STAG1

Summary

STAG1 (STAG1 cohesin complex component, HGNC:11354) is a protein-coding gene on chromosome 3q22.3, encoding Cohesin subunit SA-1 (Q8WVM7). Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication.

This gene is a member of the SCC3 family and is expressed in the nucleus. It encodes a component of cohesin, a multisubunit protein complex that provides sister chromatid cohesion along the length of a chromosome from DNA replication through prophase and prometaphase, after which it is dissociated in preparation for segregation during anaphase.

Source: NCBI Gene 10274 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 703 total — 20 pathogenic, 33 likely-pathogenic
• MANE Select transcript: NM_005862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11354
Approved symbol	STAG1
Name	STAG1 cohesin complex component
Location	3q22.3
Locus type	gene with protein product
Status	Approved
Aliases	SA-1, SCC3A, SA1
Ensembl gene	ENSG00000118007
Ensembl biotype	protein_coding
OMIM	604358
Entrez	10274

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000236698, ENST00000383202, ENST00000434713, ENST00000462818, ENST00000465961, ENST00000480733, ENST00000483235, ENST00000487065, ENST00000492318, ENST00000629124, ENST00000862964, ENST00000862965, ENST00000862966, ENST00000862967, ENST00000862968, ENST00000862969, ENST00000968452, ENST00000968453, ENST00000968454, ENST00000968455, ENST00000968456

RefSeq mRNA: 1 — MANE Select: NM_005862 NM_005862

CCDS: CCDS3090

Canonical transcript exons

ENST00000383202 — 34 exons

Exon	Start	End
ENSE00001789840	136363366	136363467
ENSE00001864870	136336236	136338277
ENSE00001935236	136752195	136752378
ENSE00003459034	136477289	136477412
ENSE00003461754	136338370	136338450
ENSE00003461853	136521213	136521417
ENSE00003465089	136417885	136417972
ENSE00003465215	136349158	136349363
ENSE00003466592	136422410	136422613
ENSE00003466828	136421093	136421163
ENSE00003492585	136473539	136473637
ENSE00003501414	136472413	136472492
ENSE00003503782	136422952	136423044
ENSE00003511359	136604309	136604473
ENSE00003514501	136359148	136359296
ENSE00003529370	136542119	136542195
ENSE00003538964	136502628	136502779
ENSE00003551471	136369108	136369282
ENSE00003583464	136422768	136422857
ENSE00003591778	136623146	136623248
ENSE00003595769	136433556	136433659
ENSE00003605608	136340491	136340605
ENSE00003613831	136443287	136443404
ENSE00003629098	136357720	136357848
ENSE00003642663	136452033	136452147
ENSE00003648147	136366943	136367082
ENSE00003653649	136500223	136500296
ENSE00003654340	136343832	136344006
ENSE00003657496	136464881	136464988
ENSE00003658408	136377660	136377752
ENSE00003662307	136630870	136630981
ENSE00003664056	136398749	136398829
ENSE00003687182	136341441	136341551
ENSE00003693454	136568765	136568861

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7611 / max 420.2623, expressed in 1765 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44739	15.1022	1758
44738	0.3491	180
44740	0.2960	111
44731	0.0137	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.01	gold quality
parotid gland	UBERON:0001831	94.68	gold quality
sural nerve	UBERON:0015488	94.30	gold quality
tendon	UBERON:0000043	93.78	gold quality
ventricular zone	UBERON:0003053	92.82	gold quality
synovial joint	UBERON:0002217	92.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.71	gold quality
cauda epididymis	UBERON:0004360	91.70	gold quality
ganglionic eminence	UBERON:0004023	91.67	gold quality
pericardium	UBERON:0002407	91.66	gold quality
superficial temporal artery	UBERON:0001614	91.60	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.40	gold quality
secondary oocyte	CL:0000655	91.22	gold quality
saphenous vein	UBERON:0007318	91.10	gold quality
caput epididymis	UBERON:0004358	90.97	gold quality
colonic epithelium	UBERON:0000397	90.85	gold quality
urethra	UBERON:0000057	90.55	gold quality
bone marrow cell	CL:0002092	90.51	gold quality
biceps brachii	UBERON:0001507	90.28	gold quality
oocyte	CL:0000023	90.23	gold quality
corpus epididymis	UBERON:0004359	90.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.61	gold quality
embryo	UBERON:0000922	89.47	gold quality
adrenal tissue	UBERON:0018303	89.28	gold quality
colonic mucosa	UBERON:0000317	89.12	gold quality
mucosa of urinary bladder	UBERON:0001259	89.10	gold quality
mammary duct	UBERON:0001765	89.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.05	gold quality
heart right ventricle	UBERON:0002080	88.94	gold quality
epithelium of mammary gland	UBERON:0003244	88.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.13
E-MTAB-6058	no	263.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

149 targeting STAG1, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Literature-anchored findings (GeneRIF, showing 24)

• STAG1, a novel transcriptional target for p53, mediates p53-dependent apoptosis, and might be a good candidate for next-generation gene therapy in cancer. (PMID:15361841)
• STAG1 (Scc3/SA1) subunit of cohesin interacts with the CCTC-binding factor CTCF bound to the c-myc insulator element. (PMID:18550811)
• cohesin(SA1) and cohesin(SA2) are differentially required for telomere and centromere cohesion, respectively. (PMID:19822671)
• Nuclear import and export signals of human cohesins SA1/STAG1 and SA2/STAG2 expressed in Saccharomyces cerevisiae. (PMID:22715410)
• Rad21 binds to SA proteins through two SA-binding motifs on Rad21. (PMID:23874961)
• cohesin-SA1 and cohesin-SA2 participate in the DNA damage response (PMID:24324008)
• Mutations in STAG1 is associated with acute myeloid leukemia. (PMID:24335498)
• Data support the hypothesis that CTCF and cohesin SA-1 have multiple roles in the regulation of gene expression during erythropoiesis. (PMID:27219007)
• TRF1 tethers SA1 within telomeric regions that SA1 transiently interacts with. SA1 and TRF1 together form longer DNA-DNA pairing tracts than with TRF1 alone, as revealed by atomic force microscopy imaging (PMID:27298259)
• There is LOH at STAG1 and STAG2 loci in oral squamous cell carcinoma (OSCC), but OSCC and NM showed similar transcriptional levels of STAG1, STAG2, and PDS5B. (PMID:27341316)
• This first series reporting the phenotype ascribed to mutation in STAG1 highlights the importance of data sharing in the field of rare disorders. (PMID:28119487)
• Data indicate that cohesin subunit SA-1 (STAG1) is a promising therapeutic target in cancers with inactivating alterations of cohesin subunit SA-2 (STAG2). (PMID:28430577)
• Here the authors demonstrate that the most frequently mutated subunit of the cohesin complex, STAG2, displays a strong synthetic lethal interaction with its paralog STAG1. Mechanistically, STAG1 loss abrogates sister chromatid cohesion in STAG2 mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis. (PMID:28691904)
• The SNP but not wild-type had profound alterations in SA-1 expression with miR-29b inhibitor. (PMID:29471289)
• Study provides a comprehensive review of the function of STAG1/2 in human physiology and disease and an integrative analysis of available omics data on STAG alterations in a wide array of cancers, comprising 53 691 patients and 1067 cell lines. (PMID:31421907)
• Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation. (PMID:31495782)
• Specialized functions of cohesins STAG1 and STAG2 in 3D genome architecture. (PMID:32294612)
• STAG1 vulnerabilities for exploiting cohesin synthetic lethality in STAG2-deficient cancers. (PMID:32467316)
• PD-L1 regulates genomic stability via interaction with cohesin-SA1 in the nucleus. (PMID:33627620)
• Whole Exome Sequencing Identifies Cohesin Component STAG1 Mutation in de novo Acute Myeloid Leukemia (FAB M2): A Pilot Study with Cytogenetics, Clinical and Prognostic Implications. (PMID:33639073)
• STAG2 loss-of-function affects short-range genomic contacts and modulates the basal-luminal transcriptional program of bladder cancer cells. (PMID:34648034)
• Potential role of STAG1 mutations in genetic predisposition to childhood hematological malignancies. (PMID:35654786)
• Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2. (PMID:36898992)
• Single-molecule imaging reveals a direct role of CTCF’s zinc fingers in SA interaction and cluster-dependent RNA recruitment. (PMID:38742641)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	stag1a	ENSDARG00000061205
danio_rerio	stag1b	ENSDARG00000062137
mus_musculus	Stag1	ENSMUSG00000037286
rattus_norvegicus	Stag1	ENSRNOG00000015389
drosophila_melanogaster	SA2	FBGN0043865
caenorhabditis_elegans		WBGENE00004738

Paralogs (2): STAG3 (ENSG00000066923), STAG2 (ENSG00000101972)

Protein

Protein identifiers

Cohesin subunit SA-1 — Q8WVM7 (reviewed: Q8WVM7)

Alternative names: SCC3 homolog 1, Stromal antigen 1

All UniProt accessions (6): C9JJQ0, Q8WVM7, F8WCB3, F8WF82, H7C595, Q68DW7

UniProt curated annotations — full annotation on UniProt →

Function. Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis.

Subunit / interactions. Cohesin complexes are composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein (STAG1, STAG2 or STAG3). In cohesin complexes, STAG1 is mutually exclusive with STAG2 and STAG3. Interacts directly with RAD21 in cohesin complex. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1.

Subcellular location. Nucleus. Chromosome. Centromere.

Post-translational modifications. Phosphorylated by PLK1. The large dissociation of cohesin from chromosome arms during prophase is partly due to its phosphorylation.

Disease relevance. Intellectual developmental disorder, autosomal dominant 47 (MRD47) [MIM:617635] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD47 patients manifest developmental delay and mild to moderate intellectual disability, usually with delayed speech. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SCC3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WVM7-1	1	yes
Q8WVM7-2	2

RefSeq proteins (1): NP_005853* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013721	STAG	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR020839	SCD	Domain
IPR039662	Cohesin_Scc3/SA	Family
IPR056396	HEAT_SCC3-SA	Domain

Pfam: PF08514, PF21581, PF24571

UniProt features (88 total): helix 46, sequence variant 11, turn 8, modified residue 5, compositionally biased region 5, strand 4, region of interest 3, sequence conflict 2, chain 1, domain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
6QB5	X-RAY DIFFRACTION	2.02
6R7O	X-RAY DIFFRACTION	2.31
5QSX	X-RAY DIFFRACTION	2.34
6RRC	X-RAY DIFFRACTION	2.37
5QSY	X-RAY DIFFRACTION	2.4
5QSQ	X-RAY DIFFRACTION	2.48
5QST	X-RAY DIFFRACTION	2.58
5QSN	X-RAY DIFFRACTION	2.66
5QSO	X-RAY DIFFRACTION	2.7
5QSU	X-RAY DIFFRACTION	2.73
5QSM	X-RAY DIFFRACTION	2.74
5QSV	X-RAY DIFFRACTION	2.76
5QSP	X-RAY DIFFRACTION	2.89
5QSW	X-RAY DIFFRACTION	3.03
5QSS	X-RAY DIFFRACTION	3.08
5QSZ	X-RAY DIFFRACTION	3.08
6RRK	X-RAY DIFFRACTION	3.17
5QSR	X-RAY DIFFRACTION	3.28
6WG3	ELECTRON MICROSCOPY	5.3
7W1M	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVM7-F1	79.00	0.62

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 (6): 24, 756, 1062, 1065, 1093, 1161

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2468052	Establishment of Sister Chromatid Cohesion
R-HSA-2470946	Cohesin Loading onto Chromatin
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-68877	Mitotic Prometaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68884	Mitotic Telophase/Cytokinesis
R-HSA-68886	M Phase
R-HSA-69242	S Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 412 (showing top): E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, E2F_Q4_01, RRAGTTGT_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, E2F4DP1_01, REACTOME_MEIOTIC_SYNAPSIS, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, GGCNKCCATNK_UNKNOWN, MORF_RAD51L3

GO Biological Process (5): sister chromatid cohesion (GO:0007062), establishment of mitotic sister chromatid cohesion (GO:0034087), cell division (GO:0051301), mitotic spindle assembly (GO:0090307), chromosome segregation (GO:0007059)

GO Molecular Function (2): chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (12): chromosome, centromeric region (GO:0000775), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), cilium (GO:0005929), cohesin complex (GO:0008278), nuclear matrix (GO:0016363), nuclear body (GO:0016604), mitotic cohesin complex (GO:0030892), mitotic spindle pole (GO:0097431)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
M Phase	3
Meiosis	1
Mitotic Anaphase	1
S Phase	1
Mitotic Telophase/Cytokinesis	1
Mitotic Prometaphase	1
SUMO E3 ligases SUMOylate target proteins	1
ESR-mediated signaling	1
Reproduction	1
Cell Cycle	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell cycle process	2
binding	2
chromosome	2
nuclear lumen	2
intracellular membraneless organelle	2
chromosome organization	1
mitotic cell cycle	1
mitotic sister chromatid cohesion	1
establishment of sister chromatid cohesion	1
mitotic cell cycle process	1
cellular process	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
chromosomal region	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
protein-containing complex	1
nucleoplasm	1
cohesin complex	1
spindle pole	1
mitotic spindle	1

Protein interactions and networks

STRING

1756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAG1	RAD21	O60216	999
STAG1	PDS5A	Q29RF7	999
STAG1	SMC3	Q9UQE7	999
STAG1	SMC1A	Q14683	996
STAG1	WAPL	Q7Z5K2	983
STAG1	REC8	O95072	946
STAG1	ESPL1	Q14674	896
STAG1	ESCO1	Q5FWF5	895
STAG1	SMC1B	Q8NDV3	875
STAG1	NIPBL	Q6KC79	840
STAG1	MAU2	Q9Y6X3	823
STAG1	MDC1	Q14676	811
STAG1	CDCA5	Q96FF9	796
STAG1	STAG2	Q8N3U4	781
STAG1	ESCO2	Q56NI9	758

IntAct

92 interactions, top by confidence:

A	B	Type	Score
STAG2	RAD21	psi-mi:“MI:0914”(association)	0.970
SMC3	RAD21	psi-mi:“MI:0914”(association)	0.960
SMC3	RAD21	psi-mi:“MI:0915”(physical association)	0.960
STAG1	SMC3	psi-mi:“MI:0915”(physical association)	0.940
SMC3	STAG1	psi-mi:“MI:0915”(physical association)	0.940
STAG1	RAD21	psi-mi:“MI:0914”(association)	0.930
RAD21	SMC1A	psi-mi:“MI:0914”(association)	0.930
SMC1A	RAD21	psi-mi:“MI:0915”(physical association)	0.930
STAG1	RAD21	psi-mi:“MI:0915”(physical association)	0.930
WAPL	STAG2	psi-mi:“MI:0914”(association)	0.920
WAPL	RAD21	psi-mi:“MI:0915”(physical association)	0.910
RAD21	WAPL	psi-mi:“MI:0915”(physical association)	0.910
PDS5B	RAD21	psi-mi:“MI:0914”(association)	0.860
PDS5A	RAD21	psi-mi:“MI:0914”(association)	0.860
SMC3	WAPL	psi-mi:“MI:0914”(association)	0.820
STAG1	STAG2	psi-mi:“MI:0915”(physical association)	0.800
PDS5B	STAG1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (210): STAG1 (Affinity Capture-MS), STAG1 (Affinity Capture-MS), STAG1 (Affinity Capture-MS), STAG1 (Affinity Capture-MS), STAG1 (Affinity Capture-MS), EXOSC9 (Co-fractionation), RAD21 (Co-fractionation), SMC1A (Co-fractionation), SMC1B (Co-fractionation), STAG1 (Co-fractionation), STAG1 (Co-fractionation), STAG1 (Affinity Capture-Western), WAPAL (Affinity Capture-MS), STAG1 (Affinity Capture-MS), STAG1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3P7X4, A7S641, A8WG88, A9ULY7, B0R034, B0W6N3, B5DFC8, B5ME19, D6WIX5, E7EXT2, F7AEX0, O60308, O95202, P0C204, P45433, P53569, Q03701, Q0VA06, Q173M7, Q1L987, Q28HX4, Q3SYW6, Q3ZC50, Q4QR58, Q5RAT8, Q5RCI4, Q5U2X6, Q5XGZ8, Q5XIN6, Q5ZK33, Q66I12, Q6AZI2, Q6IVW0, Q6P1V4, Q6PFQ2, Q6PGY6, Q7PGE8, Q7SYB2, Q8BZN6, Q8R1B4

Diamond homologs: O35638, O70576, P0CL83, P0CL84, P0CL85, Q19555, Q8N3U4, Q8TBR4, Q8WVM7, Q99M76, Q9D3E6, Q9DGN0, Q9DGN1, Q9UJ98, O13816, O82265

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STAG1	“form complex”	“Cohesin complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Meiosis	5	31.7×	3e-05
Meiotic synapsis	7	21.9×	2e-06
Reproduction	5	21.1×	2e-04
SUMO E3 ligases SUMOylate target proteins	5	19.8×	2e-04
SUMOylation	5	18.1×	3e-04
Resolution of Sister Chromatid Cohesion	9	17.3×	2e-07
SUMOylation of DNA damage response and repair proteins	5	16.3×	5e-04
Separation of Sister Chromatids	9	12.2×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitotic sister chromatid cohesion	5	90.6×	1e-06
cell division	11	8.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	33
Uncertain significance	303
Likely benign	237
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2124580	NM_005862.3(STAG1):c.2116del (p.Asp706fs)	Pathogenic
2572950	NM_005862.3(STAG1):c.3046C>T (p.Arg1016Ter)	Pathogenic
3027404	GRCh37/hg19 3q22.3(chr3:136219065-136365036)x1	Pathogenic
3323043	NM_005862.3(STAG1):c.1010G>A (p.Trp337Ter)	Pathogenic
3650660	NM_005862.3(STAG1):c.282dup (p.Lys95fs)	Pathogenic
3769899	NM_005862.3(STAG1):c.2911C>T (p.Arg971Ter)	Pathogenic
3772689	NM_005862.3(STAG1):c.395-2A>T	Pathogenic
3802102	NM_005862.3(STAG1):c.1339del (p.Ala447fs)	Pathogenic
4176067	NM_005862.3(STAG1):c.2964C>A (p.Tyr988Ter)	Pathogenic
437896	NC_000003.11:g.136254742_136427833del	Pathogenic
451354	NM_005862.3(STAG1):c.469G>A (p.Glu157Lys)	Pathogenic
4528293	NM_005862.3(STAG1):c.1141dup (p.Met381fs)	Pathogenic
4537876	NM_005862.3(STAG1):c.3616C>T (p.Arg1206Ter)	Pathogenic
4809952	NM_005862.3(STAG1):c.455_458del (p.Thr152fs)	Pathogenic
545081	NM_005862.3(STAG1):c.2241G>A (p.Trp747Ter)	Pathogenic
686586	GRCh37/hg19 3q22.3(chr3:136192663-136396078)x1	Pathogenic
689317	GRCh37/hg19 3q22.3(chr3:136193031-136305476)x1	Pathogenic
802013	NM_005862.3(STAG1):c.260del (p.Leu87fs)	Pathogenic
830788	NC_000003.12:g.(?136452033)(136477412_?)del	Pathogenic
995415	NM_005862.3(STAG1):c.391C>T (p.Arg131Ter)	Pathogenic
1013230	NM_005862.3(STAG1):c.997A>G (p.Lys333Glu)	Likely pathogenic
1064844	NM_005862.3(STAG1):c.132+5G>A	Likely pathogenic
1064852	NM_005862.3(STAG1):c.964_965insCT (p.Tyr322fs)	Likely pathogenic
1325144	NM_005862.3(STAG1):c.513del (p.Gln170_Trp171insTer)	Likely pathogenic
1333942	NM_005862.3(STAG1):c.625G>C (p.Gly209Arg)	Likely pathogenic
1700129	NM_005862.3(STAG1):c.947del (p.Gly316fs)	Likely pathogenic
1709088	NM_005862.3(STAG1):c.3691C>T (p.Arg1231Ter)	Likely pathogenic
1709726	NM_005862.3(STAG1):c.1716dup (p.Ile573fs)	Likely pathogenic
1711580	NM_005862.3(STAG1):c.3488A>G (p.Glu1163Gly)	Likely pathogenic
2036530	NM_005862.3(STAG1):c.1546+1G>T	Likely pathogenic

SpliceAI

6933 predictions. Top by Δscore:

Variant	Effect	Δscore
3:136338368:A:AC	donor_gain	1.0000
3:136338369:C:CC	donor_gain	1.0000
3:136338449:GG:G	acceptor_gain	1.0000
3:136338451:C:CC	acceptor_gain	1.0000
3:136338451:C:G	acceptor_loss	1.0000
3:136340486:TCTA:T	donor_loss	1.0000
3:136340487:CTAC:C	donor_loss	1.0000
3:136340490:C:CT	donor_loss	1.0000
3:136340510:T:TA	donor_gain	1.0000
3:136340601:CCCGA:C	acceptor_gain	1.0000
3:136340602:CCGA:C	acceptor_gain	1.0000
3:136340602:CCGAC:C	acceptor_gain	1.0000
3:136340603:CGA:C	acceptor_gain	1.0000
3:136340603:CGAC:C	acceptor_gain	1.0000
3:136340604:GA:G	acceptor_gain	1.0000
3:136340604:GAC:G	acceptor_loss	1.0000
3:136340606:C:A	acceptor_loss	1.0000
3:136340606:C:CC	acceptor_gain	1.0000
3:136341439:A:AC	donor_gain	1.0000
3:136341440:C:CC	donor_gain	1.0000
3:136341440:CA:C	donor_gain	1.0000
3:136341440:CACAG:C	donor_gain	1.0000
3:136341465:A:AC	donor_gain	1.0000
3:136341466:C:CC	donor_gain	1.0000
3:136343827:CTT:C	donor_loss	1.0000
3:136343828:TTA:T	donor_loss	1.0000
3:136343829:TACT:T	donor_loss	1.0000
3:136343830:A:AC	donor_gain	1.0000
3:136343830:AC:A	donor_loss	1.0000
3:136343831:C:CT	donor_gain	1.0000

AlphaMissense

8388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:136349274:A:G	L1052S	1.000
3:136349278:A:G	S1051P	1.000
3:136349287:A:C	Y1048D	1.000
3:136349287:A:G	Y1048H	1.000
3:136349287:A:T	Y1048N	1.000
3:136349295:A:G	L1045P	1.000
3:136349298:G:C	P1044R	1.000
3:136349305:A:G	W1042R	1.000
3:136349305:A:T	W1042R	1.000
3:136349352:A:G	L1026P	1.000
3:136357720:A:T	V1022D	1.000
3:136357728:T:A	K1019N	1.000
3:136357728:T:G	K1019N	1.000
3:136357730:T:C	K1019E	1.000
3:136357732:T:A	D1018V	1.000
3:136357732:T:C	D1018G	1.000
3:136357732:T:G	D1018A	1.000
3:136357733:C:A	D1018Y	1.000
3:136357733:C:G	D1018H	1.000
3:136357744:A:C	L1014R	1.000
3:136357744:A:G	L1014P	1.000
3:136357744:A:T	L1014H	1.000
3:136357745:G:A	L1014F	1.000
3:136357746:T:A	K1013N	1.000
3:136357746:T:G	K1013N	1.000
3:136357748:T:C	K1013E	1.000
3:136357753:G:A	S1011F	1.000
3:136357753:G:T	S1011Y	1.000
3:136357755:A:C	F1010L	1.000
3:136357755:A:T	F1010L	1.000

dbSNP variants (sampled 300 via entrez): RS1000011025 (3:136751701 G>A), RS1000017719 (3:136458141 T>C), RS1000022039 (3:136703826 A>C,G,T), RS1000025632 (3:136440656 A>G), RS1000028028 (3:136663702 A>G), RS1000032833 (3:136475975 C>T), RS1000056674 (3:136440987 G>C), RS1000069506 (3:136655482 G>C,T), RS1000070493 (3:136551140 G>C), RS1000075772 (3:136531368 T>C), RS1000091593 (3:136383737 CGA>C), RS1000093878 (3:136393429 C>T), RS1000100731 (3:136616306 T>C), RS1000104173 (3:136342542 C>G,T), RS1000109072 (3:136499578 A>G)

Disease associations

OMIM: gene MIM:604358 | disease phenotypes: MIM:617635

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 47	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (5): intellectual disability, autosomal dominant 47 (MONDO:0030912), neurodevelopmental disorder (MONDO:0700092), coloboma (MONDO:0001476), intellectual disability (MONDO:0001071), premature menopause (MONDO:0001119)

Orphanet (3): STAG1-related intellectual disability-facial dysmorphism-gastroesophageal reflux syndrome (Orphanet:502434), OBSOLETE: Ocular coloboma (Orphanet:194), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	5
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	5
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
trichostatin A	decreases expression, increases expression	2
Cisplatin	affects expression, decreases expression, increases reaction	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
afimoxifene	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
jinfukang	decreases expression, increases reaction	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6T9	SEES3-1V human STAG1, clone1	Embryonic stem cell	Male
CVCL_A6U0	SEES3-1V human STAG1, clone2	Embryonic stem cell	Male
CVCL_A6U1	SEES3-1V human STAG1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice