SUMO3

protein-coding

small ubiquitin like modifier 3

Gene summary

This gene encodes a member of the small ubiquitin-related modifier (SUMO) family of eukaryotic proteins. The encoded protein is covalently conjugated to other proteins via a post-translation modification known as sumoylation. Sumoylation may play a role in a wide variety of cellular processes, including nuclear transport, DNA replication and repair, mitosis, transcriptional regulation, and signal transduction. Alternatively spliced transcript variants encoding distinct proteins have been described. [provided by RefSeq, Feb 2014]

Previous symbols:

SMT3H1

MANE transcript

NM_006936.3

Inheritance

—

ClinVar variants

U:5B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr21:44,805,617-44,818,779

External References & Databases

Ensembl (ENSG00000184900)

Transcript & Mutation Effects

hg38 • Region Span ~13.2 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 SUMO3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 6

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006936.3. 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						0
missense			5 clinvar	1 clinvar	1 clinvar	7
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	5	1	1	7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006936.3	RefSeq	NP_008867.2	4	MANE Select
ENST00000332859.11	Ensembl	ENSP00000330343.7	4	MANE Select
NM_001286416.2	RefSeq	NP_001273345.1	4	Standard
ENST00000397893.3	Ensembl	ENSP00000380990.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
Fluid shear stress and atherosclerosis - Homo sapiens (human)
Exercise-induced Circadian Regulation
DNA Repair
SUMO is conjugated to E1 (UBA2:SAE1)

Biological Process

protein sumoylation
negative regulation of DNA binding

Molecular Function

protein binding
enzyme binding
protein tag
ubiquitin-like protein ligase binding

Cellular Component

kinetochore
nucleus
nucleoplasm
cytoplasm
PML body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332859
Coding exons: 4
Length: 13163
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125736
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	32	59.9	0.534	0.00000359	690
Missense (PolyPhen)		1	5.2279	0.19128		74
Synonymous	0.621	24	28.2	0.851	0.00000239	177
Loss of Function	1.47	1	4.29	0.233	1.83e-7	59

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an antagonist of ubiquitin in the degradation process. Plays a role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4 (PubMed:11451954, PubMed:18538659, PubMed:21965678). Plays a role in the regulation of sumoylation status of SETX (PubMed:24105744). {ECO:0000269|PubMed:11451954, ECO:0000269|PubMed:18538659, ECO:0000269|PubMed:21965678}.;

Intolerance Scores

LoFtool: 0.373
RVIS EVS: 0.24
RVIS percentile EVS: 68.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.948

Gene Damage Prediction

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