SLIT3

protein-coding

slit guidance ligand 3, the group of MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is secreted, likely interacting with roundabout homolog receptors to effect cell migration. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

Previous symbols:

SLIL2

MANE transcript

NM_003062.4

Inheritance

ClinVar variants

P:1U:250B:49

Top phenotype

SLIT3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr5:168,661,740-169,301,139

External References & Databases

Ensembl (ENSG00000184347)

Transcript & Mutation Effects

hg38 • Region Span ~639.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital diaphragmatic herniaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005711

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLIT3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 229

not providedTotal: 46

SLIT3-related disorderTotal: 19

SLIT3-related anomalies of the kidney and urinary tractTotal: 5

Familial congenital diaphragmatic herniaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003062.4. 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			5 clinvar	32 clinvar	3 clinvar	40
missense		1 clinvar	238 clinvar	11 clinvar	3 clinvar	253
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	1	250	43	6	300

Highest pathogenic variant AF is 0.000010260802

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003062.4	RefSeq	NP_003053.2	36	MANE Select
ENST00000519560.6	Ensembl	ENSP00000430333.2	36	MANE Select
NM_001271946.2	RefSeq	NP_001258875.2	36	Standard
ENST00000332966.8	Ensembl	ENSP00000332164.8	36	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Spinal Cord Injury
Developmental Biology
Regulation of commissural axon pathfinding by SLIT and ROBO
Netrin-1 signaling

Biological Process

aortic valve morphogenesis
atrioventricular valve morphogenesis
axon guidance
negative regulation of cell population proliferation
negative regulation of gene expression

Molecular Function

calcium ion binding
Roundabout binding

Cellular Component

extracellular space
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000519560
Coding exons: 36
Length: 639389
Individuals with no LoFs: 125699
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125748
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.94	742	907	0.818	0.0000561	9937
Missense (PolyPhen)		259	372.31	0.69566		4109
Synonymous	-0.180	398	393	1.01	0.0000265	2945
Loss of Function	6.67	18	83.9	0.215	0.00000480	891

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00049	0.00049	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as molecular guidance cue in cellular migration, and function may be mediated by interaction with roundabout homolog receptors.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.150
RVIS EVS: -2.2
RVIS percentile EVS: 1.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.401

Gene Damage Prediction

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