HEXB

Chr 5AR

hexosaminidase subunit beta

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

Hexosaminidase B encodes the beta subunit of lysosomal beta-hexosaminidase, which degrades GM2 ganglioside and other molecules containing terminal N-acetyl hexosamines. Mutations cause Sandhoff disease (GM2-gangliosidosis type II) with infantile, juvenile, and adult forms through autosomal recessive inheritance. The pathogenic mechanism involves accumulation of GM2 ganglioside in neurons leading to neurodegeneration.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.921 OMIM phenotype
Clinical SummaryHEXB
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Gene-Disease Validity (ClinGen)
Sandhoff disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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 OE0.63 (0.440.92)
00.351.4
Missense OE0.89 (0.810.99)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 20 / 31.7Missense obs/exp: 260 / 291.1Syn Z: -0.26
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHEXB-related GM2-gangliosidosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7131th %ile
GOF
0.6444th %ile
LOF
0.2191th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

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.

3D Protein StructureAlphaFold
Clinical Literature
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