Tay-Sachs disease, B1 variant

Summary

Tay-Sachs disease, B1 variant (MONDO:0017728) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Tay-Sachs disease, B1 variant
Mondo ID	MONDO:0017728
Orphanet	309239
SNOMED CT	238024005
UMLS	C1848916
MedGen	336452
GARD	0021327
Is cancer (heuristic)	no

Also known as: GM2 gangliosidosis, B1 variant · hexosaminidase A deficiency, B1 variant

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › Tay-Sachs disease › Tay-Sachs disease, B1 variant

Related subtypes (3): Tay-Sachs disease, b variant, infantile form, Tay-Sachs disease, b variant, juvenile form, Tay-Sachs disease, B variant, adult form

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
446267	NM_000520.4(HEXA):c.[574G>C;598G>A]		Pathogenic	no assertion criteria provided
3896	NM_000520.6(HEXA):c.533G>A (p.Arg178His)	HEXA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3897	NM_000520.6(HEXA):c.532C>T (p.Arg178Cys)	HEXA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3921	NM_000520.6(HEXA):c.959GAG[1] (p.Gly321del)	HEXA	Pathogenic	no assertion criteria provided
3924	NM_000520.6(HEXA):c.772G>C (p.Asp258His)	HEXA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HEXA	Orphanet:309178	Tay-Sachs disease, infantile form
HEXA	Orphanet:309185	Tay-Sachs disease, juvenile form
HEXA	Orphanet:309192	Tay-Sachs disease, adult form

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HEXA	HGNC:4878	ENSG00000213614	P06865	Beta-hexosaminidase subunit alpha	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HEXA	Beta-hexosaminidase subunit alpha	Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HEXA	Enzyme (other)	yes	3.2.1.169	GH20_cat, GH_hydrolase_sf, GH20

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gall bladder	1
stromal cell of endometrium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HEXA	293	ubiquitous	marker	type B pancreatic cell, gall bladder, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HEXA	999

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HEXA	P06865	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective HEXA causes GM2G1 (Hyaluronan metabolism)	1	11420.0×	4e-04	HEXA
Keratan sulfate degradation	1	713.8×	0.002	HEXA
Hyaluronan degradation	1	713.8×	0.002	HEXA
CS/DS degradation	1	543.8×	0.002	HEXA
Glycosphingolipid catabolism	1	292.8×	0.003	HEXA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
dermatan sulfate proteoglycan catabolic process	1	4213.0×	0.003	HEXA
glycosaminoglycan metabolic process	1	2407.4×	0.003	HEXA
ganglioside catabolic process	1	1872.4×	0.003	HEXA
cell morphogenesis involved in neuron differentiation	1	1532.0×	0.003	HEXA
neuromuscular process controlling posture	1	1053.2×	0.003	HEXA
hyaluronan catabolic process	1	991.3×	0.003	HEXA
glycosaminoglycan biosynthetic process	1	842.6×	0.003	HEXA
N-glycan processing	1	732.7×	0.003	HEXA
lipid storage	1	543.6×	0.003	HEXA
adult walking behavior	1	495.6×	0.003	HEXA
neuromuscular process controlling balance	1	330.4×	0.004	HEXA
lysosome organization	1	306.4×	0.004	HEXA
myelination	1	251.5×	0.005	HEXA
carbohydrate metabolic process	1	135.9×	0.008	HEXA
skeletal system development	1	125.8×	0.008	HEXA
sensory perception of sound	1	100.9×	0.010	HEXA

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HEXA	PYRIMETHAMINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HEXA	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRIMETHAMINE	4	HEXA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HEXA	58	Binding:58

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HEXA	3.2.1.169	protein O-GlcNAcase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PYRIMETHAMINE	4	HEXA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HEXA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.