SUMF1

Chr 3AR

sulfatase modifying factor 1

Also known as: AAPA3037, FGE, UNQ3037

NCBI Gene: 285362ENSG00000144455UniProt: Q8NBK3

This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Multiple sulfatase deficiencyMIM #272200
AR
532
ClinVar variants
119
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SUMF1
🧬
Gene-Disease Validity (ClinGen)
mucosulfatidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
119 Pathogenic / Likely Pathogenic· 162 VUS of 532 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.07LOEUF
pLI 0.000
Z-score 1.31
OE 0.69 (0.46–1.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.50Z-score
OE missense 1.10 (0.98–1.22)
236 obs / 215.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.46–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (0.98–1.22)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 15 / 21.6Missense obs/exp: 236 / 215.4Syn Z: -0.76

ClinVar Variant Classifications

532 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic82
Likely Pathogenic37
VUS162
Likely Benign241
Benign8
Conflicting2
82
Pathogenic
37
Likely Pathogenic
162
VUS
241
Likely Benign
8
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
4
58
0
82
Likely Pathogenic
13
17
7
0
37
VUS
1
126
30
5
162
Likely Benign
0
3
106
132
241
Benign
0
1
5
2
8
Conflicting
—2
Total34151206139532

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

View in ClinVar →

Protein Context — Lollipop Plot

SUMF1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SUMF1-related multiple sulfatase deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Multiple sulfatase deficiency

MIM #272200

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SUMF1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson's disease.
Rutledge J et al.·Acta Neuropathol
2024
New mouse models with hypomorphic SUMF1 variants mimic attenuated forms of multiple sulfatase deficiency.
Sorrentino NC et al.·J Inherit Metab Dis
2023Functional
A homozygous missense variant of SUMF1 in the Bedouin population extends the clinical spectrum in ultrarare neonatal multiple sulfatase deficiency.
Staretz-Chacham O et al.·Mol Genet Genomic Med
2020Case report
Late infantile form of multiple sulfatase deficiency with a novel missense variant in the SUMF1 gene: case report and review.
Sheth J et al.·BMC Pediatr
2023Case report
Hematopoietic stem cell gene therapy improves outcomes in a clinically relevant mouse model of multiple sulfatase deficiency.
Pham V et al.·Mol Ther
2024Functional
Novel drug targets for delirium based on genetic causality.
Zhu S et al.·J Affect Disord
2025
Sulfatase modifying factor 1 (SUMF1) is associated with Chronic Obstructive Pulmonary Disease.
Weidner J et al.·Respir Res
2017
SUMF1 Common Variant rs793391 Is Associated with Response to Inhaled Corticosteroids in Patients with COPD.
Ntenti C et al.·Int J Mol Sci
2025Cohort
Non-syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity.
Lin S et al.·Clin Genet
2024Case report
Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.
Roberts JL et al.·Gene
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools