SUGT1

Chr 13

SGT1 assembly cochaperone of MIS12 kinetochore complex

Also known as: SGT1

NCBI Gene: 10910ENSG00000165416UniProt: Q9Y2Z0OMIM: 604098

The protein is involved in kinetochore function and cell cycle transitions at G1/S and G2/M checkpoints, and may participate in ubiquitin-mediated protein degradation. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain malformations. The gene shows significant constraint against loss-of-function variants (LOEUF 0.455), suggesting intolerance to protein disruption.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.46
Clinical Summary— SUGT1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 44 VUS of 134 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.453
Z-score 3.49
OE 0.22 (0.11–0.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.00Z-score
OE missense 0.78 (0.68–0.91)
134 obs / 170.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.11–0.46)
0≤0.351.4
Missense OE0.78 (0.68–0.91)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 5 / 23.1Missense obs/exp: 134 / 170.8Syn Z: -0.26
DN
0.6357th %ile
GOF
0.6247th %ile
LOF
0.3552th %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

134 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic2
VUS44
Likely Benign3
57
Pathogenic
2
Likely Pathogenic
44
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
57
0
57
Likely Pathogenic
0
0
2
0
2
VUS
0
33
11
0
44
Likely Benign
0
1
0
2
3
Benign
0
0
0
0
0
Total034702106

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SUGT1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients