SULF1

protein-coding

sulfatase 1, the group of Sulfatases

Gene summary

This gene encodes an extracellular heparan sulfate endosulfatase. The encoded enzyme selectively removes 6-O-sulfate groups from heparan sulfate chains of heparan sulfate proteoglycans (HSPGs). The enzyme is secreted through the Golgi and is subsequently localized to the cell surface. The expression of this gene may be down-regulated in several types of cancer, including hepatocellular (HCC), ovarian and breast cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

MANE transcript

NM_001128205.2

Inheritance

—

ClinVar variants

U:275B:112

Top phenotype

SULF1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr8:69,466,624-69,660,915

External References & Databases

Ensembl (ENSG00000137573)

Transcript & Mutation Effects

hg38 • Region Span ~194.3 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 SULF1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 364

not specifiedTotal: 125

SULF1-related disorderTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 2

Anophthalmia-microphthalmia syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001128205.2. 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	91 clinvar	8 clinvar	103
missense			247 clinvar	9 clinvar	4 clinvar	260
nonsense			8 clinvar			8
start loss						0
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	275	100	12	387

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001128205.2	RefSeq	NP_001121677.1	19	MANE Select
ENST00000402687.9	Ensembl	ENSP00000385704.4	19	MANE Select
NM_001128204.2	RefSeq	NP_001121676.1	19	Standard
NM_001128206.2	RefSeq	NP_001121678.1	19	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sulf1	Danio rerio	Structure: muscle cell Quality: sparse abnormal

Gene / Model

Organism

Observed Phenotype

sulf1

Danio rerio

Structure: muscle cell

Quality: sparse

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

kidney development
negative regulation of endothelial cell proliferation
chondrocyte development
glomerular filtration
apoptotic process

Molecular Function

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

Cellular Component

extracellular space
endoplasmic reticulum
Golgi apparatus
Golgi stack
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260128
Coding exons: 19
Length: 194292
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	414	510	0.812	0.0000293	5794
Missense (PolyPhen)		109	169.93	0.64143		1864
Synonymous	-0.430	195	188	1.04	0.0000112	1562
Loss of Function	4.59	15	50.1	0.300	0.00000280	575

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00011	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00027	0.00026	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. Diminishes HSPG (heparan sulfate proteoglycans) sulfation, inhibits signaling by heparin-dependent growth factors, diminishes proliferation, and facilitates apoptosis in response to exogenous stimulation.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.0170
RVIS EVS: -0.48
RVIS percentile EVS: 22.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0324

Gene Damage Prediction

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