Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth. Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth. In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons

OMIMResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
Pubs (1 yr)
P/LP submissions
P/LP missense
0.46
LOEUF
DN
Mechanism· predicted
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.46LOEUF
pLI 0.039
Z-score 4.12
OE 0.27 (0.170.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.14Z-score
OE missense 0.66 (0.590.74)
209 obs / 316.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.27 (0.170.46)
00.351.4
Missense OE?0.66 (0.590.74)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 10 / 37.0Missense obs/exp: 209 / 316.0Syn Z: 0.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SHTN1 · 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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