SUMF1

Chr 3AR

sulfatase modifying factor 1

Also known as: AAPA3037, FGE, UNQ3037

This gene encodes formylglycine-generating enzyme, which activates sulfatases by oxidizing a cysteine residue to form the essential 3-oxoalanine (formylglycine) residue required for sulfatase activity. Mutations cause multiple sulfatase deficiency, an autosomal recessive lysosomal storage disorder characterized by combined deficiency of all cellular sulfatases. The pathogenic mechanism involves loss of sulfatase activation, leading to accumulation of sulfated substrates and progressive neurodegeneration.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.071 OMIM phenotype
Clinical SummarySUMF1
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.31
OE 0.69 (0.461.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.50Z-score
OE missense 1.10 (0.981.22)
236 obs / 215.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.69 (0.461.07)
00.351.4
Missense OE1.10 (0.981.22)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 15 / 21.6Missense obs/exp: 236 / 215.4Syn Z: -0.76
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSUMF1-related multiple sulfatase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6261th %ile
GOF
0.6052th %ile
LOF
0.3453th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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