SULF2

protein-coding

sulfatase 2, the group of Sulfatases

Gene summary

Heparan sulfate proteoglycans (HSPGs) act as coreceptors for numerous heparin-binding growth factors and cytokines and are involved in cell signaling. Heparan sulfate 6-O-endosulfatases, such as SULF2, selectively remove 6-O-sulfate groups from heparan sulfate. This activity modulates the effects of heparan sulfate by altering binding sites for signaling molecules (Dai et al., 2005 [PubMed 16192265]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001387048.1

Inheritance

—

ClinVar variants

U:150B:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr20:47,656,197-47,786,616

External References & Databases

Ensembl (ENSG00000196562)

Transcript & Mutation Effects

hg38 • Region Span ~130.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SULF2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 138

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001387048.1. 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			4 clinvar	6 clinvar	2 clinvar	12
missense			139 clinvar	8 clinvar	1 clinvar	148
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	150	14	3	167

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001387048.1	RefSeq	NP_001373977.1	20	MANE Select
ENST00000688720.1	Ensembl	ENSP00000508753.1	20	MANE Select
NM_001161841.2	RefSeq	NP_001155313.1	20	Standard
NM_001387049.1	RefSeq	NP_001373978.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

kidney development
chondrocyte development
glomerular filtration
response to wounding
positive regulation of vascular endothelial growth factor production

Molecular Function

arylsulfatase activity
calcium ion binding
glycosaminoglycan binding
N-acetylglucosamine-6-sulfatase activity

Cellular Component

extracellular space
endoplasmic reticulum
Golgi stack
plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359930
Coding exons: 20
Length: 130269
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.72	442	556	0.795	0.0000368	5733
Missense (PolyPhen)		169	255.19	0.66225		2624
Synonymous	0.255	225	230	0.979	0.0000166	1593
Loss of Function	4.57	13	46.7	0.278	0.00000240	533

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Exhibits arylsulfatase activity and highly specific endoglucosamine-6-sulfatase activity. It can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin.;

Intolerance Scores

LoFtool: 0.0167
RVIS EVS: -1.59
RVIS percentile EVS: 3.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.665

Gene Damage Prediction

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