GM2A

Summary

GM2A (ganglioside GM2 activator, HGNC:4367) is a protein-coding gene on chromosome 5q33.1, encoding Ganglioside GM2 activator (P17900). The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity.

This gene encodes a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal enzyme beta-hexosaminidase A. Beta-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene result in GM2-gangliosidosis type AB or the AB variant of Tay-Sachs disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2760 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tay-Sachs disease AB variant (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 237 total — 8 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 40
• MANE Select transcript: NM_000405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4367
Approved symbol	GM2A
Name	ganglioside GM2 activator
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	SAP-3, GM2-AP, GM2AP
Ensembl gene	ENSG00000196743
Ensembl biotype	protein_coding
OMIM	613109
Entrez	2760

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000357164, ENST00000523004, ENST00000523466, ENST00000937902

RefSeq mRNA: 2 — MANE Select: NM_000405 NM_000405, NM_001167607

CCDS: CCDS4313

Canonical transcript exons

ENST00000357164 — 4 exons

Exon	Start	End
ENSE00001085753	151253185	151253297
ENSE00001085757	151266731	151266913
ENSE00001328369	151259755	151259916
ENSE00001427604	151267296	151270440

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 251.9751 / max 7203.9331, expressed in 1819 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59607	217.5325	1802
59608	11.4406	1756
59605	10.9943	1750
59606	7.1036	1640
59603	1.8325	1050
59604	1.3981	886
59592	0.6770	131
59611	0.6028	168
59612	0.3466	114
59593	0.0473	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mammalian vulva	UBERON:0000997	98.76	gold quality
penis	UBERON:0000989	98.61	gold quality
placenta	UBERON:0001987	97.34	gold quality
cervix epithelium	UBERON:0004801	96.89	gold quality
cervix squamous epithelium	UBERON:0006922	96.82	gold quality
esophagus squamous epithelium	UBERON:0006920	96.75	gold quality
gingiva	UBERON:0001828	96.59	gold quality
squamous epithelium	UBERON:0006914	96.57	gold quality
epithelium of esophagus	UBERON:0001976	96.51	gold quality
gingival epithelium	UBERON:0001949	96.40	gold quality
upper leg skin	UBERON:0004262	96.17	gold quality
nipple	UBERON:0002030	96.12	gold quality
skin of hip	UBERON:0001554	95.86	gold quality
tongue squamous epithelium	UBERON:0006919	95.66	gold quality
inferior vagus X ganglion	UBERON:0005363	95.32	gold quality
monocyte	CL:0000576	95.30	gold quality
periodontal ligament	UBERON:0008266	95.30	gold quality
mononuclear cell	CL:0000842	95.10	gold quality
leukocyte	CL:0000738	94.87	gold quality
esophagus mucosa	UBERON:0002469	94.45	gold quality
epithelium of nasopharynx	UBERON:0001951	94.10	gold quality
lymph node	UBERON:0000029	94.01	gold quality
spinal cord	UBERON:0002240	93.99	gold quality
decidua	UBERON:0002450	93.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.99	gold quality
visceral pleura	UBERON:0002401	93.97	gold quality
subthalamic nucleus	UBERON:0001906	93.91	gold quality
middle frontal gyrus	UBERON:0002702	93.90	gold quality
amniotic fluid	UBERON:0000173	93.86	gold quality
skin of abdomen	UBERON:0001416	93.86	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	75.03
E-HCAD-13	yes	24.19
E-ANND-3	yes	11.25
E-MTAB-9067	yes	11.21
E-MTAB-9801	yes	6.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SP1

miRNA regulators (miRDB)

90 targeting GM2A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3913-5P	99.78	67.26	968

Literature-anchored findings (GeneRIF, showing 16)

• GM2 activator protein exerts strong and broad inhibitory effects on the hydrolysis of phospholipids carried out by plant and microbial phospholipases D (PMID:12576516)
• Two new structures of GM2-AP with bound lipids, showing two different lipid-binding modes within the apolar pocket (PMID:12909021)
• elucidation of mode of action on gangioside GM2 (PMID:14728689)
• alpha-subunit loop structure is required for GM2 activator protein binding by beta-hexosaminidase A (PMID:15485660)
• glycosphingolipids, particularly GM2, form a complex with CD82, and this complex interacts with Met and thereby inhibits HGF-induced Met tyrosine kinase activity, as well as integrin to Met cross-talk (PMID:17215249)
• these results provide novel insights into the physiological functions of GM2AP in obesity. (PMID:21036149)
• Treatment of meniscal explants with IL-1RA inhibited the expression of many catabolic genes following a single bout of high dynamic strain. (PMID:21331553)
• impact of GM2AP on glucose metabolism (PMID:21784073)
• In vitro assays with the isolated H1 or H2 homodimers (beta-alpha hybrid construct of beta-hexosaminidase A subunits) confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside. (PMID:23483939)
• Gene polymorphisms of MD2 and GM2A were associated with the occurrence or severity of neonatal necrotizing enterocolitis. (PMID:25816011)
• Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies (PMID:26175473)
• this study has established the potential role of GM2A in breast cancer progression (PMID:27002480)
• Studies indicate that sphingolipid activator proteins (SAPs) and anionic lipids are essential stimulators to reach physiological rates of lysosomal sphingolipid degradation. (PMID:27157270)
• Review of GM2A mutations causing GM2 activator protein deficiency and GM2 gangliosidosis-AB variant. (PMID:27402091)
• GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells. (PMID:31578452)
• Two patients from Turkey with a novel variant in the GM2A gene and review of the literature. (PMID:33819415)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gm2a	ENSDARG00000088439
danio_rerio	GM2A	ENSDARG00000107431
mus_musculus	Gm2a	ENSMUSG00000000594
rattus_norvegicus	Gm2a	ENSRNOG00000052219

Protein

Protein identifiers

Ganglioside GM2 activator — P17900 (reviewed: P17900)

Alternative names: Cerebroside sulfate activator protein, GM2-AP, Sphingolipid activator protein 3

All UniProt accessions (3): E5RJD0, P17900, H0YBY3

UniProt curated annotations — full annotation on UniProt →

Function. The large binding pocket can accommodate several single chain phospholipids and fatty acids, GM2A also exhibits some calcium-independent phospholipase activity. 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. Has cholesterol transfer activity.

Subcellular location. Lysosome.

Post-translational modifications. The serines in positions 32 and 33 are absent in 80% of the sequenced protein.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (2): NP_000396, NP_001161079 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003172	ML_dom	Domain
IPR028996	GM2-AP	Family
IPR036846	GM2-AP_sf	Homologous_superfamily

Pfam: PF02221

Catalyzed reactions (Rhea), 1 shown:

• cholesterol(in) = cholesterol(out) (RHEA:39747)

UniProt features (31 total): strand 11, sequence variant 6, disulfide bond 4, turn 2, chain 2, helix 2, signal peptide 1, propeptide 1, sequence conflict 1, glycosylation site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
2AG4	X-RAY DIFFRACTION	1.8
1PU5	X-RAY DIFFRACTION	1.9
1G13	X-RAY DIFFRACTION	2
1TJJ	X-RAY DIFFRACTION	2
2AF9	X-RAY DIFFRACTION	2
2AG2	X-RAY DIFFRACTION	2
2AG9	X-RAY DIFFRACTION	2.2
1PUB	X-RAY DIFFRACTION	2.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17900-F1	89.10	0.72

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (4): 39–183, 99–106, 112–138, 125–136

Glycosylation sites (1): 63

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 424 (showing top): GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, GOBP_BEHAVIOR, GOCC_SECRETORY_GRANULE, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_OLIGOSACCHARIDE_CATABOLIC_PROCESS, KEGG_LYSOSOME, AMIT_SERUM_RESPONSE_40_MCF10A, WIELAND_UP_BY_HBV_INFECTION, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE

GO Biological Process (11): ganglioside catabolic process (GO:0006689), lipid transport (GO:0006869), learning or memory (GO:0007611), oligosaccharide catabolic process (GO:0009313), lipid storage (GO:0019915), glycosphingolipid catabolic process (GO:0046479), neuromuscular process controlling balance (GO:0050885), ganglioside metabolic process (GO:0001573), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), nervous system process (GO:0050877)

GO Molecular Function (8): lipid carrier activity (GO:0005319), phospholipase activator activity (GO:0016004), sphingolipid activator protein activity (GO:0030290), beta-N-acetylgalactosaminidase activity (GO:0032428), beta-N-acetylhexosaminidase activity (GO:0004563), protein binding (GO:0005515), enzyme activator activity (GO:0008047), hydrolase activity (GO:0016787)

GO Cellular Component (10): extracellular region (GO:0005576), cytosol (GO:0005829), cytoplasmic side of plasma membrane (GO:0009898), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), lysosome (GO:0005764), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Innate Immune System	1
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Immune System	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
glycosphingolipid metabolic process	2
catalytic activity	2
plasma membrane region	2
vacuolar lumen	2
ganglioside metabolic process	1
glycosphingolipid catabolic process	1
ceramide catabolic process	1
transport	1
lipid localization	1
behavior	1
cognition	1
oligosaccharide metabolic process	1
carbohydrate catabolic process	1
nutrient storage	1
glycolipid catabolic process	1
sphingolipid catabolic process	1
musculoskeletal movement	1
neuromuscular process	1
ceramide metabolic process	1
primary metabolic process	1
lipid metabolic process	1
system process	1
molecular carrier activity	1
glycerophospholipase activity	1
lipase activator activity	1
enzyme activator activity	1
beta-N-acetylhexosaminidase activity	1
hexosaminidase activity	1
binding	1
enzyme regulator activity	1
molecular function activator activity	1
cytoplasm	1
plasma membrane	1
cytoplasmic side of membrane	1
basal plasma membrane	1
apical part of cell	1
secretory granule lumen	1
azurophil granule	1
lysosome	1

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GM2A	ETFA	P13804	931
GM2A	OGA	O60502	857
GM2A	HEXB	P07686	813
GM2A	HMGB3	O15347	650
GM2A	PSAP	P07292	638
GM2A	GALNS	P34059	566
GM2A	MAN2B1	O00754	553
GM2A	SORT1	Q99523	518
GM2A	NPC2	P61916	505
GM2A	ENC1	O14682	492
GM2A	HEXA	P06865	478
GM2A	ASAH1	Q13510	474
GM2A	ARSA	P15289	473
GM2A	CLN8	Q9UBY8	470
GM2A	PPP6C	O00743	468

IntAct

82 interactions, top by confidence:

A	B	Type	Score
POC5	CETN3	psi-mi:“MI:0914”(association)	0.920
POC5	CETN3	psi-mi:“MI:0914”(association)	0.770
GID8	PGRMC2	psi-mi:“MI:0914”(association)	0.640
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
CFAP298	PEX7	psi-mi:“MI:0914”(association)	0.620
GM2A	ACTA2	psi-mi:“MI:0915”(physical association)	0.590
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
GMCL1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
CCDC51	TGM5	psi-mi:“MI:0914”(association)	0.530
KIR3DS1	PPL	psi-mi:“MI:0914”(association)	0.530
AIRE	ALOX12B	psi-mi:“MI:0914”(association)	0.530
SSBP4	GM2A	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530
SF3A1	DNAJC8	psi-mi:“MI:0914”(association)	0.530
GM2A	GNB2	psi-mi:“MI:0915”(physical association)	0.400
ECH1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PDE4DIP	A2ML1	psi-mi:“MI:0914”(association)	0.350
DDX19B	IGLL5	psi-mi:“MI:0914”(association)	0.350
HSF2	IMPA2	psi-mi:“MI:0914”(association)	0.350
ZIC1	IMPA2	psi-mi:“MI:0914”(association)	0.350
VNN2	ATP2A1	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Proximity Label-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS), GM2A (Affinity Capture-MS)

ESM2 similar proteins: A5A6I6, A6QP57, B0FHH8, O02380, O93429, O94183, O97763, P02787, P02789, P05090, P08071, P09571, P0CP28, P0CP29, P12346, P17900, P19134, P23593, P27425, P31729, P49278, P51910, P61916, P61917, P61918, P79345, P79815, P79819, P80384, P80426, P80429, Q08188, Q25481, Q28895, Q29290, Q29443, Q336T5, Q4X136, Q52FS9, Q60648

Diamond homologs: P17900, Q60648, Q8HXX6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	9
Uncertain significance	117
Likely benign	57
Benign	38

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
100728	NM_000405.5(GM2A):c.333del (p.Cys112fs)	Pathogenic
1699419	NM_000405.5(GM2A):c.209del (p.Gly70fs)	Pathogenic
3340369	NM_000405.5(GM2A):c.259G>T (p.Glu87Ter)	Pathogenic
390	NM_000405.5(GM2A):c.412T>C (p.Cys138Arg)	Pathogenic
391	NM_000405.5(GM2A):c.506G>C (p.Arg169Pro)	Pathogenic
393	NM_000405.5(GM2A):c.410del (p.His137fs)	Pathogenic
394	NM_000405.5(GM2A):c.160G>T (p.Glu54Ter)	Pathogenic
529236	NC_000005.10:g.(?151253197)(151267660_?)del	Pathogenic
1305434	NM_000405.5(GM2A):c.367del (p.Glu123fs)	Likely pathogenic
1324484	NM_000405.5(GM2A):c.4C>T (p.Gln2Ter)	Likely pathogenic
2584380	NM_000405.5(GM2A):c.364G>A (p.Gly122Arg)	Likely pathogenic
2664353	NM_000405.5(GM2A):c.427-14T>A	Likely pathogenic
3591900	NM_000405.5(GM2A):c.226_227del (p.Leu76fs)	Likely pathogenic
375272	NM_000405.5(GM2A):c.244-2A>T	Likely pathogenic
375273	NM_000405.5(GM2A):c.472G>T (p.Glu158Ter)	Likely pathogenic
624073	NM_000405.5(GM2A):c.413G>A (p.Cys138Tyr)	Likely pathogenic
976256	NM_000405.5(GM2A):c.262_264del (p.Lys88del)	Likely pathogenic

SpliceAI

705 predictions. Top by Δscore:

Variant	Effect	Δscore
5:151253294:AAAGG:A	donor_loss	1.0000
5:151253295:AAGGT:A	donor_loss	1.0000
5:151253296:AGGT:A	donor_loss	1.0000
5:151253298:G:C	donor_loss	1.0000
5:151259735:T:TA	acceptor_gain	1.0000
5:151259738:T:A	acceptor_gain	1.0000
5:151259742:T:A	acceptor_gain	1.0000
5:151259914:AAGG:A	donor_loss	1.0000
5:151259915:AGGTG:A	donor_loss	1.0000
5:151259916:GGTGA:G	donor_loss	1.0000
5:151259917:G:T	donor_loss	1.0000
5:151259918:T:G	donor_loss	1.0000
5:151266727:C:G	acceptor_gain	1.0000
5:151266727:CCA:C	acceptor_loss	1.0000
5:151266730:G:A	acceptor_loss	1.0000
5:151266909:AAGAA:A	donor_gain	1.0000
5:151266910:AGAA:A	donor_gain	1.0000
5:151266911:GAA:G	donor_gain	1.0000
5:151266911:GAAG:G	donor_gain	1.0000
5:151266912:AAG:A	donor_loss	1.0000
5:151266914:G:GG	donor_gain	1.0000
5:151266914:G:T	donor_loss	1.0000
5:151266915:T:A	donor_loss	1.0000
5:151267488:G:GT	donor_gain	1.0000
5:151267489:A:T	donor_gain	1.0000
5:151223917:CTTTA:C	donor_loss	0.9900
5:151223918:TTTAC:T	donor_loss	0.9900
5:151223919:TTACC:T	donor_loss	0.9900
5:151223920:TAC:T	donor_loss	0.9900
5:151223921:A:T	donor_loss	0.9900

AlphaMissense

1257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:151266769:G:C	W94C	0.992
5:151266769:G:T	W94C	0.992
5:151267371:T:G	Y168D	0.991
5:151266803:T:A	C106S	0.989
5:151266804:G:C	C106S	0.989
5:151266899:T:A	C138S	0.989
5:151266899:T:C	C138R	0.989
5:151266900:G:C	C138S	0.989
5:151266822:G:A	C112Y	0.988
5:151266860:T:C	C125R	0.988
5:151266893:T:C	C136R	0.988
5:151259781:G:C	W36C	0.987
5:151259781:G:T	W36C	0.987
5:151266860:T:A	C125S	0.987
5:151266861:G:C	C125S	0.987
5:151266893:T:A	C136S	0.987
5:151266894:G:C	C136S	0.987
5:151266821:T:A	C112S	0.986
5:151266822:G:C	C112S	0.986
5:151267375:G:C	R169P	0.986
5:151259779:T:A	W36R	0.985
5:151259779:T:C	W36R	0.985
5:151266800:A:C	S105R	0.985
5:151266802:C:A	S105R	0.985
5:151266802:C:G	S105R	0.985
5:151267365:G:T	G166W	0.985
5:151266821:T:C	C112R	0.984
5:151267416:T:A	C183S	0.984
5:151267417:G:C	C183S	0.984
5:151266894:G:A	C136Y	0.983

dbSNP variants (sampled 300 via entrez): RS1000010367 (5:151258784 G>A,C), RS1000125190 (5:151252403 G>A), RS1000221874 (5:151251655 T>A,G), RS1000251866 (5:151265047 A>T), RS1000367099 (5:151257801 T>C), RS1000482978 (5:151258029 G>A), RS1000717108 (5:151270488 G>A), RS1000720033 (5:151269922 C>T), RS1001013645 (5:151264527 G>A), RS1001329367 (5:151261862 C>T), RS1001402253 (5:151267789 A>G), RS1001579048 (5:151257050 A>G), RS1001683673 (5:151257365 T>C), RS1001904067 (5:151262583 C>T), RS1001917369 (5:151255607 G>A)

Disease associations

OMIM: gene MIM:613109 | disease phenotypes: MIM:272750, MIM:272800

GenCC curated gene-disease

Disease	Classification	Inheritance
Tay-Sachs disease AB variant	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Tay-Sachs disease AB variant	Definitive	AR

Mondo (2): Tay-Sachs disease AB variant (MONDO:0010099), Tay-Sachs disease (MONDO:0010100)

Orphanet (2): GM2 gangliosidosis, AB variant (Orphanet:309246), Tay-Sachs disease (Orphanet:845)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000618	Blindness
HP:0000719	Inappropriate behavior
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001285	Spastic tetraparesis
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0002059	Cerebral atrophy
HP:0002072	Chorea
HP:0002180	Neurodegeneration
HP:0002200	Pseudobulbar signs
HP:0002267	Exaggerated startle response
HP:0002371	Loss of speech
HP:0002376	Developmental regression
HP:0002421	Poor head control
HP:0002476	Primitive reflex
HP:0002478	Progressive spastic quadriplegia
HP:0002835	Aspiration
HP:0003470	Paralysis
HP:0003495	GM2-ganglioside accumulation
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0007256	Abnormal pyramidal sign

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001958_11	Bulimia nervosa	7.000000e-06
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19
GCST006137_8	Serum folate levels	7.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013661	Tay-Sachs Disease	C10.228.140.163.100.435.825.300.300.500; C16.320.565.189.435.825.300.300.500; C16.320.565.398.641.803.350.300.850; C16.320.565.595.554.825.300.300.840; C18.452.132.100.435.825.300.300.500; C18.452.584.563.641.803.350.300.850; C18.452.648.189.435.825.300.300.500; C18.452.648.398.641.803.350.300.850; C18.452.648.595.554.825.300.300.840
D049290	Tay-Sachs Disease, AB Variant	C10.228.140.163.100.435.825.300.300.750; C16.320.565.189.435.825.300.300.750; C16.320.565.398.641.803.350.300.925; C16.320.565.595.554.825.300.300.920; C18.452.132.100.435.825.300.300.750; C18.452.584.563.641.803.350.300.925; C18.452.648.189.435.825.300.300.750; C18.452.648.398.641.803.350.300.925; C18.452.648.595.554.825.300.300.920

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
sodium arsenite	increases expression, affects expression, decreases expression	4
bisphenol A	decreases expression, increases expression, affects expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
dicrotophos	increases expression	1
biochanin A	decreases expression	1
propionaldehyde	increases expression	1
glycidyl methacrylate	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	increases expression, affects cotreatment, decreases expression	1
trichostatin A	increases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	affects cotreatment, increases expression	1
butyraldehyde	increases expression	1
lead chloride	affects cotreatment, increases expression	1
cupric chloride	decreases expression	1
nickel sulfate	decreases expression, increases expression	1
cadmium sulfate	affects cotreatment, increases expression	1
yessotoxin	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D5FG	HeLa::TMEM192-3xHA GM2A partial KO	Cancer cell line	Female
CVCL_U387	GM01675	Finite cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02030015	PHASE4	TERMINATED	Synergistic Enteral Regimen for Treatment of the Gangliosidoses
NCT04221451	PHASE3	TERMINATED	A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
NCT00383448	PHASE2	COMPLETED	HSCT for High Risk Inherited Inborn Errors
NCT03759665	PHASE2	COMPLETED	N-Acetyl-L-Leucine for GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease)
NCT02254863	PHASE1	RECRUITING	UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
NCT04669535	PHASE1	TERMINATED	A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease
NCT00176904	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Inborn Errors of Metabolism
NCT01102686	PHASE1/PHASE2	COMPLETED	Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)
NCT01372228	PHASE1/PHASE2	TERMINATED	Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
NCT00006057	Not specified	COMPLETED	Diagnostic and Screening Study of Genetic Disorders
NCT00668187	Not specified	RECRUITING	A Natural History Study of the Gangliosidoses
NCT01869270	Not specified	COMPLETED	Gene Therapy for Tay-Sachs Disease
NCT01999257	Not specified	COMPLETED	Efficacy Study of an Online Educational Module Before Carrier Genetic Screening in Persons of Ashkenazi Jewish Descent.
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT04470713	Not specified	COMPLETED	Natural History Study for Pediatric Patients With Early Onset of Either GM1 Gangliosidosis, GM2 Gangliosidoses, or Gaucher Disease Type 2
NCT04624789	Not specified	UNKNOWN	Registry Gangliosidoses
NCT05109793	Not specified	COMPLETED	GM1 and GM2 Gangliosidosis PROspective Neurological Disease TrajectOry Study (PRONTO)
NCT06614569	Not specified	ACTIVE_NOT_RECRUITING	Long-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease