STAT5A

Chr 17

signal transducer and activator of transcription 5A

Also known as: MGF, STAT5

STAT5A encodes a transcription factor that mediates cellular responses to cytokines and growth factors including interleukins, growth hormone, and erythropoietin by translocating to the nucleus upon phosphorylation and activating target gene transcription. Pathogenic variants cause autosomal recessive growth hormone insensitivity syndrome, resulting in severe growth failure and immune dysfunction. The mechanism involves loss of STAT5A-mediated transcriptional activation downstream of growth hormone and cytokine receptors.

Summary from RefSeq, UniProt
0
Active trials
63
Pubs (1 yr)
6
P/LP submissions
0%
P/LP missense
0.20
LOEUF· LoF intol.
Mechanism
Clinical SummarySTAT5A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 68 VUS of 97 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 5.69
OE 0.09 (0.040.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.94Z-score
OE missense 0.62 (0.560.68)
294 obs / 474.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.040.20)
00.351.4
Missense OE0.62 (0.560.68)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 4 / 45.4Missense obs/exp: 294 / 474.1Syn Z: 1.16

ClinVar Variant Classifications

97 submitted variants in ClinVar

Classification Summary

Pathogenic6
VUS68
Likely Benign3
Benign6
6
Pathogenic
68
VUS
3
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
1
66
1
0
68
Likely Benign
0
3
0
0
3
Benign
0
1
1
4
6
Total1708483

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STAT5A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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