GeneBe

SUMF1

sulfatase modifying factor 1

Basic information

Region (hg38): 3:3700814-4467273

Links

ENSG00000144455 ∙ NCBI:285362 ∙ OMIM:607939 ∙ HGNC:20376 ∙ Uniprot:Q8NBK3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • mucosulfatidosis (Definitive), mode of inheritance: AR
  • mucosulfatidosis (Strong), mode of inheritance: AR
  • mucosulfatidosis (Strong), mode of inheritance: AR
  • mucosulfatidosis (Strong), mode of inheritance: AR
  • mucosulfatidosis (Supportive), mode of inheritance: AR
  • mucosulfatidosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Multiple sulfatase deficiencyARAudiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; OphthalmologicThe condition can include hearing loss, and hearing testing has been recommended; Due to risk of cardiovascular sequelae, screening with electrocardiogram and echocardiogram has been recommended; Due to risk of gallbladder complications, radiologic screening has been recommended; Management guidlines include hip and spine imaging to screen for hip dysplasia and cervical spine instability; Due to risk of glaucoma, ophthalmologic screening and management has been recommended; As neurological complications have been described, urgent brain imaging has been recommended in the setting of acute neurologic changesAudiologic/Otolaryngologic; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic14476546; 11737681; 12757706; 12757705; 17657823; 18509892; 19066960; 19697114; 21224894; 29397290

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SUMF1 gene.

  • Multiple_sulfatase_deficiency (673 variants)
  • not_provided (61 variants)
  • Inborn_genetic_diseases (60 variants)
  • not_specified (16 variants)
  • SUMF1-related_disorder (11 variants)
  • See_cases (3 variants)
  • Spinocerebellar_ataxia_type_15/16 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SUMF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000182760.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
6
clinvar
211
clinvar
1
clinvar
 218
missense
6
clinvar
30
clinvar
196
clinvar
10
clinvar
4
clinvar
 246
nonsense
27
clinvar
8
clinvar
1
clinvar
 36
start loss
1
2
3
frameshift
24
clinvar
9
clinvar
1
clinvar
 34
splice donor/acceptor (+/-2bp)
4
clinvar
21
clinvar
1
clinvar
 26
Total 62 70 204 222 5

Highest pathogenic variant AF is 0.00017537446

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SUMF1protein_codingprotein_codingENST00000272902 9766468
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1257080401257480.000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.4992362151.100.00001162381
Missense in Polyphen6880.5450.84425941
Synonymous-0.7569687.01.100.00000506749
Loss of Function1.311521.60.6950.00000109232

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007250.000724
Ashkenazi Jewish0.000.00
East Asian0.0001090.000109
Finnish0.000.00
European (Non-Finnish)0.00008900.0000879
Middle Eastern0.0001090.000109
South Asian0.0003920.000392
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Oxidase that catalyzes the conversion of cysteine to 3- oxoalanine on target proteins, using molecular oxygen and an unidentified reducing agent (PubMed:12757706, PubMed:15657036, PubMed:15907468, PubMed:25931126, PubMed:16368756, PubMed:21224894). 3-oxoalanine modification, which is also named formylglycine (fGly), occurs in the maturation of arylsulfatases and some alkaline phosphatases that use the hydrated form of 3- oxoalanine as a catalytic nucleophile (PubMed:12757706, PubMed:15657036, PubMed:15907468, PubMed:25931126, PubMed:16368756). Known substrates include GALNS, ARSA, STS and ARSE (PubMed:12757706, PubMed:15907468, PubMed:15657036). {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15657036, ECO:0000269|PubMed:15907468, ECO:0000269|PubMed:16368756, ECO:0000269|PubMed:21224894, ECO:0000269|PubMed:25931126}.;
Disease
DISEASE: Multiple sulfatase deficiency (MSD) [MIM:272200]: A clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post- translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay. {ECO:0000269|PubMed:12757705, ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15146462, ECO:0000269|PubMed:18157819, ECO:0000269|PubMed:21224894}. Note=The disease is caused by mutations affecting the gene represented in this entry. SUMF1 mutations result in defective post-translational modification of sulfatases. {ECO:0000269|PubMed:12757706}.;
Pathway
Lysosome - Homo sapiens (human);Metabolism of lipids;Post-translational protein modification;Metabolism of proteins;The activation of arylsulfatases;Gamma carboxylation, hypusine formation and arylsulfatase activation;Metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

pRec
0.0660

Intolerance Scores

loftool
0.0554
rvis_EVS
-0.18
rvis_percentile_EVS
40.36

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.294

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Gene ontology

Biological process
glycosphingolipid metabolic process;protein oxidation;post-translational protein modification
Cellular component
endoplasmic reticulum;endoplasmic reticulum lumen
Molecular function
oxidoreductase activity;protein homodimerization activity;Formylglycine-generating oxidase activity;cupric ion binding
Feedback | API | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.