SENP3

protein-coding

SUMO specific peptidase 3, the group of Large ribosomal subunit biogenesis complex|SUMO specific peptidases

Gene summary

The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; MIM 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP3, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006 [PubMed 16738315]).[supplied by OMIM, Jun 2009]

MANE transcript

NM_015670.6

Inheritance

—

ClinVar variants

U:53B:1

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr17:7,561,919-7,571,969

External References & Databases

Ensembl (ENSG00000161956)

Transcript & Mutation Effects

hg38 • Region Span ~10.1 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 SENP3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 53

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015670.6. 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				1 clinvar		1
missense			53 clinvar			53
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	1	0	54

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015670.6	RefSeq	NP_056485.2	10	MANE Select
ENST00000321337.12	Ensembl	ENSP00000314029.8	10	MANE Select
ENST00000580231.5	Ensembl	ENSP00000463358.1	8	Standard
ENST00000581093.1	Ensembl	ENSP00000462461.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

rRNA processing
protein desumoylation

Molecular Function

protein binding
cysteine-type peptidase activity

Cellular Component

nucleus
nucleoplasm
nucleolus
cytoplasm
MLL1 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000429205
Coding exons: 11
Length: 10096
Individuals with no LoFs: 124629
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 124633
p: 0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.56	204	336	0.607	0.0000199	3676
Missense (PolyPhen)		32	85.231	0.37545		981
Synonymous	0.298	120	124	0.966	0.00000658	1157
Loss of Function	4.32	6	32.6	0.184	0.00000213	311

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000090	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates. Deconjugates SUMO2 from MEF2D, which increases its transcriptional activation capability. Deconjugates SUMO2 and SUMO3 from CDCA8. Redox sensor that, when redistributed into nucleoplasm, can act as an effector to enhance HIF1A transcriptional activity by desumoylating EP300. Required for rRNA processing through deconjugation of SUMO2 and SUMO3 from nucleophosmin, NPM1. Plays a role in the regulation of sumoylation status of ZNF148. Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. {ECO:0000269|PubMed:15743823, ECO:0000269|PubMed:16608850, ECO:0000269|PubMed:18259216, ECO:0000269|PubMed:18946085, ECO:0000269|PubMed:19015314, ECO:0000269|PubMed:19680224, ECO:0000269|PubMed:22872859}.;

Recessive Scores

pRec: 0.109

Essentials

Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.983

Gene Damage Prediction

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