FLRT1

protein-coding

fibronectin leucine rich transmembrane protein 1, the group of Fibronectin type III domain containing

Gene summary

This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]

MANE transcript

NM_013280.5

Inheritance

ClinVar variants

U:132B:64

Top phenotype

spastic paraplegia, optic atropy, and neuropathy

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr11:64,035,931-64,119,173

External References & Databases

Ensembl (ENSG00000126500)

Transcript & Mutation Effects

hg38 • Region Span ~83.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spastic paraplegia, optic atropy, and neuropathySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012297

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FLRT1 variants in ClinVar

5 Conditions Cataloged

Peripheral neuropathyTotal: 111

not specifiedTotal: 108

FLRT1-related disorderTotal: 16

not providedTotal: 12

Hereditary spastic paraplegiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013280.5. 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				43 clinvar	10 clinvar	53
missense			131 clinvar	10 clinvar	1 clinvar	142
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	132	53	11	196

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013280.5	RefSeq	NP_037412.2	1	MANE Select
ENST00000682287.1	Ensembl	ENSP00000507207.1	1	MANE Select
NM_001384466.1	RefSeq	NP_001371395.1	1	Standard
NM_001423967.1	RefSeq	NP_001410896.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
flrt1b	Danio rerio	Structure: whole organism Quality: viability abnormal

Gene / Model

Organism

Observed Phenotype

flrt1b

Danio rerio

Structure: whole organism

Quality: viability

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Signaling by FGFR
Signaling by Receptor Tyrosine Kinases
Downstream signaling of activated FGFR1
Signaling by FGFR1

Biological Process

cell adhesion
fibroblast growth factor receptor signaling pathway
dendrite development
positive regulation of synapse assembly
neuron projection extension

Molecular Function

fibroblast growth factor receptor binding
protein binding, bridging

Cellular Component

extracellular space
endoplasmic reticulum membrane
plasma membrane
integral component of plasma membrane
cell-cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246841
Coding exons: 1
Length: 15986
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125724
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.55	372	466	0.798	0.0000324	4352
Missense (PolyPhen)		91	151.31	0.60141		1472
Synonymous	0.532	213	223	0.955	0.0000168	1492
Loss of Function	2.60	3	13.2	0.227	5.66e-7	145

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0.000067	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in fibroblast growth factor-mediated signaling cascades that lead to the activation of MAP kinases. Promotes neurite outgrowth via FGFR1-mediated activation of downstream MAP kinases. Promotes an increase both in neurite number and in neurite length. May play a role in cell-cell adhesion and cell guidance via its interaction with ADGRL1/LPHN1 and ADGRL3. {ECO:0000250|UniProtKB:Q6RKD8}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.0504
RVIS EVS: -0.71
RVIS percentile EVS: 14.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.298

Gene Damage Prediction

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