LRFN4

protein-coding

leucine rich repeat and fibronectin type III domain containing 4, 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 postsynaptic density assembly; regulation of presynapse assembly; and synaptic membrane adhesion. Predicted to be located in plasma membrane. Predicted to be active in cell surface; glutamatergic synapse; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_024036.5

Inheritance

—

ClinVar variants

P:1U:105B:4

Top phenotype

Pyruvate carboxylase deficiency

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr11:66,856,647-66,860,475

External References & Databases

Ensembl (ENSG00000173621)

Transcript & Mutation Effects

hg38 • Region Span ~3.8 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 LRFN4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 4

Pyruvate carboxylase deficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024036.5. 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			1 clinvar	4 clinvar		5
missense			104 clinvar			104
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	105	4	0	110

Highest pathogenic variant AF is 0.000002585887

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024036.5	RefSeq	NP_076941.2	2	MANE Select
ENST00000309602.5	Ensembl	ENSP00000312535.4	2	MANE Select
NM_001363524.2	RefSeq	NP_001350453.1	2	Standard
ENST00000393952.3	Ensembl	ENSP00000377524.3	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 postsynaptic density assembly
synaptic membrane adhesion
regulation of presynapse assembly

Molecular Function

protein binding

Cellular Component

plasma membrane
cell surface
glutamatergic synapse
GABA-ergic synapse
integral component of postsynaptic density membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309602
Coding exons: 2
Length: 3829
Individuals with no LoFs: 125348
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125357
p: 0.0000359

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.25	347	419	0.828	0.0000305	3893
Missense (PolyPhen)		102	158.2	0.64477		1669
Synonymous	-0.928	220	203	1.08	0.0000155	1500
Loss of Function	2.98	1	12.2	0.0816	6.81e-7	123

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000032	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000056	0.000053	rare
South Asian	0.000041	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes neurite outgrowth in hippocampal neurons. May play a role in redistributing DLG4 to the cell periphery (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.112

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.354

Gene Damage Prediction

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