SENP7

protein-coding

SUMO specific peptidase 7, the group of 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 many cellular processes. SUMO-specific proteases, such as SENP7, process SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also display isopeptidase activity for deconjugation of SUMO-conjugated substrates (Lima and Reverter, 2008 [PubMed 18799455]).[supplied by OMIM, Jun 2009]

MANE transcript

NM_020654.5

Inheritance

ClinVar variants

P:3U:107B:17

Top phenotype

arthrogryposis multiplex congenita

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr3:101,324,205-101,513,241

External References & Databases

Ensembl (ENSG00000138468)

Transcript & Mutation Effects

hg38 • Region Span ~189.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

arthrogryposis multiplex congenitaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015168

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SENP7 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 111

not providedTotal: 7

arthrogryposis multiplex congenita with neutropenia and early respiratory failureTotal: 1

SENP7-associated disorderTotal: 1

Arthrogryposis Multiplex Congenita and ImmunodeficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020654.5. 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 clinvar	1 clinvar	3
missense		1 clinvar	101 clinvar	12 clinvar	3 clinvar	117
nonsense	1 clinvar	1 clinvar				2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	1	2	107	13	4	127

Highest pathogenic variant AF is 6.2089356e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020654.5	RefSeq	NP_065705.3	24	MANE Select
ENST00000394095.7	Ensembl	ENSP00000377655.2	24	MANE Select
NM_001077203.3	RefSeq	NP_001070671.1	23	Standard
NM_001282801.2	RefSeq	NP_001269730.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein desumoylation

Molecular Function

protein binding
SUMO-specific endopeptidase activity

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394095
Coding exons: 24
Length: 189037
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125747
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.12	382	518	0.738	0.0000259	6881
Missense (PolyPhen)		80	169.47	0.47205		2294
Synonymous	1.76	158	189	0.837	0.00000956	1918
Loss of Function	5.45	15	60.9	0.246	0.00000340	773

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.000082	0.000079	rare
South Asian	0.000077	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protease that deconjugates SUMO2 and SUMO3 from targeted proteins, but not SUMO1. Catalyzes the deconjugation of poly-SUMO2 and poly-SUMO3 chains. Has very low efficiency in processing full- length SUMO proteins to their mature forms. {ECO:0000269|PubMed:18799455}.;

Recessive Scores

pRec: 0.0847

Intolerance Scores

LoFtool: 0.678
RVIS EVS: 0.49
RVIS percentile EVS: 79.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.140

Gene Damage Prediction

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