IDS

iduronate 2-sulfatase, the group of Sulfatases

Basic information

Region (hg38): X:149476987-149521096

Previous symbols: [ "SIDS" ]

Links

ENSG00000010404 ∙ NCBI:3423 ∙ OMIM:300823 ∙ HGNC:5389 ∙ Uniprot:P22304 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mucopolysaccharidosis type 2 (Definitive), mode of inheritance: XL
• mucopolysaccharidosis type 2 (Definitive), mode of inheritance: XLR
• mucopolysaccharidosis type 2 (Strong), mode of inheritance: AR
• mucopolysaccharidosis type 2 (Strong), mode of inheritance: XL
• mucopolysaccharidosis type 2, severe form (Supportive), mode of inheritance: XL
• mucopolysaccharidosis type 2, attenuated form (Supportive), mode of inheritance: XL
• mucopolysaccharidosis type 2 (Strong), mode of inheritance: XL
• mucopolysaccharidosis type 2 (Definitive), mode of inheritance: XL
• mucopolysaccharidosis type 2 (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mucopolysaccharidosis type II	XL	Biochemical	Enzyme replacement therapy is available and may positively influence biochemical parameters and some outcomes (such as height and endurance), but there is not evidence that the outcome would be positively affected with earlier (genetic) diagnosis, and replacement may not affect neurologic (CNS) manifestations; Awareness of multisystemic involvement, including cardiac manifestations, may allow early and beneficial management of sequelae such as cardiac valvular disease; BMT has been reported	Biochemical; Cardiovascular	4622960; 1901826; 1906048; 1303211; 8111411; 7581397; 8940265; 9660053; 9762601; 9501270; 9921913; 10399096; 16912578; 17185020; 18038146; 19901005; 19748810; 20301451; 21502868; 23497636; 23537841; 25541100; 28595941

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IDS gene.

• Mucopolysaccharidosis, MPS-II (586 variants)
• not provided (97 variants)
• Inborn genetic diseases (71 variants)
• Mucopolysaccharidosis, MPS-III-A (44 variants)
• not specified (20 variants)
• - (3 variants)
• IDS-related condition (2 variants)
• Mucopolysaccharidosis, type II, mild form (2 variants)
• 6 conditions (1 variants)
• Mucopolysaccharidosis type 2, severe form (1 variants)
• Abnormality of lysosomal metabolism (1 variants)
• History of neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IDS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	2	155	17	175
missense	35	56	113	36	13	253
nonsense	32	4	1			37
start loss	1					1
frameshift	42	14				56
inframe indel	2	3	2			7
splice donor/acceptor (+/-2bp)	25	4				29
splice region	2	2	4	20	2	30
non coding		1	2	37	16	56
Total	137	83	120	228	46

Highest pathogenic variant AF is 0.00000897

Variants in IDS

This is a list of pathogenic ClinVar variants found in the IDS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-149482521-TA-T			Benign (Aug 22, 2019)
X-149482521-T-TA			Likely benign (Aug 13, 2019)
X-149482745-C-G		IDS-related disorder	Likely benign (May 18, 2020)
X-149482750-G-C		Mucopolysaccharidosis, MPS-II	Uncertain significance (Jul 02, 2021)
X-149482750-G-T		Mucopolysaccharidosis, MPS-II	Uncertain significance (Mar 13, 2022)
X-149482756-A-T		not specified	Uncertain significance (May 15, 2023)
X-149482757-A-G		Mucopolysaccharidosis, MPS-II • Mucopolysaccharidosis, MPS-III-A	Likely benign (Nov 17, 2023)
X-149482769-G-T		Mucopolysaccharidosis, MPS-II	Uncertain significance (Jul 25, 2023)
X-149482770-A-G		Mucopolysaccharidosis, MPS-II	Likely benign (Apr 17, 2022)
X-149482773-T-G		Mucopolysaccharidosis, MPS-II	Likely benign (Apr 28, 2022)
X-149482776-A-C		Mucopolysaccharidosis, MPS-II	Likely benign (Nov 13, 2023)
X-149482778-C-A		Mucopolysaccharidosis, MPS-II	Uncertain significance (Jun 28, 2023)
X-149482782-G-A		Mucopolysaccharidosis, MPS-II	Likely benign (Apr 13, 2021)
X-149482789-T-C		Mucopolysaccharidosis, MPS-II	Uncertain significance (Jan 11, 2022)
X-149482791-A-G		Mucopolysaccharidosis, MPS-II • IDS-related disorder	Likely benign (Jan 08, 2023)
X-149482801-T-A		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
X-149482808-G-A		Mucopolysaccharidosis, MPS-II	Pathogenic/Likely pathogenic (Nov 16, 2022)
X-149482809-C-CA		Mucopolysaccharidosis, MPS-II	Pathogenic (Jul 24, 2021)
X-149482810-A-T		Mucopolysaccharidosis, MPS-II	Pathogenic (Oct 13, 2021)
X-149482811-A-G		Mucopolysaccharidosis, MPS-II	Likely benign (Jun 01, 2022)
X-149482812-T-C		Mucopolysaccharidosis, MPS-II	Likely benign (Jan 12, 2023)
X-149482815-G-A		Mucopolysaccharidosis, MPS-II	Likely benign (Mar 18, 2023)
X-149482831-T-C		Mucopolysaccharidosis, MPS-II	Likely pathogenic (Sep 07, 2021)
X-149482835-G-A		Mucopolysaccharidosis, MPS-II	Likely benign (Jan 01, 2021)
X-149482836-T-A		Mucopolysaccharidosis, MPS-II	Likely pathogenic (Jan 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IDS	protein_coding	protein_coding	ENST00000340855	9	56950

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00360	125740	0	2	125742	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.58	162	229	0.706	0.0000184	3590
Missense in Polyphen		40	91.673	0.43633		1445
Synonymous	-0.214	100	97.3	1.03	0.00000831	1109
Loss of Function	3.77	0	16.6	0.00	0.00000116	275

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000365	0.0000365
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000122	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the lysosomal degradation of heparan sulfate and dermatan sulfate.
• Disease: DISEASE: Mucopolysaccharidosis 2 (MPS2) [MIM:309900]: An X-linked lysosomal storage disease characterized by intracellular accumulation of heparan sulfate and dermatan sulfate and their excretion in urine. Most children with MPS2 have a severe form with early somatic abnormalities including skeletal deformities, hepatosplenomegaly, and progressive cardiopulmonary deterioration. A prominent feature is neurological damage that presents as developmental delay and hyperactivity but progresses to mental retardation and dementia. They die before 15 years of age, usually as a result of obstructive airway disease or cardiac failure. In contrast, those with a mild form of MPS2 may survive into adulthood, with attenuated somatic complications and often without mental retardation. {ECO:0000269|PubMed:10215411, ECO:0000269|PubMed:10220152, ECO:0000269|PubMed:10447264, ECO:0000269|PubMed:10671065, ECO:0000269|PubMed:10838181, ECO:0000269|PubMed:11015461, ECO:0000269|PubMed:11683780, ECO:0000269|PubMed:11731225, ECO:0000269|PubMed:12655569, ECO:0000269|PubMed:12794697, ECO:0000269|PubMed:1284597, ECO:0000269|PubMed:1303211, ECO:0000269|PubMed:16699754, ECO:0000269|PubMed:7581397, ECO:0000269|PubMed:7599640, ECO:0000269|PubMed:7728156, ECO:0000269|PubMed:7866405, ECO:0000269|PubMed:7887413, ECO:0000269|PubMed:7981716, ECO:0000269|PubMed:8281149, ECO:0000269|PubMed:8566953, ECO:0000269|PubMed:8664909, ECO:0000269|PubMed:8830188, ECO:0000269|PubMed:8940265, ECO:0000269|PubMed:9222763, ECO:0000269|PubMed:9266380, ECO:0000269|PubMed:9375851, ECO:0000269|PubMed:9452044, ECO:0000269|PubMed:9501270, ECO:0000269|PubMed:9660053, ECO:0000269|PubMed:9762601, ECO:0000269|PubMed:9875019, ECO:0000269|PubMed:9921913, ECO:0000269|PubMed:9950361}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Glycosaminoglycan degradation - Homo sapiens (human);Metabolism of carbohydrates;HS-GAG degradation;Heparan sulfate/heparin (HS-GAG) metabolism;CS/DS degradation;Chondroitin sulfate/dermatan sulfate metabolism;Glycosaminoglycan metabolism;Metabolism (Consensus)

Recessive Scores

• pRec: 0.254

Intolerance Scores

• rvis_EVS: 0.38
• rvis_percentile_EVS: 75.51

Haploinsufficiency Scores

• pHI: 0.216
• hipred: Y
• hipred_score: 0.534
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0204

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ids
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype

Zebrafish Information Network

• Gene name: ids
• Affected structure: atrioventricular valve
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: glycosaminoglycan catabolic process;chondroitin sulfate catabolic process
• Cellular component: lysosomal lumen
• Molecular function: iduronate-2-sulfatase activity;sulfuric ester hydrolase activity;metal ion binding