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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple sulfatase deficiency	AR	Audiologic/Otolaryngologic; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic	The 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 changes	Audiologic/Otolaryngologic; Biochemical; Cardiovascular; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic	14476546; 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 (60 variants)
• not provided (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	192	2	196
missense	3	16	168	3	5	195
nonsense	26	2	1			29
start loss	2	1				3
frameshift	23	3	1			27
inframe indel			2			2
splice donor/acceptor (+/-2bp)	4	17		1		22
splice region	2		6	31	1	40
non coding			28	116	32	176
Total	58	39	202	312	39

Highest pathogenic variant AF is 0.0000197

Variants in SUMF1

This is a list of pathogenic ClinVar variants found in the SUMF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-3844731-T-C			Likely benign (Jul 16, 2018)
3-3844734-G-C		not specified	Uncertain significance (Jun 09, 2022)
3-3844798-G-A		not specified	Uncertain significance (Mar 25, 2024)
3-3844817-A-G		not specified	Uncertain significance (Nov 19, 2022)
3-3844928-A-C		not specified	Uncertain significance (Dec 20, 2023)
3-3844978-G-C		not specified	Uncertain significance (Jun 11, 2024)
3-3845037-C-T			Benign (Dec 31, 2019)
3-3845092-A-C		not specified	Uncertain significance (Jun 09, 2022)
3-3845100-C-T			Benign (Dec 31, 2019)
3-3845122-C-A		not specified	Likely benign (Dec 08, 2023)
3-3845131-G-T		not specified	Likely benign (Aug 21, 2023)
3-3845212-C-T		not specified	Uncertain significance (Dec 14, 2023)
3-3845230-A-C		not specified	Uncertain significance (Feb 06, 2024)
3-3845264-A-T		not specified	Uncertain significance (Jun 29, 2023)
3-3845404-C-T		not specified	Uncertain significance (May 09, 2024)
3-3845471-A-G		not specified	Uncertain significance (Feb 14, 2023)
3-3845499-G-A		not specified	Uncertain significance (Mar 01, 2024)
3-3845558-A-G		not specified	Uncertain significance (May 18, 2023)
3-3845589-G-C		not specified	Uncertain significance (Apr 20, 2023)
3-3845625-C-T			Likely benign (Mar 01, 2023)
3-3845629-C-G		not specified	Uncertain significance (Jan 30, 2024)
3-3845704-A-G		not specified	Uncertain significance (May 08, 2024)
3-3845731-C-T		not specified	Uncertain significance (Aug 16, 2021)
3-3845793-C-T			Likely benign (Apr 16, 2018)
3-3845801-C-T		not specified	Uncertain significance (Jan 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SUMF1	protein_coding	protein_coding	ENST00000272902	9	766468

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.28e-8	0.704	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.499	236	215	1.10	0.0000116	2381
Missense in Polyphen		68	80.545	0.84425		941
Synonymous	-0.756	96	87.0	1.10	0.00000506	749
Loss of Function	1.31	15	21.6	0.695	0.00000109	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000725	0.000724
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000890	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.000392	0.000392
Other	0.00	0.00

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

Haploinsufficiency Scores

• pHI: 0.0288
• hipred: N
• hipred_score: 0.416
• ghis: 0.440

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

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

Mouse Genome Informatics

• Gene name: Sumf1
• Phenotype: growth/size/body region phenotype; cellular phenotype; craniofacial phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system phenotype

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