GM2A

ganglioside GM2 activator, the group of MD-2 related lipid recognition domain containing

Basic information

Region (hg38): 5:151212150-151270440

Links

ENSG00000196743 ∙ NCBI:2760 ∙ OMIM:613109 ∙ HGNC:4367 ∙ Uniprot:P17900 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tay-Sachs disease AB variant (Definitive), mode of inheritance: AR
• Tay-Sachs disease AB variant (Strong), mode of inheritance: AR
• Tay-Sachs disease AB variant (Strong), mode of inheritance: AR
• Tay-Sachs disease AB variant (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
GM2-gangliosidosis, AB variant	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	Biochemical; Neurologic; Ophthalmologic	5135907; 10364519; 11339652

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GM2A gene.

• Tay-Sachs disease, variant AB (2 variants)
• Tay-Sachs disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GM2A 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			1	23	1	25
missense		2	56	3	4	65
nonsense		1				1
start loss						0
frameshift	2					2
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region			1	8	2	11
non coding		1	45	14	32	92
Total	2	5	102	40	37

Variants in GM2A

This is a list of pathogenic ClinVar variants found in the GM2A region.

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

Position	Type	Phenotype	Significance	ClinVar
5-151223934-G-T		not specified	Uncertain significance (Apr 20, 2024)
5-151223935-T-G		not specified	Uncertain significance (Dec 16, 2022)
5-151252773-C-T			Benign (Jun 21, 2021)
5-151253113-T-C		Tay-Sachs disease, variant AB	Uncertain significance (Jan 12, 2018)
5-151253115-A-G		Tay-Sachs disease, variant AB	Benign (Jun 19, 2021)
5-151253134-C-G		Tay-Sachs disease, variant AB	Uncertain significance (Jan 13, 2018)
5-151253173-G-A		Tay-Sachs disease, variant AB	Benign (Jan 12, 2018)
5-151253210-C-G		Tay-Sachs disease, variant AB	Uncertain significance (Jan 13, 2018)
5-151253220-C-T		Tay-Sachs disease, variant AB	Likely pathogenic (Sep 06, 2021)
5-151253221-A-G		Tay-Sachs disease, variant AB	Uncertain significance (Jul 08, 2022)
5-151253227-T-A		Tay-Sachs disease, variant AB	Uncertain significance (Mar 11, 2022)
5-151253229-A-C		Tay-Sachs disease, variant AB	Uncertain significance (Jun 21, 2022)
5-151253229-A-T		Tay-Sachs disease, variant AB	Uncertain significance (Mar 27, 2022)
5-151253230-T-C		Inborn genetic diseases	Uncertain significance (Apr 08, 2023)
5-151253240-C-T		Tay-Sachs disease, variant AB	Likely benign (Jul 07, 2023)
5-151253249-C-T		Tay-Sachs disease, variant AB • GM2A-related condition	Benign/Likely benign (Oct 13, 2022)
5-151253252-C-T		Tay-Sachs disease, variant AB	Likely benign (Aug 17, 2023)
5-151253253-C-T		Tay-Sachs disease, variant AB	Uncertain significance (Jan 12, 2018)
5-151253255-G-A		Tay-Sachs disease, variant AB	Likely benign (Sep 07, 2022)
5-151253271-G-A		not specified • Tay-Sachs disease, variant AB	Benign (Feb 01, 2024)
5-151253273-C-G		Tay-Sachs disease, variant AB	Likely benign (Jun 23, 2023)
5-151253275-C-T		Inborn genetic diseases	Uncertain significance (Dec 06, 2022)
5-151253294-A-T		Tay-Sachs disease, variant AB	Likely benign (Jan 19, 2024)
5-151253301-A-G		Tay-Sachs disease, variant AB	Uncertain significance (Jul 26, 2022)
5-151253547-C-A			Benign (Jun 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GM2A	protein_coding	protein_coding	ENST00000357164	4	58291

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0310	0.824	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.298	116	107	1.08	0.00000593	1252
Missense in Polyphen		32	34.37	0.93104		436
Synonymous	-1.10	54	44.6	1.21	0.00000255	399
Loss of Function	1.14	3	6.01	0.499	2.53e-7	76

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity (By similarity). Binds gangliosides and stimulates ganglioside GM2 degradation. It stimulates only the breakdown of ganglioside GM2 and glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2 molecules from membranes and presents them in soluble form to beta- hexosaminidase A for cleavage of N-acetyl-D-galactosamine and conversion to GM3. {ECO:0000250}.
• Disease: DISEASE: GM2-gangliosidosis AB (GM2GAB) [MIM:272750]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. It is characterized by GM2 gangliosides accumulation in the presence of both normal hexosaminidase A and B. {ECO:0000269|PubMed:1915858, ECO:0000269|PubMed:8244332, ECO:0000269|PubMed:8900233}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Degradation pathway of sphingolipids, including diseases;Neutrophil degranulation;Metabolism of lipids;Innate Immune System;Immune System;Metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.194

Intolerance Scores

• loftool: 0.376
• rvis_EVS: 0.68
• rvis_percentile_EVS: 84.93

Haploinsufficiency Scores

• pHI: 0.267
• hipred: N
• hipred_score: 0.146
• ghis: 0.404

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.601

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gm2a
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: glycosphingolipid metabolic process;ganglioside catabolic process;lipid transport;learning or memory;oligosaccharide catabolic process;lipid storage;neutrophil degranulation;neuromuscular process controlling balance;positive regulation of hydrolase activity
• Cellular component: extracellular region;cytoplasmic side of plasma membrane;basolateral plasma membrane;apical plasma membrane;azurophil granule lumen;lysosomal lumen;extracellular exosome
• Molecular function: lipid transporter activity;phospholipase activator activity;sphingolipid activator protein activity;beta-N-acetylgalactosaminidase activity