SLIT3

Chr 5

slit guidance ligand 3

Also known as: MEGF5, SLIL2, SLIT1, Slit-3, slit2

NCBI Gene: 6586ENSG00000184347UniProt: O75094OMIM: 603745

The SLIT3 protein is secreted and acts as a molecular guidance cue in cellular migration through interaction with roundabout homolog receptors. Mutations cause autosomal dominant congenital heart disease and autosomal recessive intellectual developmental disorder with cardiac arrhythmia. The gene is highly constrained against loss-of-function variants (LOEUF 0.318), indicating intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.32
Clinical Summary— SLIT3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 239 VUS of 347 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.752
Z-score 6.67
OE 0.21 (0.15–0.32)
Highly constrained

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

Missense Constraint
1.94Z-score
OE missense 0.82 (0.77–0.87)
742 obs / 906.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.15–0.32)
0≤0.351.4
Missense OE0.82 (0.77–0.87)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 18 / 83.9Missense obs/exp: 742 / 906.7Syn Z: -0.18

ClinVar Variant Classifications

347 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic2
VUS239
Likely Benign44
Benign14
16
Pathogenic
2
Likely Pathogenic
239
VUS
44
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
1
1
0
2
VUS
2
231
6
0
239
Likely Benign
0
11
1
32
44
Benign
0
4
4
6
14
Total22472838315

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

View in ClinVar →

Protein Context — Lollipop Plot

SLIT3 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SLIT3: a novel regulator of odontogenic differentiation through Akt/GSK3β/β-catenin signaling pathway.
Jiang L et al.·Int J Oral Sci
2026Open Access
Elevated serum Slit3 independently predicts disease activity and interstitial lung disease in rheumatoid arthritis.
Zhang X et al.·Clinics (Sao Paulo)
2026Open Access
SLIT3 fragments orchestrate neurovascular expansion and thermogenesis in brown adipose tissue.
Serdan TDA et al.·Nat Commun
2026Open Access
SLIT3/ROBO1 axis contributes to angiogenic-osteogenic coupling in endothelial progenitor cells and peripheral blood mesenchymal stem cells.
Rong Q et al.·Stem Cell Res Ther
2026Open Access
PTH induced osteoblast Slit3 to decrease aberrant sensory innervation in degenerated vertebral endplates to relieve low back pain in mice.
Zhang W et al.·Bone Res
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients