LRFN5

protein-coding

leucine rich repeat and fibronectin type III domain containing 5, the group of Ig-like cell adhesion molecule family|Fibronectin type III domain containing|I-set domain containing

Gene summary

This gene encodes a protein that belongs to the leucine-rich repeat and fibronectin type III domain-containing family of proteins. A similar protein in mouse, a glycosylated transmembrane protein, is thought to function in presynaptic differentiation. [provided by RefSeq, Sep 2016]

Previous symbols:

C14orf146

MANE transcript

NM_152447.5

Inheritance

—

ClinVar variants

U:73B:12

Top phenotype

LRFN5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr14:41,606,876-41,904,549

External References & Databases

Ensembl (ENSG00000165379)

Transcript & Mutation Effects

hg38 • Region Span ~297.7 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 LRFN5 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 65

LRFN5-related disorderTotal: 12

not providedTotal: 2

Inborn genetic diseasesTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152447.5. 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	6 clinvar	4 clinvar	11
missense			71 clinvar	1 clinvar	1 clinvar	73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	73	7	5	85

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152447.5	RefSeq	NP_689660.2	4	MANE Select
ENST00000298119.9	Ensembl	ENSP00000298119.4	4	MANE Select
NM_001330106.2	RefSeq	NP_001317035.1	2	Standard
NM_001346173.2	RefSeq	NP_001333102.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

synaptic membrane adhesion
regulation of presynapse assembly

Cellular Component

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: ENST00000298119
Coding exons: 4
Length: 296980
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.78	288	386	0.746	0.0000200	4735
Missense (PolyPhen)		68	141.4	0.48091		1806
Synonymous	-0.439	151	144	1.05	0.00000748	1458
Loss of Function	3.29	4	19.8	0.202	0.00000102	267

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00013	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
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. {ECO:0000269|PubMed:18227064, ECO:0000269|PubMed:18585462}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.180
RVIS EVS: -0.87
RVIS percentile EVS: 10.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.134

Gene Damage Prediction

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