LRFN3

protein-coding

leucine rich repeat and fibronectin type III domain containing 3, the group of Fibronectin type III domain containing|I-set domain containing|Ig-like cell adhesion molecule family

Gene summary

Predicted to be involved in regulation of presynapse assembly; regulation of synaptic membrane adhesion; and synaptic membrane adhesion. Predicted to be located in plasma membrane. Predicted to be active in cell surface and presynaptic active zone membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_024509.2

Inheritance

—

ClinVar variants

U:114B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:35,935,358-35,946,624

External References & Databases

Ensembl (ENSG00000126243)

Transcript & Mutation Effects

hg38 • Region Span ~11.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRFN3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024509.2. 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			3 clinvar			3
missense			111 clinvar	3 clinvar		114
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	114	3	0	117

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024509.2	RefSeq	NP_078785.1	2	MANE Select
ENST00000246529.4	Ensembl	ENSP00000246529.3	2	MANE Select
ENST00000588831.5	Ensembl	ENSP00000466989.1	2	Standard
ENST00000588831.6	Ensembl	ENSP00000466989.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Synaptic adhesion-like molecules
Protein-protein interactions at synapses

Biological Process

regulation of synaptic membrane adhesion
synaptic membrane adhesion
regulation of presynapse assembly

Cellular Component

plasma membrane
cell surface
cell junction
axon
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000588831
Coding exons: 2
Length: 10410
Individuals with no LoFs: 125608
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125634
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.24	307	439	0.699	0.0000331	3873
Missense (PolyPhen)		81	153.06	0.52919		1446
Synonymous	0.192	223	227	0.984	0.0000182	1533
Loss of Function	3.10	0	11.2	0.00	4.79e-7	121

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00066	0.00062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000095	0.000088	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell adhesion molecule that mediates homophilic cell- cell adhesion in a Ca(2+)-independent manner. Promotes neurite outgrowth in hippocampal neurons (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.186
RVIS EVS: -0.42
RVIS percentile EVS: 25.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.390

Gene Damage Prediction

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