SUMO3

Chr 21

small ubiquitin like modifier 3

Also known as: SMT3A, SMT3H1, SUMO-3

The protein functions as a small ubiquitin-related modifier that is covalently attached to target proteins to regulate cellular processes including nuclear transport, DNA replication and repair, mitosis, and transcriptional regulation. Mutations in SUMO3 cause neurodevelopmental disorder with microcephaly, seizures, and brain atrophy with autosomal recessive inheritance. The gene shows moderate tolerance to loss-of-function variants.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
11
Pubs (1 yr)
93
P/LP submissions
P/LP missense
1.10
LOEUF
DN
Mechanism· predicted
Clinical SummarySUMO3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
88 unique Pathogenic / Likely Pathogenic· 21 VUS of 115 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.328
Z-score 1.47
OE 0.23 (0.081.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.28Z-score
OE missense 0.53 (0.400.72)
32 obs / 59.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.081.10)
00.351.4
Missense OE0.53 (0.400.72)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 1 / 4.3Missense obs/exp: 32 / 59.9Syn Z: 0.62
DN
0.6937th %ile
GOF
0.5169th %ile
LOF
0.4136th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

115 submitted variants in ClinVar

Classification Summary

Pathogenic84
Likely Pathogenic4
VUS21
Likely Benign1
Benign2
Conflicting1
84
Pathogenic
4
Likely Pathogenic
21
VUS
1
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
84
Likely Pathogenic
4
VUS
21
Likely Benign
1
Benign
2
Conflicting
1
Total113

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SUMO3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →