IDS

Chr XXLR

iduronate 2-sulfatase

NCBI Gene: 3423ENSG00000010404UniProt: P22304

Lysosomal enzyme involved in the degradation pathway of dermatan sulfate and heparan sulfate

Primary Disease Associations & Inheritance

Mucopolysaccharidosis IIMIM #309900
XLR
446
ClinVar variants
250
Pathogenic / LP
1.00
pLI score· haploinsufficient
12
Active trials
Clinical Summary— IDS
🧬
Gene-Disease Validity (ClinGen)
mucopolysaccharidosis type 2 · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
250 Pathogenic / Likely Pathogenic· 108 VUS of 446 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.58Z-score
OE missense 0.71 (0.62–0.81)
162 obs / 229.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.62–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 0 / 16.6Missense obs/exp: 162 / 229.3Syn Z: -0.21

ClinVar Variant Classifications

446 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic159
Likely Pathogenic91
VUS108
Likely Benign78
Benign3
Conflicting7
159
Pathogenic
91
Likely Pathogenic
108
VUS
78
Likely Benign
3
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
93
25
41
0
159
Likely Pathogenic
22
57
11
1
91
VUS
3
91
12
2
108
Likely Benign
0
7
34
37
78
Benign
0
0
3
0
3
Conflicting
—7
Total11818010140446

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

View in 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.

Gene2Phenotype Curations

IDS-related mucopolysaccharidosis

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mucopolysaccharidosis II

MIM #309900

Molecular basis of disorder known

X-linked recessive
📖
GeneReview available — IDS
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Immediate dentin sealing: a fundamental procedure for indirect bonded restorations.
Magne P·J Esthet Restor Dent
2005Review
A Blood-Brain-Barrier-Penetrating Anti-human Transferrin Receptor Antibody Fusion Protein for Neuronopathic Mucopolysaccharidosis II.
Sonoda H et al.·Mol Ther
2018
Significance of immediate dentin sealing and flowable resin coating reinforcement for unfilled/lightly filled adhesive systems.
de Carvalho MA et al.·J Esthet Restor Dent
2021
Molecular basis of mucopolysaccharidosis type II (Hunter syndrome): first review and classification of published IDS gene variants.
Zanetti A et al.·Hum Genomics
2024Review
The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression.
Rush AJ et al.·Biol Psychiatry
2003Clinical trial
Comparison of survival between primary debulking surgery and neoadjuvant chemotherapy for stage III/IV ovarian, tubal and peritoneal cancers in phase III randomised trial.
Onda T et al.·Eur J Cancer
2020Clinical trial
The diagnosis and management of mucopolysaccharidosis type II.
Mao SJ et al.·Ital J Pediatr
2024Review
Comprehensive molecular and clinical findings in 29 patients with multi-locus imprinting disturbance.
Urakawa T et al.·Clin Epigenetics
2024Cohort
Genotype-phenotype findings in patients with mucopolysaccharidosis II from the Hunter Outcome Survey.
Muenzer J et al.·Mol Genet Metab
2024Cohort
Immunodeficiency mutation databases (IDbases).
Piirilä H et al.·Hum Mutat
2006Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Fallopian Tube Endometrioid AdenocarcinomaFallopian Tube High Grade Serous AdenocarcinomaOvarian Endometrioid Adenocarcinoma

Testing the Addition of Ipatasertib to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) for Stage III or IV Epithelial Ovarian Cancer

ACTIVE NOT RECRUITING
NCT05276973Phase PHASE1National Cancer Institute (NCI)Started 2022-09-08
BiopsyCarboplatinIpatasertib
Chronic Rhinosinusitis (Diagnosis)

Topical Probiotic Sinus Irrigations for Treating Chronic Sinusitis

RECRUITING
NCT05427695Phase PHASE2University of Illinois at ChicagoStarted 2025-02-05
Lactobacillus sakei proBio65Isotonic Saline Solution
Carcinoma, Pancreatic DuctalColorectal NeoplasmsCarcinoma, Non-Small-Cell Lung

A Study to Learn About the Study Medicine PF-07985045 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Change in a Gene.

ACTIVE NOT RECRUITING
NCT06704724Phase PHASE1PfizerStarted 2024-12-10
PF-07985045GemcitabineNab-paclitaxel
Mucopolysaccharidosis II

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

RECRUITING
NCT05665166Phase PHASE1, PHASE2University of ManchesterStarted 2023-06-01
Autologous CD34+ HSCs transduced ex vivo with CD11B LV encoding human IDS tagged with ApoEII
Hemophilia A

Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults

ACTIVE NOT RECRUITING
NCT04370054Phase PHASE3PfizerStarted 2020-08-18
PF-07055480 (giroctocogene fitelparovec): Recombinant AAV2/6 Human Factor VIII Gene Therapy
Hemophilia BMucopolysaccharidosis IMucopolysaccharidosis II

Long Term Follow-up (LTFU) of Subjects Who Received SB-318, SB-913, or SB-FIX

ACTIVE NOT RECRUITING
NCT04628871Sangamo TherapeuticsStarted 2020-11-03
SB-318SB-913SB-FIX
Carcinoma, Pancreatic DuctalColorectal NeoplasmsCarcinoma, Non-Small-Cell Lung

A Study to Learn About the Study Medicine PF-07934040 When Given Alone or With Other Anti-cancer Therapies in People With Advanced Solid Tumors That Have a Genetic Mutation.

RECRUITING
NCT06447662Phase PHASE1PfizerStarted 2024-06-27
PF-07934040GemcitabineNab-paclitaxel
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
RGX-121
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet
Pancreatic CancerPancreatic Ductal AdenocarcinomaPDAC

A Prospective Registry for Patients at High-Risk for Pancreatic Cancer

RECRUITING
NCT06151223Mayo ClinicStarted 2021-07-13
Bio-specimen Collection: BloodBio-specimen Collection: Pancreatic JuiceMRI
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
Ovarian CancerFallopian Tube CancerPeritoneal Cancer

Microdevice In Ovarian, Fallopian Tube, And Peritoneal Cancer

RECRUITING
NCT04701645Phase PHASE1Brigham and Women's HospitalStarted 2022-11-01
Microdevice

External Resources

Links to major genomics databases and tools