SGO2

Chr 2ADAR

shugoshin 2

Also known as: SGOL2, TRIPIN

NCBI Gene: 151246 ENSG00000163535 UniProt: Q562F6 OMIM: 612425

SGO2 encodes shugoshin 2, a protein that protects centromeric cohesin complexes during meiosis and is essential for accurate chromosome segregation during gametogenesis and mitosis. Mutations cause premature ovarian failure-5, an autosomal recessive disorder affecting female fertility. This gene is highly intolerant to loss-of-function variants, indicating it is under strong evolutionary constraint.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in meiotic sister chromatid cohesion. Predicted to act upstream of or within several processes, including meiotic nuclear division; meiotic sister chromatid cohesion; and positive regulation of maintenance of meiotic sister chromatid cohesion, centromeric. Located in chromosome, centromeric region and nuclear body. Part of mitotic cohesin complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismAD/ARLOEUF 0.652 OMIM phenotypes

Clinical Summary— SGO2

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 10 VUS of 32 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 3.35

OE 0.44 (0.30–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.56Z-score

OE missense 0.94 (0.87–1.00)

572 obs / 611.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.30–0.65)

0≤0.351.4

Missense OE?0.94 (0.87–1.00)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 18 / 41.3Missense obs/exp: 572 / 611.2Syn Z: 1.43

This gene — mechanism propensity

0.6258th %ile

GOF

0.3094th %ile

LOF

0.4726th %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

32 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS10

Likely Benign4

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	2	0	0	2
Likely Pathogenic	0	0	0	0
VUS	0	10	0	10
Likely Benign	0	4	0	4
Benign	0	2	1	3
Total	2	16	1	19

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 35) ClinVar copy-number / structural variants overlap SGO2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →