SULF1

Chr 8

sulfatase 1

Also known as: SULF-1

NCBI Gene: 23213ENSG00000137573UniProt: Q8IWU6

The protein functions as an extracellular heparan sulfate endosulfatase that selectively removes 6-O-sulfate groups from heparan sulfate proteoglycans, regulating heparin-dependent growth factor signaling. Mutations cause autosomal recessive brachyolmia type 3, a skeletal dysplasia characterized by short stature and distinctive spinal abnormalities. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
26
Pubs (1 yr)
29
P/LP submissions
0%
P/LP missense
0.46
LOEUF
DN
Mechanism· predicted
Clinical Summary— SULF1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 225 VUS of 421 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.001
Z-score 4.59
OE 0.30 (0.20–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.51Z-score
OE missense 0.81 (0.75–0.88)
414 obs / 509.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.20–0.46)
0≤0.351.4
Missense OE0.81 (0.75–0.88)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 15 / 50.1Missense obs/exp: 414 / 509.7Syn Z: -0.43
DN
0.75top 25%
GOF
0.4678th %ile
LOF
0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

421 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
VUS225
Likely Benign105
Benign24
Conflicting2
29
Pathogenic
225
VUS
105
Likely Benign
24
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
0
0
0
VUS
5
198
21
1
225
Likely Benign
0
10
35
60
105
Benign
1
3
14
6
24
Conflicting
—2
Total62119967385

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SULF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Investigating the anti-cancer potential of sulfatase 1 and its underlying mechanism in non-small cell lung cancer
Zhang B et al.·Cytojournal
2024Functional
Differential Expression of COL1A1, COL1A2, COL6A3, and SULF1 as Prognostic Biomarkers in Gastric Cancer
Hu Y et al.·Int J Gen Med
2021
Validation of Novel Molecular Imaging Targets Identified by Functional Genomic mRNA Profiling to Detect Dysplasia in Barrett's Esophagus
Zhao X et al.·Cancers (Basel)
2022Functional
Extracellular Heparan 6-O-Endosulfatases SULF1 and SULF2 in Head and Neck Squamous Cell Carcinoma and Other Malignancies
Yang Y et al.·Cancers (Basel)
2022
Overexpression of DDIT4 and TPTEP1 are associated with metastasis and advanced stages in colorectal cancer patients: a study utilizing bioinformatics prediction and experimental validation
Fattahi F et al.·Cancer Cell Int
2021Cohort
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Altered Excitability and Glutamatergic Synaptic Transmission in the Medium Spiny Neurons of the Nucleus Accumbens in Mice Deficient in the Heparan Sulfate Endosulfatase Sulf1.
Miya K et al.·eNeuro
2026Open Access
SULF1 in Cancer Associated Fibroblasts Promotes Invasion in Head and Neck Cancer Cell Lines.
Mukherjee P et al.·Cancer Med
2026Open Access
Essential Roles of Heparan Sulfate Endosulfatase Sulf1 in Reward and Aversion Learning Through Distinct Dopamine D1 and D2 Receptor Pathways in Male Mice.
Miya K et al.·J Neurochem
2026Open Access
MARCHF1-mediated SULF1 degradation blocks THBS2/TGF-β/SMAD2/3 signaling to reverse colon cancer metastasis and 5-FU resistance.
Li H et al.·iScience
2026Open Access
SULF1's Role in Endothelial Senescence and Atherosclerosis: Insights from Single-Cell and Bulk Transcriptomics.
Jiang MT et al.·J Inflamm Res
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients