IDS

Chr XXLR

iduronate 2-sulfatase

Also known as: ID2S, MPS2, SIDS

NCBI Gene: 3423 ENSG00000010404 UniProt: P22304 OMIM: 300823

The protein functions as a lysosomal enzyme that degrades heparan sulfate and dermatan sulfate through its sulfatase activity. Mutations cause mucopolysaccharidosis type II (Hunter syndrome), an X-linked recessive lysosomal storage disorder. Loss of enzyme function leads to accumulation of these glycosaminoglycans in lysosomes, resulting in the progressive multisystem manifestations characteristic of Hunter syndrome.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Mucopolysaccharidosis IIMIM #309900

XLR

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mucopolysaccharidosis type 2 · XL · ClinGen 2018

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

1127

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — IDS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.18LOEUF

pLI 0.996

Z-score 3.77

OE 0.00 (0.00–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.58Z-score

OE missense 0.71 (0.62–0.81)

162 obs / 229.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.18)

0≤0.351.4

Missense OE?0.71 (0.62–0.81)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 0 / 16.6Missense obs/exp: 162 / 229.3Syn Z: -0.21

Background carrier burden — how many people carry a rare variant somewhere in IDS?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

399 rare PASS variants

Rare truncating (LoF)

1 in 10,000

13 rare PASS variants

Rare synonymous (reference)

1 in 130

222 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IDS. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 190	1 in 7,000
South Asian	~36k	1 in 110	none seen
Remaining (unassigned)	~31k	1 in 120	1 in 980
European (Finnish)	~27k	1 in 200	none seen
Admixed American	~23k	1 in 120	≈ 1 in 23,000
African / African American	~21k	1 in 130	none seen
East Asian	~20k	1 in 110	none seen
Ashkenazi Jewish	~13k	1 in 980	none seen
Middle Eastern	~2,758	1 in 98	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 9 coding exons well covered in gnomAD exomes and genomes.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

IDS · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — IDS

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Mucopolysaccharidosis II

Gene Therapy With Modified Autologous Hematopoietic Stem Cells for Patients With Mucopolysaccharidosis Type II

ACTIVE NOT RECRUITING

NCT05665166Phase PHASE1, PHASE2University of ManchesterStarted 2023-06-01

Autologous CD34+ HSCs transduced ex vivo with CD11B LV encoding human IDS tagged with ApoEII

Mucopolysaccharidosis II

Long-term Follow-Up for RGX-121

ACTIVE NOT RECRUITING

NCT04597385REGENXBIO Inc.Started 2021-03-14

Long-term Follow-Up

Mucopolysaccharidosis II

An Extension Study of the Long-Term Safety, Tolerability, and Efficacy of Tividenofusp Alfa (DNL310) in Participants With Mucopolysaccharidosis Type II (MPS II) From Study DNLI-E-0002 or Study DNLI-E-0007

ENROLLING BY INVITATION

NCT06075537Phase PHASE2, PHASE3Denali Therapeutics Inc.Started 2023-09-20

tividenofusp alfa

MPS IIHunter Syndrome (MPS II)

RGX-121-3102 Gene Therapy in Participants With MPS II (Hunter Syndrome)

ACTIVE NOT RECRUITING

NCT07236606Phase PHASE3REGENXBIO Inc.Started 2025-11-25

RGX-121-3102

Mucopolysaccharidosis Type II (MPS II)

CAMPSIITE™ RGX-121 Gene Therapy in Subjects With MPS II (Hunter Syndrome)

ACTIVE NOT RECRUITING

NCT03566043Phase PHASE2, PHASE3REGENXBIO Inc.Started 2018-09-27