubule;COPII-coated ER to Golgi transport vesicle;Golgi cisterna membrane;endoplasmic reticulum-Golgi intermediate compartment membrane;mitotic spindle
• Molecular function: protein binding;microtubule binding;protein kinase binding;syntaxin binding;identical protein binding;cadherin binding;importin-alpha family protein binding