SUMF2

protein-coding

sulfatase modifying factor 2

Gene summary

The catalytic sites of sulfatases are only active if they contain a unique amino acid, C-alpha-formylglycine (FGly). The FGly residue is posttranslationally generated from a cysteine by enzymes with FGly-generating activity. The gene described in this record is a member of the sulfatase-modifying factor family and encodes a protein with a DUF323 domain that localizes to the lumen of the endoplasmic reticulum. This protein has low levels of FGly-generating activity but can heterodimerize with another family member - a protein with high levels of FGly-generating activity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_015411.4

Inheritance

—

ClinVar variants

P:1U:80B:5

Top phenotype

SUMF2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr7:56,064,002-56,080,670

External References & Databases

Ensembl (ENSG00000129103)

Transcript & Mutation Effects

hg38 • Region Span ~16.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUMF2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 4

SUMF2-related disorderTotal: 3

Multiple sulfatase deficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015411.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar			8
missense			61 clinvar	4 clinvar		65
nonsense			1 clinvar			1
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)	1 clinvar		10 clinvar			11
Total	1	0	80	4	1	86

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 99 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015411.4	RefSeq	NP_056226.3	9	MANE Select
ENST00000434526.8	Ensembl	ENSP00000400922.3	9	MANE Select
NM_001042468.3	RefSeq	NP_001035933.3	9	Standard
NM_001042469.3	RefSeq	NP_001035934.3	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Post-translational protein modification
Metabolism of proteins
The activation of arylsulfatases
Gamma carboxylation, hypusine formation and arylsulfatase activation

Biological Process

glycosphingolipid metabolic process
post-translational protein modification

Molecular Function

metal ion binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342190
Coding exons: 8
Length: 16669
Individuals with no LoFs: 125096
Homozygous LoFs: 12
Heterozygous LoFs: 639
Defined: 125747
p: 0.00259

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.526	223	202	1.10	0.0000105	2284
Missense (PolyPhen)		64	56.038	1.1421		628
Synonymous	-0.355	88	83.9	1.05	0.00000464	727
Loss of Function	0.695	14	17.1	0.819	8.92e-7	168

Population LoF Frequency

Population	CAF	p-value	Status
African	0.035	0.035	notable
Latino/Admixed American	0.0020	0.0020	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00013	0.00013	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Lacks formylglycine generating activity and is unable to convert newly synthesized inactive sulfatases to their active form. Inhibits the activation of sulfatases by SUMF1. {ECO:0000269|PubMed:12757706, ECO:0000269|PubMed:15708861, ECO:0000269|PubMed:15962010}.;

Recessive Scores

pRec: 0.687

Intolerance Scores

LoFtool: 0.0730
RVIS EVS: 0.42
RVIS percentile EVS: 77.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.685

Gene Damage Prediction

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