STAT5B

signal transducer and activator of transcription 5B, the group of SH2 domain containing

Basic information

Region (hg38): 17:42199175-42288633

Links

ENSG00000173757 ∙ NCBI:6777 ∙ OMIM:604260 ∙ HGNC:11367 ∙ Uniprot:P51692 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• growth hormone insensitivity with immune dysregulation 1, autosomal recessive (Strong), mode of inheritance: AR
• growth hormone insensitivity with immune dysregulation 1, autosomal recessive (Supportive), mode of inheritance: AR
• growth hormone insensitivity with immune dysregulation 1, autosomal recessive (Moderate), mode of inheritance: AR
• growth hormone insensitivity syndrome with immune dysregulation (Definitive), mode of inheritance: Semidominant
• growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant (Strong), mode of inheritance: AD
• growth hormone insensitivity with immune dysregulation 1, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant; Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	AD/AR	Allergy/Immunology/Infectious; Endocrine	In Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant, medical management (eg, with growth or hormone or recombinant human IGF-1) might be effective, though this remains to be fully evaluated; Individuals with Growth hormone insensitivity with immune dysregulation 1, autosomal recessive demonstrate infection susceptibility, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; As relates to growth deficiency in Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, medical management (eg, with with recombinant human IGF-1) may be beneficial	Allergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal	8977385; 13679528; 15827093; 17030597; 16787985; 17389811; 21396575; 22423513; 22678306; 29844444

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAT5B gene.

• Growth hormone insensitivity with immune dysregulation 1, autosomal recessive (338 variants)
• not provided (41 variants)
• not specified (12 variants)
• Inborn genetic diseases (7 variants)
• Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant (6 variants)
• Growth hormone insensitivity with immune dysregulation 1, autosomal recessive;Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant (6 variants)
• Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant;Growth hormone insensitivity with immune dysregulation 1, autosomal recessive (2 variants)
• STAT5B-related condition (2 variants)
• STAT5B-related growth hormone insensitivity syndrome (1 variants)
• Growth hormone insensitivity syndrome with immune dysregulation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAT5B 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			5	113	6	124
missense		1	142	2	1	146
nonsense	7		1			8
start loss						0
frameshift	5					5
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			11	14		25
non coding			5	34	12	51
Total	12	2	153	149	19

Highest pathogenic variant AF is 0.00000659

Variants in STAT5B

This is a list of pathogenic ClinVar variants found in the STAT5B region.

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

Position	Type	Phenotype	Significance	ClinVar
17-42201524-GCA-G			Benign (Jun 19, 2021)
17-42201741-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Jul 20, 2023)
17-42201743-A-G		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive • Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant	Uncertain significance (Jul 29, 2020)
17-42201744-T-C		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Mar 30, 2023)
17-42201747-T-G		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (May 17, 2022)
17-42201749-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive;Growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant • Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Nov 25, 2023)
17-42201750-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Jan 29, 2024)
17-42201754-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Nov 18, 2019)
17-42201758-T-G		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Aug 10, 2023)
17-42201762-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Apr 07, 2023)
17-42201768-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Mar 09, 2023)
17-42201769-T-C		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Apr 10, 2023)
17-42201773-T-C		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Jan 23, 2024)
17-42201778-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Jul 19, 2022)
17-42201786-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Aug 27, 2023)
17-42201788-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Aug 04, 2023)
17-42201792-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Nov 27, 2023)
17-42201799-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Oct 14, 2023)
17-42201800-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Nov 28, 2023)
17-42201803-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (May 09, 2023)
17-42201805-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Jan 03, 2022)
17-42201809-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Mar 29, 2022)
17-42201810-G-A		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Likely benign (Jan 19, 2023)
17-42201827-G-C		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Oct 07, 2022)
17-42201830-C-T		Growth hormone insensitivity with immune dysregulation 1, autosomal recessive	Uncertain significance (Dec 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAT5B	protein_coding	protein_coding	ENST00000293328	18	77540

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000118	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.00	212	451	0.470	0.0000282	5188
Missense in Polyphen		52	127.19	0.40883		1473
Synonymous	0.984	172	189	0.909	0.0000126	1497
Loss of Function	5.73	5	47.8	0.105	0.00000251	495

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000161	0.000152
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000882	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription. Positively regulates hematopoietic/erythroid differentiation. {ECO:0000269|PubMed:20702587, ECO:0000269|PubMed:8732682}.
• Disease: DISEASE: Growth hormone insensitivity with immunodeficiency (GHII) [MIM:245590]: A disease characterized by short stature, growth hormone deficiency in the presence of normal to elevated circulating concentrations of growth hormone, resistance to hexogeneous growth hormone therapy, and recurrent infections. {ECO:0000269|PubMed:13679528, ECO:0000269|PubMed:15827093, ECO:0000269|PubMed:22419735}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Non-small cell lung cancer - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Necroptosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;JAK-STAT-Core;IL-5 Signaling Pathway;Leptin signaling pathway;Prolactin Signaling Pathway;IL-7 Signaling Pathway;IL-9 Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;White fat cell differentiation;AGE-RAGE pathway;Adipogenesis;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;JAK-STAT;IL-3 Signaling Pathway;Kit receptor signaling pathway;Rac1-Pak1-p38-MMP-2 pathway;IL-4 Signaling Pathway;Chemokine signaling pathway;PDGFR-beta pathway;White fat cell differentiation;EGF-EGFR Signaling Pathway;Endochondral Ossification;IL-2 Signaling Pathway;EPO Receptor Signaling;Interleukin-7 signaling;Disease;IL-3 signaling;Signal Transduction;Signaling by Interleukins;mechanism of gene regulation by peroxisome proliferators via ppara;inhibition of cellular proliferation by gleevec;bioactive peptide induced signaling pathway;il 2 signaling pathway;il-7 signal transduction;Growth hormone receptor signaling;il-2 receptor beta chain in t cell activation;il22 soluble receptor signaling pathway;Prolactin receptor signaling;Prolactin;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;Signaling by PDGF;Growth hormone signaling;il 3 signaling pathway;Oncostatin_M;Immune System;Interleukin-2 family signaling;IL5-mediated signaling events;KitReceptor;ErbB4 signaling events;IL-2 signaling;epo signaling pathway;IL-5 signaling;IL-7 signaling;tpo signaling pathway;EGFR1;growth hormone signaling pathway;Glucocorticoid receptor regulatory network;CXCR4-mediated signaling events;JAK STAT MolecularVariation 2;Signaling events mediated by TCPTP;JAK STAT pathway and regulation;PDGF;IL2;Signaling by Leptin;EPO signaling;IL3;IL2-mediated signaling events;Downstream signal transduction;Angiopoietin receptor Tie2-mediated signaling;Interleukin-2 signaling;IL4;EPO signaling pathway;Signaling by SCF-KIT;Signaling by FGFR in disease;IL5;IL6;IL-7;Signaling by cytosolic FGFR1 fusion mutants;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Signaling by Receptor Tyrosine Kinases;IL9;GMCSF-mediated signaling events;IL2 signaling events mediated by STAT5;Diseases of signal transduction;PDGFR-beta signaling pathway;IL4-mediated signaling events;Signaling events mediated by PTP1B;FGF signaling pathway;IL3-mediated signaling events;TSLP;Interleukin-3, 5 and GM-CSF signaling (Consensus)

Intolerance Scores

• loftool: 0.0917
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.3

Haploinsufficiency Scores

• pHI: 0.509
• hipred: Y
• hipred_score: 0.840
• ghis: 0.627

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stat5b
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; 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); homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system 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); normal phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; renal/urinary system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: stat5a
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: luteinization;natural killer cell differentiation;regulation of transcription by RNA polymerase II;JAK-STAT cascade;female pregnancy;lactation;peptidyl-tyrosine phosphorylation;regulation of steroid metabolic process;cytokine-mediated signaling pathway;taurine metabolic process;lipid storage;regulation of epithelial cell differentiation;response to estradiol;positive regulation of natural killer cell proliferation;positive regulation of natural killer cell differentiation;cellular response to hormone stimulus;T cell differentiation in thymus;interleukin-15-mediated signaling pathway;interleukin-2-mediated signaling pathway;interleukin-7-mediated signaling pathway;interleukin-9-mediated signaling pathway;regulation of multicellular organism growth;positive regulation of multicellular organism growth;positive regulation of activated T cell proliferation;progesterone metabolic process;T cell homeostasis;negative regulation of apoptotic process;positive regulation of interleukin-2 biosynthetic process;positive regulation of B cell differentiation;positive regulation of gamma-delta T cell differentiation;negative regulation of erythrocyte differentiation;positive regulation of erythrocyte differentiation;positive regulation of mitotic cell cycle;positive regulation of transcription by RNA polymerase II;positive regulation of natural killer cell mediated cytotoxicity;development of secondary female sexual characteristics;development of secondary male sexual characteristics;Peyer's patch development;positive regulation of inflammatory response;JAK-STAT cascade involved in growth hormone signaling pathway;response to interleukin-4;cellular response to growth factor stimulus;cellular response to epidermal growth factor stimulus;mast cell migration
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein tyrosine kinase activity;protein binding;glucocorticoid receptor binding;protein dimerization activity