HEXB

Chr 5AR

hexosaminidase subunit beta

Also known as: ENC-1AS, HEL-248, HEL-S-111

Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Sandhoff disease, infantile, juvenile, and adult formsMIM #268800
AR
UniProtGM2-gangliosidosis 2

Clinical highlights

Gene-disease validity (ClinGen)
Sandhoff disease · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
55
Pubs (1 yr)
P/LP submissions
P/LP missense
0.92
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — HEXB
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.92LOEUF
pLI 0.000
Z-score 1.93
OE 0.63 (0.440.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.65Z-score
OE missense 0.89 (0.810.99)
260 obs / 291.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.63 (0.440.92)
00.351.4
Missense OE?0.89 (0.810.99)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 20 / 31.7Missense obs/exp: 260 / 291.1Syn Z: -0.26

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HEXB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.