SGSH

Chr 17

N-sulfoglucosamine sulfohydrolase

Also known as: HSS, MPS3A, SFMD

NCBI Gene: 6448 ENSG00000181523 UniProt: P51688

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.80

Clinical Summary— SGSH

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Gene-Disease Validity (ClinGen)

mucopolysaccharidosis type 3A · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

218 unique Pathogenic / Likely Pathogenic· 620 VUS of 1704 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SGSH

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.24

OE 0.47 (0.29–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.05Z-score

OE missense 1.01 (0.92–1.10)

336 obs / 333.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.47 (0.29–0.80)

0≤0.351.4

Missense OE?1.01 (0.92–1.10)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 10 / 21.1Missense obs/exp: 336 / 333.2Syn Z: -0.91

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSGSH-related mucopolysaccharidosisLOFAR

This gene — mechanism propensity

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

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

1704 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68

Likely Pathogenic150

VUS620

Likely Benign673

Benign76

Conflicting92

Pathogenic

150

Likely Pathogenic

620

VUS

673

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	48	12	8	0	68
Likely Pathogenic	85	64	1	0	150
VUS	32	520	56	12	620
Likely Benign	0	19	238	416	673
Benign	0	6	58	12	76
Conflicting	—				92
Total	165	621	361	440	1,679

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

16 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap SGSH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →