SGSH

Chr 17AR

N-sulfoglucosamine sulfohydrolase

Also known as: HSS, MPS3A, SFMD

The protein encodes sulfamidase, a lysosomal enzyme that degrades heparan sulfate. Mutations cause mucopolysaccharidosis type IIIA (Sanfilippo syndrome A), an autosomal recessive lysosomal storage disorder characterized by impaired heparan sulfate degradation leading to progressive neurodegeneration. Loss of enzyme function results in toxic accumulation of heparan sulfate within lysosomes.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.801 OMIM phenotype
Clinical SummarySGSH
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Gene-Disease Validity (ClinGen)
mucopolysaccharidosis type 3A · 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
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — SGSH
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
0.80LOEUF
pLI 0.000
Z-score 2.24
OE 0.47 (0.290.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.05Z-score
OE missense 1.01 (0.921.10)
336 obs / 333.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.47 (0.290.80)
00.351.4
Missense OE1.01 (0.921.10)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 10 / 21.1Missense obs/exp: 336 / 333.2Syn Z: -0.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSGSH-related mucopolysaccharidosisLOFAR

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

DN
0.7130th %ile
GOF
0.6346th %ile
LOF
0.2386th %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

SGSH · 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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