STAG1

stromal antigen 1, the group of Armadillo like helical domain containing|Cohesin complex

Basic information

Region (hg38): 3:136336235-136752403

Links

ENSG00000118007 ∙ NCBI:10274 ∙ OMIM:604358 ∙ HGNC:11354 ∙ Uniprot:Q8WVM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 47 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 47 (Moderate), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 47	AD	General	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	Craniofacial; Neurologic	28119487

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAG1 gene.

• not provided (211 variants)
• Intellectual disability, autosomal dominant 47 (50 variants)
• Inborn genetic diseases (29 variants)
• STAG1-related disorder (6 variants)
• not specified (4 variants)
• STAG1-related condition (3 variants)
• Neurodevelopmental disorder (2 variants)
• Global developmental delay (1 variants)
• Intellectual disability (1 variants)
• STAG1-Related Disorders (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	41	8	50
missense	1	10	105	14	6	136
nonsense	2	5				7
start loss						0
frameshift	2	8	1			11
inframe indel			2			2
splice donor/acceptor (+/-2bp)		3				3
splice region		1	8	10	7	26
non coding			4	30	13	47
Total	5	26	113	85	27

Highest pathogenic variant AF is 0.00000657

Variants in STAG1

This is a list of pathogenic ClinVar variants found in the STAG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-136338270-C-G			Uncertain significance (Dec 13, 2023)
3-136338358-T-C			Likely benign (Aug 04, 2023)
3-136338362-A-C			Uncertain significance (Feb 14, 2023)
3-136338363-C-T			Likely benign (Nov 08, 2022)
3-136338372-A-T			Uncertain significance (Nov 02, 2022)
3-136338372-AA-TT			Uncertain significance (Mar 08, 2023)
3-136338397-G-A			Likely benign (Oct 03, 2023)
3-136338422-GCTCT-G			Likely pathogenic (Dec 06, 2018)
3-136338431-C-T			Uncertain significance (May 31, 2023)
3-136338432-G-A		Intellectual disability, autosomal dominant 47	Likely pathogenic (Jan 14, 2022)
3-136338467-G-GTTTC			Likely benign (Aug 10, 2023)
3-136340475-T-C			Likely benign (Dec 27, 2023)
3-136340479-GAATTTCTC-G			Benign/Likely benign (Sep 10, 2023)
3-136340493-G-A			Likely benign (Jun 01, 2022)
3-136340528-A-G			Uncertain significance (Nov 08, 2023)
3-136340582-G-A		Intellectual disability, autosomal dominant 47	Uncertain significance (Aug 04, 2023)
3-136340599-A-G			Likely benign (Nov 13, 2022)
3-136340600-C-G		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
3-136340600-C-T		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
3-136340604-G-A			Likely pathogenic (Oct 23, 2020)
3-136340619-G-A			Benign (Jan 26, 2024)
3-136341452-C-T			Likely benign (Jan 07, 2024)
3-136341454-C-T		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
3-136341462-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 13, 2023)
3-136341472-T-C			Uncertain significance (May 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAG1	protein_coding	protein_coding	ENST00000383202	33	416144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.49e-10	125726	0	5	125731	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.44	338	659	0.513	0.0000334	8363
Missense in Polyphen		37	177.12	0.2089		2368
Synonymous	-0.894	239	222	1.08	0.0000110	2247
Loss of Function	7.69	4	76.7	0.0521	0.00000429	919

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000222	0.000198
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000894	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Mental retardation, autosomal dominant 47 (MRD47) [MIM:617635]: A form of mental retardation, 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. {ECO:0000269|PubMed:28119487}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);Regulation of sister chromatid separation at the metaphase-anaphase transition;Signal Transduction;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Reproduction;SUMOylation;Establishment of Sister Chromatid Cohesion;S Phase;Meiotic synapsis;Meiosis;Signaling by Nuclear Receptors;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Cohesin Loading onto Chromatin;Mitotic Telophase/Cytokinesis;M Phase;Estrogen-dependent gene expression;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;ESR-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.214
• rvis_EVS: -1.04
• rvis_percentile_EVS: 7.71

Haploinsufficiency Scores

• pHI: 0.842
• hipred: Y
• hipred_score: 0.739
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.934

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Stag1
• Phenotype: neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; renal/urinary system phenotype; skeleton phenotype; craniofacial phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cell cycle;chromosome segregation;sister chromatid cohesion;positive regulation of transcription by RNA polymerase II;cell division;regulation of mitotic spindle assembly
• Cellular component: chromosome, centromeric region;chromatin;nucleus;nucleoplasm;chromosome;cytosol;cohesin complex;nuclear matrix;nuclear body;mitotic spindle pole
• Molecular function: DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;protein binding