SLIT2

Chr 4

slit guidance ligand 2

Also known as: SLIL3, Slit-2

This gene encodes SLIT2, a secreted glycoprotein that functions as a molecular guidance cue for axonal navigation and neuronal migration during brain and spinal cord development, particularly at the ventral midline. Mutations cause autosomal dominant congenital diaphragmatic hernia and other developmental anomalies. The gene is highly constrained against loss-of-function variants, indicating mutations are likely to have significant clinical consequences.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.16
Clinical SummarySLIT2
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
9 unique Pathogenic / Likely Pathogenic· 241 VUS of 400 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 7.68
OE 0.09 (0.050.16)
Highly constrained

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

Missense Constraint
2.10Z-score
OE missense 0.80 (0.750.85)
687 obs / 860.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.050.16)
00.351.4
Missense OE0.80 (0.750.85)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 7 / 82.1Missense obs/exp: 687 / 860.3Syn Z: -0.29

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS241
Likely Benign119
Benign6
Conflicting3
8
Pathogenic
1
Likely Pathogenic
241
VUS
119
Likely Benign
6
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
233
5
3
241
Likely Benign
0
2
46
71
119
Benign
0
0
5
1
6
Conflicting
3
Total02356575378

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

View in ClinVar →

Protein Context — Lollipop Plot

SLIT2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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