STAT2

signal transducer and activator of transcription 2, the group of SH2 domain containing

Basic information

Region (hg38): 12:56341597-56360203

Links

ENSG00000170581 ∙ NCBI:6773 ∙ OMIM:600556 ∙ HGNC:11363 ∙ Uniprot:P52630 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (Supportive), mode of inheritance: AR
• primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (Strong), mode of inheritance: AR
• pseudo-TORCH syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 44; Pseudo-TORCH syndrome 3	AR	Allergy/Immunology/Infectious	Individuals with both conditions can demonstrate infection susceptibility, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; In Immunodeficiency 44, adverse reactions to vaccinations have been reported, and awareness may help prevent morbidity; In Pseudo-Torch syndrome 3, the use of immunologic medical treatments (eg, dexamethasone, ruxolitinib) has been described as showing some benefit; HSCT has been described in Pseudo-Torch syndrome 3	Allergy/Immunology/Infectious; Biochemical; Renal	23391734; 26122121; 31836668; 32092142

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAT2 gene.

• Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (21 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAT2 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	97	2	100
missense	1		185	1	6	193
nonsense	9					9
start loss						0
frameshift	12					12
inframe indel			6			6
splice donor/acceptor (+/-2bp)	1	3				4
splice region			12	26	2	40
non coding			1	77	3	81
Total	23	3	193	175	11

Highest pathogenic variant AF is 0.0000131

Variants in STAT2

This is a list of pathogenic ClinVar variants found in the STAT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-56343402-G-A		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Dec 09, 2021)
12-56343406-T-C		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Aug 23, 2022)
12-56343408-A-C		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Feb 18, 2022)
12-56343409-A-G		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection • STAT2-related disorder	Likely benign (Nov 07, 2023)
12-56343412-G-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Aug 03, 2021)
12-56343420-G-C		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Aug 08, 2022)
12-56343420-G-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Aug 24, 2021)
12-56343438-C-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Aug 15, 2018)
12-56343439-G-A		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Jun 04, 2022)
12-56343443-G-C		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Likely benign (Mar 13, 2023)
12-56343445-C-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 19, 2023)
12-56343452-C-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Likely benign (Jul 18, 2023)
12-56343454-C-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Aug 24, 2021)
12-56343460-C-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (May 18, 2023)
12-56343467-C-A		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection • STAT2-related disorder	Benign/Likely benign (Aug 01, 2024)
12-56343471-C-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Oct 25, 2022)
12-56343472-C-A		not specified	Benign (Mar 29, 2016)
12-56343472-CA-AG		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Benign (Jan 31, 2024)
12-56343473-A-G		not specified • Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Benign (Dec 11, 2023)
12-56343494-C-T		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Likely benign (Dec 11, 2023)
12-56343495-G-A		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Apr 26, 2023)
12-56343499-T-G		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Uncertain significance (Aug 17, 2022)
12-56343500-G-A		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Likely benign (Aug 27, 2023)
12-56343535-G-A		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Likely benign (Nov 10, 2022)
12-56343811-A-G		Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection	Likely benign (Dec 24, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAT2	protein_coding	protein_coding	ENST00000314128	23	18559

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.931	0.0694	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.60	299	455	0.658	0.0000248	5528
Missense in Polyphen		87	153.2	0.56788		1966
Synonymous	1.30	160	182	0.877	0.00000936	1658
Loss of Function	5.65	11	57.0	0.193	0.00000310	593

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000246	0.000246
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000277	0.000277
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Signal transducer and activator of transcription that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state (PubMed:9020188, PubMed:23391734). Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively (PubMed:26122121). {ECO:0000269|PubMed:23391734, ECO:0000269|PubMed:26122121, ECO:0000269|PubMed:9020188}.
• Disease: DISEASE: Immunodeficiency 44 (IMD44) [MIM:616636]: An autosomal recessive disorder characterized by increased susceptibility to viral infection, resulting in some patients in encephalopathy and infection-associated neurologic decompensation. {ECO:0000269|PubMed:23391734, ECO:0000269|PubMed:26122121}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Influenza A - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);JAK-STAT-Core;Type III interferon signaling;Adipogenesis;Chemokine signaling pathway;The human immune response to tuberculosis;Interferon type I signaling pathways;Type II interferon signaling (IFNG);ifn alpha signaling pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Immune System;IFN alpha signaling;EGFR1;CXCR4-mediated signaling events;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;Regulation of IFNA signaling;Interferon alpha/beta signaling;IL27-mediated signaling events;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.357

Intolerance Scores

• loftool: 0.154
• rvis_EVS: -0.73
• rvis_percentile_EVS: 14.14

Haploinsufficiency Scores

• pHI: 0.524
• hipred: Y
• hipred_score: 0.568
• ghis: 0.587

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stat2
• Phenotype: 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; immune system phenotype

Gene ontology

• Biological process: regulation of protein phosphorylation;regulation of transcription by RNA polymerase II;JAK-STAT cascade;viral process;cytokine-mediated signaling pathway;defense response to virus;type I interferon signaling pathway;regulation of mitochondrial fission
• Cellular component: nucleoplasm;cytosol;plasma membrane
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;identical protein binding;ubiquitin-like protein ligase binding