SUGT1

Chr 13

SGT1 assembly cochaperone of MIS12 kinetochore complex

Also known as: SGT1

NCBI Gene: 10910 ENSG00000165416 UniProt: Q9Y2Z0

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a highly conserved nuclear protein involved in kinetochore function and required for the G1/S and G2/M transitions. This protein interacts with heat shock protein 90. Alternative splicing results in multiple transcript variants. Pseudogenes for this gene have been defined on several different chromosomes. [provided by RefSeq, Mar 2016]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.22 (0.11–0.46)

0≤0.351.4

Missense OE?0.78 (0.68–0.91)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 5 / 23.1Missense obs/exp: 134 / 170.8Syn Z: -0.26

Background carrier burden — how many people carry a rare variant somewhere in SUGT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

391 rare PASS variants

Rare truncating (LoF)

1 in 2,300

46 rare PASS variants

Rare synonymous (reference)

1 in 270

145 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SUGT1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 290	1 in 4,100
South Asian	~43k	1 in 100	1 in 4,100
Remaining (unassigned)	~30k	1 in 280	1 in 830
European (Finnish)	~27k	1 in 400	none seen
Admixed American	~22k	1 in 300	≈ 1 in 17,000
African / African American	~21k	1 in 140	1 in 1,500
East Asian	~20k	1 in 170	1 in 1,100
Ashkenazi Jewish	~13k	1 in 380	none seen
Middle Eastern	~2,884	1 in 360	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 13 coding exons well covered in gnomAD exomes; exons 5, 9, 10, 13 marginal. Genomes: all 13.? see exons ↓