NDST1

N-deacetylase and N-sulfotransferase 1, the group of Sulfotransferases, membrane bound

Basic information

Region (hg38): 5:150485817-150558211

Previous symbols: [ "HSST" ]

Links

ENSG00000070614 ∙ NCBI:3340 ∙ OMIM:600853 ∙ HGNC:7680 ∙ Uniprot:P52848 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 46 (Strong), mode of inheritance: AR
• intellectual disability, autosomal recessive 46 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 46	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	21937992; 25125150

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDST1 gene.

• not provided (112 variants)
• Inborn genetic diseases (36 variants)
• not specified (31 variants)
• Intellectual disability, autosomal recessive 46 (23 variants)
• Intellectual disability (4 variants)
• Global developmental delay (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDST1 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	46	13	60
missense		2	70	5		77
nonsense			2			2
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			3	6		9
non coding			1	6	6	13
Total	0	2	75	57	19

Variants in NDST1

This is a list of pathogenic ClinVar variants found in the NDST1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-150521240-G-T			Benign (Jun 05, 2021)
5-150521252-A-C		NDST1-related disorder	Likely benign (Aug 03, 2023)
5-150521277-G-A			Uncertain significance (Apr 25, 2022)
5-150521281-G-C		Inborn genetic diseases	Uncertain significance (Oct 25, 2022)
5-150521293-C-G		Intellectual disability, autosomal recessive 46	Uncertain significance (Aug 14, 2019)
5-150521294-G-A		Intellectual disability	Likely benign (Jan 01, 2019)
5-150521301-C-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
5-150521302-G-A			Likely benign (Jul 23, 2022)
5-150521327-A-G		not specified	Likely benign (Jul 14, 2023)
5-150521355-C-G		not specified	Uncertain significance (May 01, 2017)
5-150521396-T-C		Inborn genetic diseases	Uncertain significance (Jun 14, 2023)
5-150521397-C-G		not specified	Uncertain significance (Nov 25, 2015)
5-150521398-G-A		not specified • NDST1-related disorder	Likely benign (Jul 12, 2019)
5-150521410-C-T			Likely benign (Feb 09, 2022)
5-150521415-C-G			Uncertain significance (Nov 24, 2021)
5-150521422-C-T			Likely benign (Dec 31, 2019)
5-150521423-G-A		not specified	Uncertain significance (Apr 08, 2022)
5-150521430-C-G		Intellectual disability	Uncertain significance (Feb 04, 2020)
5-150521433-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
5-150521442-C-T			Uncertain significance (Apr 04, 2019)
5-150521451-G-A			Uncertain significance (Oct 05, 2022)
5-150521467-G-A			Benign (Mar 18, 2023)
5-150521481-C-T			Uncertain significance (Apr 25, 2022)
5-150521493-G-A		not specified • Inborn genetic diseases • Intellectual disability, autosomal recessive 46 • Intellectual disability • NDST1-related disorder	Conflicting classifications of pathogenicity (Oct 29, 2023)
5-150521502-C-T		Inborn genetic diseases	Uncertain significance (Feb 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDST1	protein_coding	protein_coding	ENST00000261797	14	72393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000451	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.92	353	545	0.648	0.0000377	5778
Missense in Polyphen		109	223.52	0.48765		2347
Synonymous	-0.126	247	245	1.01	0.0000183	1771
Loss of Function	5.54	3	41.5	0.0722	0.00000237	435

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000867	0.0000867
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000373	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential bifunctional enzyme that catalyzes both the N- deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis (PubMed:10758005, PubMed:12634318). Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Compared to other NDST enzymes, its presence is absolutely required. Participates in biosynthesis of heparan sulfate that can ultimately serve as L-selectin ligands, thereby playing a role in inflammatory response (PubMed:10758005, PubMed:12634318). Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:10758005, ECO:0000269|PubMed:12634318, ECO:0000269|PubMed:22660413}.
• Pathway: Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human);Metapathway biotransformation Phase I and II;Metabolism of carbohydrates;HS-GAG biosynthesis;Heparan sulfate/heparin (HS-GAG) metabolism;Glycosaminoglycan metabolism;heparan sulfate biosynthesis (late stages);heparan sulfate biosynthesis;Metabolism (Consensus)

Recessive Scores

• pRec: 0.185

Intolerance Scores

• loftool: 0.0415
• rvis_EVS: -1.75
• rvis_percentile_EVS: 2.36

Haploinsufficiency Scores

• pHI: 0.756
• hipred: Y
• hipred_score: 0.685
• ghis: 0.564

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.500

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ndst1
• Phenotype: endocrine/exocrine gland phenotype; taste/olfaction phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype; hearing/vestibular/ear 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); digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: ndst1a
• Affected structure: basihyal cartilage
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: glycosaminoglycan biosynthetic process;protein sulfation;inflammatory response;heparan sulfate proteoglycan biosynthetic process;heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process;heparin biosynthetic process
• Cellular component: Golgi membrane;Golgi apparatus;integral component of membrane
• Molecular function: protein binding;[heparan sulfate]-glucosamine N-sulfotransferase activity;deacetylase activity;heparan sulfate sulfotransferase activity;heparan sulfate N-acetylglucosaminyltransferase activity;N-acetylglucosamine deacetylase activity