SGO1

Summary

SGO1 (shugoshin 1, HGNC:25088) is a protein-coding gene on chromosome 3p24.3, encoding Shugoshin 1 (Q5FBB7). 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. It is a common-essential gene (DepMap: required in 91.5% of cancer cell lines).

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.

Source: NCBI Gene 151648 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chronic atrial and intestinal dysrhythmia (Moderate, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 35 total — 1 pathogenic
• Phenotypes (HPO): 15
• Cancer dependency (DepMap): dependent in 91.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_001199251

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25088
Approved symbol	SGO1
Name	shugoshin 1
Location	3p24.3
Locus type	gene with protein product
Status	Approved
Aliases	NY-BR-85
Ensembl gene	ENSG00000129810
Ensembl biotype	protein_coding
OMIM	609168
Entrez	151648

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 21 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000263753, ENST00000306698, ENST00000412997, ENST00000417364, ENST00000419233, ENST00000421451, ENST00000425061, ENST00000437051, ENST00000442720, ENST00000443724, ENST00000452020, ENST00000456624, ENST00000460637, ENST00000860144, ENST00000860145, ENST00000924914, ENST00000924915, ENST00000924916, ENST00000924917, ENST00000924918, ENST00000924919, ENST00000924920, ENST00000924921

RefSeq mRNA: 13 — MANE Select: NM_001199251 NM_001012409, NM_001012410, NM_001012411, NM_001012412, NM_001012413, NM_001199251, NM_001199252, NM_001199253, NM_001199254, NM_001199255, NM_001199256, NM_001199257, NM_138484

CCDS: CCDS2635, CCDS33716, CCDS46771, CCDS46772, CCDS46773, CCDS46774, CCDS56243

Canonical transcript exons

ENST00000412997 — 8 exons

Exon	Start	End
ENSE00000891421	20174249	20175055
ENSE00001076243	20171043	20171232
ENSE00001076247	20183608	20183804
ENSE00001162359	20183886	20184034
ENSE00001615074	20169484	20170815
ENSE00001757509	20185948	20186206
ENSE00003653589	20178271	20178347
ENSE00003678419	20176601	20176659

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 92.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.3211 / max 172.4219, expressed in 1238 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41421	7.1281	1196
41423	0.9349	564
41422	0.2168	105
41420	0.0412	16

Top tissues by expression

247 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.29	gold quality
ventricular zone	UBERON:0003053	89.69	gold quality
buccal mucosa cell	CL:0002336	89.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.33	gold quality
ganglionic eminence	UBERON:0004023	84.40	gold quality
embryo	UBERON:0000922	84.39	gold quality
bone marrow cell	CL:0002092	75.94	gold quality
secondary oocyte	CL:0000655	75.74	silver quality
stromal cell of endometrium	CL:0002255	72.20	gold quality
vermiform appendix	UBERON:0001154	71.57	gold quality
mucosa of transverse colon	UBERON:0004991	70.73	gold quality
rectum	UBERON:0001052	70.67	gold quality
lymph node	UBERON:0000029	69.55	gold quality
tendon of biceps brachii	UBERON:0008188	68.92	gold quality
bone marrow	UBERON:0002371	68.22	gold quality
thymus	UBERON:0002370	67.54	silver quality
testis	UBERON:0000473	67.44	gold quality
adrenal tissue	UBERON:0018303	67.25	gold quality
left testis	UBERON:0004533	66.36	gold quality
right testis	UBERON:0004534	66.24	gold quality
caecum	UBERON:0001153	65.60	gold quality
lower esophagus mucosa	UBERON:0035834	64.38	gold quality
esophagus mucosa	UBERON:0002469	64.31	gold quality
oocyte	CL:0000023	63.42	silver quality
smooth muscle tissue	UBERON:0001135	63.11	gold quality
leukocyte	CL:0000738	62.16	gold quality
monocyte	CL:0000576	61.98	gold quality
tonsil	UBERON:0002372	61.52	gold quality
tendon	UBERON:0000043	61.42	gold quality
calcaneal tendon	UBERON:0003701	60.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ENAD-17	yes	162.37
E-HCAD-10	yes	25.22
E-ANND-3	yes	5.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting SGO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-8070	99.07	69.30	1303

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Bub1 protects centromeric cohesion through Shugoshin in mitosis (PMID:15604152)
• A shugoshin-like protein associates with centromeres during prophase and disappears at the onset of anaphase (PMID:15737064)
• A comprehensive review of Sgo1 function in eukaryote at meiosis and mitosis. (PMID:16112668)
• a specific subtype of serine/threonine protein phosphatase 2A (PP2A) associates with human shugoshin (PMID:16541025)
• Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting Plk1-mediated chromosome removal of Sgo1. (PMID:16580887)
• depletion of Sgo1 results in precocious chromosomal segregation and massive mitotic arrest (PMID:16628005)
• Mutation in the SGOL1 D-box causes transient metaphase arrest, and leads to defects in chromosome alignment and segregation. (PMID:17448445)
• Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1. (PMID:17617734)
• Results suggest that NEK2A-mediated phosphorylation of Sgo1 (SGOL1) provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores. (PMID:17621308)
• Centriole splitting induced by Sgo1 depletion or expression of a dominant negative mutant is suppressed by ectopic expression of sSgo1 or by Plk1 knockdown. (PMID:18331714)
• findings suggest that hSgo1-downregulated colorectal cancers have a clinicopathological character of chromosome instability (CIN), and hSgo1 downregulation leads to CIN in colorectal cancer cells. (PMID:18635744)
• the direct link between HP1 and shugoshin is conserved in human cells (PMID:18716626)
• the spindle checkpoint kinase Bub1 contributes to the maintenance of Sgo1 steady-state protein levels in an APC/C-independent mechanism. (PMID:19015261)
• Report structure and function of the PP2A-shugoshin interaction. (PMID:19716788)
• Data show that human germinal center-associated nuclear protein (GANP) is critically involved in cell proliferation at the mitotic phase through its selective support of shugoshin-1 mRNA export. (PMID:20384790)
• HP1alpha binding by INCENP or Shugoshin 1 (Sgo1) is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet unknown interphase functions of the chromosome passenger complex (CPC) or Sgo1 at the centromeres. (PMID:21346195)
• These results suggest that SGOL1-P1 may function as a negative factor to native SGOL1, and that abundant expression of SGOL1-P1 may be responsible for chromosomal instability. (PMID:21532624)
• Lentivirus-mediated siRNA interference targeting SGO-1 inhibits human NSCLC cell growth (PMID:22161216)
• SGO1 promotes multidrug resistance of gastric cancer cells and may be useful as a novel therapeutic target for preventing or reversing multidrug resistance (PMID:23564482)
• Frameshift mutations of SGOL1 and PDS5B and the loss of their expression may be a feature of gastric and colorectal cancers with high microsatellite instability. (PMID:23850494)
• The most significant association with MaxDrinks was observed with SNP rs11128951 (p = 4.27 x 10(-8)) near SGOL1 gene at 3p24.3. (PMID:23953852)
• Bub1-mediated H2A phosphorylation penetrates kinetochores and that this histone mark contributes to a tension-sensitive Sgo1-based molecular switch for chromosome segregation. (PMID:24055156)
• SGOL1 variant B induces abnormal mitosis and resistance to taxane in non-small cell lung cancers. (PMID:24146025)
• Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. (PMID:25282101)
• Aurora B kinase interacts with and phosphorylates Sgo1. Aurora B-mediated phosphorylation of Sgo1 regulates the distribution of Sgo1 between centromeres and chromosome arms. (PMID:25451264)
• Data indicate essential role of shugoshin-like protein 1 (Sgo1) in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for hepatocellular carcinoma (HCC). (PMID:25638162)
• our findings strongly suggest that CIP2A promotes cell cycle progression, premature chromosome segregation, and aneuploidy, possibly through a novel interaction with Sgol1. (PMID:25736928)
• Sgo1 co-recruits Aurora B and PP2A to centromeres of unattached chromosomes. (PMID:25892238)
• Results show that Sgo1 is first recruited to kinetochores by H2A-pT120, and the kinetochore-bound Sgo1 is released by centromeric transcription. (PMID:26190260)
• Cohesin complex is shown to be a target of the prophase pathway at centrosomes and protected by Sgo1-dependent PP2A recruitment. (PMID:26365192)
• Molecular chaperone SET-assisted eviction of linker histones and Shugoshins is a fundamental step in mammalian mitotic progression. (PMID:28781233)
• Many factors involved in the chromatin association of Shugoshin proteins are well established, most strikingly through modifications found directly on centromeric and pericentric chromatin. It has been well established that phosphorylation at the centromere is essential to nucleating Shugoshin recruitment. (PMID:29796904)
• Shugoshin-1 (Sgo1) protects the integrity of the centromeres, and H2A phosphorylation is critical for this process. (PMID:30212568)
• A major function of RSF1 is to recruit HDAC1 to centromeres, where it antagonizes Tip60-mediated acetylation of H2A- K118, which allows Sgo1 accumulation and centromeric cohesion protection. (PMID:30242288)
• noncanonical roles of SGO1 drive the clinical manifestations observed in chronic atrial and intestinal dysrhythmia. (PMID:30739867)
• Transcript amounts of SGO1-AS1 could distinguish these two sets of samples. (PMID:31156154)
• a major function of SET during mitosis is to disrupt the Sgo1-cohesin interaction. (PMID:31227592)
• Cohesin-protein Shugoshin-1 controls cardiac automaticity via HCN4 pacemaker channel. (PMID:33953173)
• A highly conserved pocket on PP2A-B56 is required for hSgo1 binding and cohesion protection during mitosis. (PMID:33973335)
• Prognosis and biological function of SGOL1 in clear cell renal cell carcinoma: a multiomics analysis. (PMID:38383432)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgo1	ENSDARG00000103907
mus_musculus	Sgo1	ENSMUSG00000023940
rattus_norvegicus	Sgo1	ENSRNOG00000022499

Paralogs (1): SGO2 (ENSG00000163535)

Protein

Protein identifiers

Shugoshin 1 — Q5FBB7 (reviewed: Q5FBB7)

Alternative names: Serologically defined breast cancer antigen NY-BR-85, Shugoshin-like 1

All UniProt accessions (3): Q5FBB7, B5BUA4, F8WB17

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with PPP2CA (or PPP2CB), PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E, SET, LRRC59, RBM10 (or RBM5), RPL10A, RPL28, RPL7, RPL7A and RPLP1. Interaction with protein phosphatase 2A occurs most probably through direct binding to the regulatory B56 subunits: PPP2R1B, PPP2R5A, PPP2R5B, PPP2R5C, PPP2R5D, PPP2R5E. Interacts with PPP2R1A and NEK2. Isoform 3 interacts with PLK1. Interacts with CDCA8.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore. Cytoplasm. Cytoskeleton. Spindle pole. Microtubule organizing center. Centrosome. Nucleus speckle.

Tissue specificity. Widely expressed. Highly expressed in testis. Expressed in lung, small intestine, breast, liver and placenta. Strongly overexpressed in 90% of breast cancers tested.

Post-translational modifications. Ubiquitinated and degraded during mitotic exit by APC/C-Cdh1. Phosphorylation by NEK2 is essential for chromosome congression in mitosis and for the proper attachment of spindle microtubule to the kinetochore. Phosphorylated by PLK1 and AUKRB.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The KEN box and D-box 3 are required for its ubiquitination and degradation.

Miscellaneous. Shugoshin is Japanese for guardian spirit (as it is known to be a protector of centromeric cohesin).

Similarity. Belongs to the shugoshin family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q5FBB7-1	1, 1EF, SgoL1-A2	yes
Q5FBB7-2	2, 1GH, SgoL1-B2
Q5FBB7-3	3, 1KL, sSGO1, SgoL1-C2
Q5FBB7-4	4, 1CD, SgoL1-B1
Q5FBB7-5	5, 1AB, SgoL1-C1
Q5FBB7-6	6, 1AB, SgoL1-A1
Q5FBB7-7	7, 1J

RefSeq proteins (13): NP_001012409, NP_001012410, NP_001012411, NP_001012412, NP_001012413, NP_001186180, NP_001186181, NP_001186182, NP_001186183, NP_001186184, NP_001186185, NP_001186186, NP_612493 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011515	Shugoshin_C	Domain
IPR011516	Shugoshin_N	Domain
IPR038889	Shugoshin1/2	Family

Pfam: PF07557, PF07558

UniProt features (44 total): mutagenesis site 9, compositionally biased region 7, splice variant 6, short sequence motif 5, modified residue 4, region of interest 3, sequence variant 3, coiled-coil region 2, helix 2, strand 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3Q6S	X-RAY DIFFRACTION	1.93
4A0I	X-RAY DIFFRACTION	2.6
3FGA	X-RAY DIFFRACTION	2.7
7ZJS	X-RAY DIFFRACTION	3.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5FBB7-F1	55.49	0.11

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 14, 256, 436, 507

Mutagenesis-validated functional residues (9):

Position	Phenotype
14	loss of phosphorylation and presence of misaligned chromosomes; when associated with a-507.
61	loss of interaction with ppp2ca and ppp2r1a and loss of centromeric localization.
73	loss of proper localization to spindle pole and mitotic spindle. significant increase in split spindle poles.
146	loss of proper localization to spindle pole and mitotic spindle. significant increase in split spindle poles.
451	disrupts interaction with cbx5, loss of localization to centromeres in interphase, no effect on localization to centrome
453	disrupts interaction with cbx5, loss of localization to centromeres in interphase, no effect on localization to centrome
455	disrupts interaction with cbx5, loss of localization to centromeres in interphase, no effect on localization to centrome
492	loss of centromeric localization.
507	loss of phosphorylation; and presence of misaligned chromosomes; when associated with a-14.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 282 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_CHROMOSOME_LOCALIZATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ORGANELLE_FISSION, PID_PLK1_PATHWAY, FISCHER_G2_M_CELL_CYCLE, GOBP_SISTER_CHROMATID_COHESION, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN, USF_01, GOCC_CENTROSOME, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, PID_AURORA_B_PATHWAY, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (6): chromosome segregation (GO:0007059), attachment of spindle microtubules to kinetochore (GO:0008608), centriole-centriole cohesion (GO:0010457), meiotic chromosome segregation (GO:0045132), cell division (GO:0051301), mitotic sister chromatid cohesion, centromeric (GO:0071962)

GO Molecular Function (2): kinase binding (GO:0019900), protein binding (GO:0005515)

GO Cellular Component (12): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), condensed chromosome, centromeric region (GO:0000779), spindle pole (GO:0000922), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), nuclear speck (GO:0016607), nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
G2/M Transition	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell cycle process	3
intracellular membraneless organelle	3
microtubule binding	1
metaphase chromosome alignment	1
centrosome cycle	1
nuclear chromosome segregation	1
meiotic nuclear division	1
meiotic cell cycle process	1
cellular process	1
mitotic sister chromatid cohesion	1
centromeric sister chromatid cohesion	1
enzyme binding	1
binding	1
chromosomal region	1
condensed chromosome, centromeric region	1
supramolecular complex	1
chromosome, centromeric region	1
condensed chromosome	1
spindle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGO1	CDCA8	Q53HL2	966
SGO1	SGO2	Q562F6	966
SGO1	BUB1	O43683	938
SGO1	H2AC19	P20670	929
SGO1	REC8	O95072	918
SGO1	RAD21	O60216	917
SGO1	H2AC20	Q16777	915
SGO1	AURKB	Q96GD4	912
SGO1	ESPL1	Q14674	894
SGO1	STAG2	Q8N3U4	874
SGO1	CDC20	Q12834	852
SGO1	SMC3	Q9UQE7	822
SGO1	PPP2R1A	P30153	802
SGO1	CDCA5	Q96FF9	801
SGO1	PTTG1	O95997	789

IntAct

55 interactions, top by confidence:

A	B	Type	Score
SMC1A	RAD21	psi-mi:“MI:0914”(association)	0.930
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
SGO1	PPP2CA	psi-mi:“MI:0915”(physical association)	0.850
SMC1A	PDS5A	psi-mi:“MI:0914”(association)	0.800
SGO1	STAG2	psi-mi:“MI:0915”(physical association)	0.770
STAG2	SGO1	psi-mi:“MI:0915”(physical association)	0.770
PPP2R5D	SGO1	psi-mi:“MI:0915”(physical association)	0.750
SGO1	CBX5	psi-mi:“MI:0915”(physical association)	0.740
SGO1	CBX5	psi-mi:“MI:0914”(association)	0.740
SGO1	RAD21	psi-mi:“MI:0914”(association)	0.740
RAD21	SGO1	psi-mi:“MI:0915”(physical association)	0.740
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
PPP2R5A	SGO1	psi-mi:“MI:0915”(physical association)	0.730
SGO1	PPP2R5A	psi-mi:“MI:0403”(colocalization)	0.730
PPP2R1A	PPFIA3	psi-mi:“MI:0914”(association)	0.670
CBX3	E2F6	psi-mi:“MI:0914”(association)	0.640
SGO1	SMC1A	psi-mi:“MI:0914”(association)	0.610
SMC1A	SGO1	psi-mi:“MI:0915”(physical association)	0.610
SGO1	SMC1A	psi-mi:“MI:0915”(physical association)	0.610
SGO1	CDCA5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (146): SGOL1 (Affinity Capture-MS), SGOL1 (Proximity Label-MS), ALDH1B1 (Affinity Capture-MS), CTSC (Affinity Capture-MS), DNMT3B (Affinity Capture-MS), ECH1 (Affinity Capture-MS), HNRNPAB (Affinity Capture-MS), LIMS1 (Affinity Capture-MS), PFDN2 (Affinity Capture-MS), RAD51 (Affinity Capture-MS), SET (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), DYSF (Affinity Capture-MS), CHD1L (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2UEI8, A0JNH9, A2BIL8, A8PUI7, B1H1S4, B2GUZ2, E7FAP1, E9Q309, F1R983, O60284, P49452, P51960, P86345, Q0P5H2, Q3T0A6, Q3T8J9, Q4KLP8, Q4QY64, Q4R731, Q535K8, Q563C3, Q58EL7, Q5FBB7, Q5QJE6, Q5VT06, Q5XG21, Q65Z40, Q6KAQ7, Q6NWJ0, Q6P0N0, Q6P6I6, Q76FK4, Q7YQM1, Q7YQM2, Q80WQ8, Q8C263, Q8C551, Q8IYH5, Q8NA57, Q8R2M2

Diamond homologs: Q5FBB7, Q9CXH7

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
PPP2R1A	up-regulates	SGO1	binding
NEK2	up-regulates	SGO1	phosphorylation
H2AC11	“up-regulates activity”	SGO1	relocalization
CDK1	“up-regulates activity”	SGO1	phosphorylation
SGO1	“up-regulates quantity by stabilization”	“Cohesin complex”	binding
BUB1	“up-regulates quantity by stabilization”	SGO1	phosphorylation
AURKA	“up-regulates activity”	SGO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by GSK3beta mutants	5	122.8×	7e-09
CTNNB1 S33 mutants aren’t phosphorylated	5	122.8×	7e-09
CTNNB1 S37 mutants aren’t phosphorylated	5	122.8×	7e-09
CTNNB1 S45 mutants aren’t phosphorylated	5	122.8×	7e-09
CTNNB1 T41 mutants aren’t phosphorylated	5	122.8×	7e-09
Beta-catenin phosphorylation cascade	5	108.3×	1e-08
Platelet sensitization by LDL	5	108.3×	1e-08
Co-inhibition by CTLA4	5	83.7×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
mitotic cell cycle	5	17.6×	4e-04
cell division	8	9.7×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

35 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	4
Likely benign	9
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
162627	NM_001199251.3(SGO1):c.67A>G (p.Lys23Glu)	Pathogenic

SpliceAI

1323 predictions. Top by Δscore:

Variant	Effect	Δscore
3:20170722:A:AC	donor_gain	1.0000
3:20170723:C:CC	donor_gain	1.0000
3:20171041:A:AC	donor_gain	1.0000
3:20171042:C:CC	donor_gain	1.0000
3:20171042:CG:C	donor_gain	1.0000
3:20171042:CGA:C	donor_gain	1.0000
3:20171042:CGAA:C	donor_gain	1.0000
3:20171042:CGAAG:C	donor_gain	1.0000
3:20171233:C:CC	acceptor_gain	1.0000
3:20176661:T:C	acceptor_gain	1.0000
3:20176671:CCAA:C	acceptor_gain	1.0000
3:20176672:CAA:C	acceptor_gain	1.0000
3:20176673:A:T	acceptor_gain	1.0000
3:20176674:A:AC	acceptor_gain	1.0000
3:20176674:A:C	acceptor_gain	1.0000
3:20178269:A:AC	donor_gain	1.0000
3:20178270:C:CC	donor_gain	1.0000
3:20182412:A:C	donor_gain	1.0000
3:20183694:G:C	donor_gain	1.0000
3:20183800:GTTGG:G	acceptor_gain	1.0000
3:20183801:TTGG:T	acceptor_gain	1.0000
3:20183802:TGG:T	acceptor_gain	1.0000
3:20183803:GG:G	acceptor_gain	1.0000
3:20183805:C:CC	acceptor_gain	1.0000
3:20183882:TTA:T	donor_loss	1.0000
3:20183883:TACT:T	donor_loss	1.0000
3:20183884:A:AC	donor_gain	1.0000
3:20183885:C:CA	donor_gain	1.0000
3:20183885:CT:C	donor_gain	1.0000
3:20183885:CTG:C	donor_gain	1.0000

AlphaMissense

3508 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:20170806:T:A	R494S	0.994
3:20170806:T:G	R494S	0.994
3:20170807:C:G	R494T	0.991
3:20170803:T:A	R495S	0.990
3:20170803:T:G	R495S	0.990
3:20170776:A:C	F504L	0.989
3:20170776:A:T	F504L	0.989
3:20170778:A:G	F504L	0.989
3:20170791:A:C	F499L	0.989
3:20170791:A:T	F499L	0.989
3:20170793:A:G	F499L	0.989
3:20170810:A:G	L493P	0.989
3:20170812:T:A	K492N	0.989
3:20170812:T:G	K492N	0.989
3:20183715:C:G	A78P	0.989
3:20170798:T:C	D497G	0.988
3:20183693:A:G	L85P	0.988
3:20183756:A:G	L64S	0.986
3:20183748:C:G	A67P	0.984
3:20183971:C:A	K19N	0.984
3:20183971:C:G	K19N	0.984
3:20170801:C:T	G496E	0.983
3:20170814:T:C	K492E	0.983
3:20170802:C:G	G496R	0.982
3:20170802:C:T	G496R	0.982
3:20174487:G:C	F348L	0.982
3:20174487:G:T	F348L	0.982
3:20174489:A:G	F348L	0.982
3:20170801:C:A	G496V	0.981
3:20170777:A:G	F504S	0.980

dbSNP variants (sampled 300 via entrez): RS1000121206 (3:20182675 G>A), RS1000142045 (3:20188584 T>C), RS1000149855 (3:20168309 C>A,T), RS1000216569 (3:20182464 G>C), RS1000268022 (3:20180768 C>T), RS1000330837 (3:20186365 G>A), RS1000378532 (3:20170158 G>A), RS1000442845 (3:20176232 C>T), RS1000614795 (3:20175952 T>C), RS1000873371 (3:20182092 A>C), RS1000966733 (3:20175716 G>A), RS1001134151 (3:20181370 A>C), RS1001138137 (3:20186397 C>A,G,T), RS1001164831 (3:20163465 G>C), RS1001227369 (3:20181116 C>T)

Disease associations

OMIM: gene MIM:609168 | disease phenotypes: MIM:616201

GenCC curated gene-disease

Disease	Classification	Inheritance
chronic atrial and intestinal dysrhythmia	Moderate	Autosomal recessive

Mondo (1): chronic atrial and intestinal dysrhythmia (MONDO:0014528)

Orphanet (1): Chronic atrial and intestinal dysrhythmia syndrome (Orphanet:435988)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001508	Failure to thrive
HP:0001642	Pulmonic stenosis
HP:0001647	Bicuspid aortic valve
HP:0001653	Mitral regurgitation
HP:0001662	Bradycardia
HP:0003621	Juvenile onset
HP:0004325	Decreased body weight
HP:0004389	Intestinal pseudo-obstruction
HP:0004749	Atrial flutter
HP:0005110	Atrial fibrillation
HP:0005155	Ventricular escape rhythm
HP:0011462	Young adult onset
HP:0011704	Sick sinus syndrome
HP:0031295	Left atrial enlargement

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001419_8	Temperament (bipolar disorder)	2.000000e-06
GCST002481_9	Acne (severe)	1.000000e-07
GCST003181_1	Staphylococcus aureus nasal carriage (intermittent)	9.000000e-09
GCST008749_3	Systolic blood pressure	1.000000e-06
GCST009391_734	Metabolite levels	8.000000e-06
GCST010988_133	Adult body size	9.000000e-09
GCST90002386_540	High light scatter reticulocyte percentage of red cells	4.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0007758	intermittent Staphylococcus aureus carrier status
EFO:0006335	systolic blood pressure
EFO:0009774	serine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	increases abundance, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
polyhexamethyleneguanidine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.