STAT5A

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for tumorigenesis. The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

Previous symbols:

STAT5

MANE transcript

NM_001288718.2

Inheritance

—

ClinVar variants

U:76B:8

Top phenotype

Pyloric stenosis

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr17:42,287,547-42,311,943

External References & Databases

Ensembl (ENSG00000126561)

Transcript & Mutation Effects

hg38 • Region Span ~24.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STAT5A variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 10

Pyloric stenosisTotal: 1

Esophageal atresiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001288718.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		4 clinvar	5
missense			70 clinvar	3 clinvar	1 clinvar	74
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	76	3	5	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001288718.2	RefSeq	NP_001275647.1	18	MANE Select
ENST00000590949.6	Ensembl	ENSP00000468749.1	18	MANE Select
NM_001288719.2	RefSeq	NP_001275648.1	17	Standard
NM_001288720.2	RefSeq	NP_001275649.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
stat5a	Danio rerio	Structure: nucleate erythrocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

stat5a

Danio rerio

Structure: nucleate erythrocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

positive regulation of endothelial cell proliferation
regulation of transcription by RNA polymerase II
JAK-STAT cascade
lactation
peptidyl-tyrosine phosphorylation

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity
protein tyrosine kinase activity
protein binding

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000345506
Coding exons: 18
Length: 24397
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125747
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.94	294	474	0.620	0.0000299	5220
Missense (PolyPhen)		74	145.29	0.50931		1581
Synonymous	1.16	181	202	0.896	0.0000131	1527
Loss of Function	5.69	4	45.4	0.0882	0.00000222	475

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation. {ECO:0000269|PubMed:15534001}.;

Recessive Scores

pRec: 0.590

Intolerance Scores

LoFtool: 0.182
RVIS EVS: -0.64
RVIS percentile EVS: 16.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.964

Gene Damage Prediction

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