SGO1

protein-coding

shugoshin 1

Gene summary

The protein encoded by this gene is a member of the shugoshin family of proteins. This protein is thought to protect centromeric cohesin from cleavage during mitotic prophase by preventing phosphorylation of a cohesin subunit. Reduced expression of this gene leads to the premature loss of centromeric cohesion, mis-segregation of sister chromatids, and mitotic arrest. Evidence suggests that this protein also protects a small subset of cohesin found along the length of the chromosome arms during mitotic prophase. An isoform lacking exon 6 has been shown to play a role in the cohesion of centrioles (PMID: 16582621 and PMID:18331714). Mutations in this gene have been associated with Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome, characterized by the co-occurrence of Sick Sinus Syndrome (SSS) and Chronic Intestinal Pseudo-obstruction (CIPO) within the first four decades of life (PMID:25282101). Fibroblast cells from CAID patients exhibited both increased cell proliferation and higher rates of senescence. Pseudogenes of this gene have been found on chromosomes 1 and 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

Previous symbols:

SGOL1

MANE transcript

NM_001199251.3

Inheritance

AR, AD

ClinVar variants

P:1U:11B:12

Top phenotype

Chronic atrial and intestinal dysrhythmia

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr3:20,160,593-20,186,206

External References & Databases

Ensembl (ENSG00000129810)

Transcript & Mutation Effects

hg38 • Region Span ~25.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

chronic atrial and intestinal dysrhythmiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014528

Submitter: PanelApp Australia

chronic atrial and intestinal dysrhythmiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014528

Submitter: Orphanet

chronic atrial and intestinal dysrhythmiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014528

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Chronic atrial and intestinal dysrhythmiaAD

Manifestation: Cardiovascular; Gastrointestinal

Intervention: Cardiovascular; Gastrointestinal

Rationale: The condition can involve arrthymias and valve anomalies, and awareness may allow early diagnosis and management (eg, with pacemakers); Individuals have been described with intestinal pseudoobstruction, and nutritional support, such as with TPN, has been described

Refs: 25282101

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SGO1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 12

not providedTotal: 6

SGO1-related disorderTotal: 4

Cardiovascular phenotypeTotal: 3

Chronic atrial and intestinal dysrhythmiaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001199251.3. 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			2 clinvar	1 clinvar	3 clinvar	6
missense	1 clinvar		6 clinvar	7 clinvar	1 clinvar	15
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	11	8	4	24

Highest pathogenic variant AF is 0.00016431928

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001199251.3	RefSeq	NP_001186180.1	7	MANE Select
ENST00000412997.6	Ensembl	ENSP00000410458.1	7	MANE Select
NM_001012409.4	RefSeq	NP_001012409.1	7	Standard
NM_001012410.5	RefSeq	NP_001012410.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sgo1	Danio rerio	Structure: pericardium Quality: edematous abnormal

Gene / Model

Organism

Observed Phenotype

sgo1

Danio rerio

Structure: pericardium

Quality: edematous

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oocyte meiosis - Homo sapiens (human)
Signal Transduction
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
Amplification of signal from the kinetochores
Mitotic Spindle Checkpoint

Biological Process

chromosome segregation
attachment of spindle microtubules to kinetochore
centriole-centriole cohesion
meiotic chromosome segregation
cell division

Molecular Function

protein binding
kinase binding

Cellular Component

chromosome, centromeric region
kinetochore
condensed chromosome kinetochore
condensed chromosome, centromeric region
spindle pole

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263753
Coding exons: 8
Length: 25700
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125725
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.577	305	278	1.10	0.0000137	3697
Missense (PolyPhen)		57	57.246	0.99571		811
Synonymous	-0.380	104	99.2	1.05	0.00000506	1013
Loss of Function	0.707	20	23.7	0.843	0.00000135	320

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000071	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00029	0.00027	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00031	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Isoform 3 plays a role in maintaining centriole cohesion involved in controlling spindle pole integrity. Involved in centromeric enrichment of AUKRB in prometaphase. {ECO:0000269|PubMed:15604152, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:15737064, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:20739936}.;
Disease: DISEASE: Chronic atrial and intestinal dysrhythmia (CAID) [MIM:616201]: A disease characterized by dysregulation of the cardiac sinus node resulting in sick sinus syndrome, in association with chronic intestinal pseudo-obstruction, a disorder of gastrointestinal motility in which intestinal obstruction occurs in the absence of a mechanical obstacle. {ECO:0000269|PubMed:25282101}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0775

Intolerance Scores

RVIS EVS: 0.71
RVIS percentile EVS: 85.68

Essentials

Essential (gene trap): E