NDST2

protein-coding

N-deacetylase and N-sulfotransferase 2, the group of Sulfotransferases, membrane bound

Gene summary

This gene encodes a member of the N-deacetylase/N-sulfotransferase subfamily of the sulfotransferase 1 proteins. The encoded enzyme has dual functions in processing glucosamine and heparin polymers, including N-deacetylation and N-sulfation. The encoded protein may be localized to the Golgi. [provided by RefSeq, Feb 2009]

MANE transcript

NM_003635.4

Inheritance

—

ClinVar variants

U:149B:4

Top phenotype

Anophthalmia-microphthalmia syndrome

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr10:73,801,911-73,811,798

External References & Databases

Ensembl (ENSG00000166507)

Transcript & Mutation Effects

hg38 • Region Span ~9.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NDST2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 141

not providedTotal: 3

Anophthalmia-microphthalmia syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003635.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			142 clinvar	4 clinvar		146
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	149	4	0	153

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003635.4	RefSeq	NP_003626.1	13	MANE Select
ENST00000309979.11	Ensembl	ENSP00000310657.6	13	MANE Select
NM_001330107.2	RefSeq	NP_001317036.1	12	Standard
ENST00000299641.8	Ensembl	ENSP00000299641.5	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

glycosaminoglycan biosynthetic process
heparan sulfate proteoglycan biosynthetic process
heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process
heparin biosynthetic process

Molecular Function

[heparan sulfate]-glucosamine N-sulfotransferase activity
deacetylase activity
heparan sulfate sulfotransferase activity
heparan sulfate N-acetylglucosaminyltransferase activity
N-acetylglucosamine deacetylase activity

Cellular Component

Golgi membrane
Golgi apparatus
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309979
Coding exons: 13
Length: 9921
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125748
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.55	437	539	0.811	0.0000342	5732
Missense (PolyPhen)		159	237.93	0.66825		2684
Synonymous	0.311	195	201	0.972	0.0000106	1853
Loss of Function	4.44	10	40.5	0.247	0.00000234	412

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.00023	0.00018	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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. Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:10758005, ECO:0000269|PubMed:12634318, ECO:0000269|PubMed:16343444, ECO:0000269|PubMed:22660413}.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.360
RVIS EVS: -1.7
RVIS percentile EVS: 2.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.195

Gene Damage Prediction

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