FGFRL1

protein-coding

fibroblast growth factor receptor like 1, the group of I-set domain containing|Ig-like cell adhesion molecule family

Gene summary

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. A marked difference between this gene product and the other family members is its lack of a cytoplasmic tyrosine kinase domain. The result is a transmembrane receptor that could interact with other family members and potentially inhibit signaling. Multiple alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001004356.3

Inheritance

—

ClinVar variants

U:206B:124

Top phenotype

FGFRL1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr4:1,009,936-1,026,898

External References & Databases

Ensembl (ENSG00000127418)

Transcript & Mutation Effects

hg38 • Region Span ~17.0 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 FGFRL1 variants in ClinVar

7 Conditions Cataloged

not providedTotal: 289

not specifiedTotal: 122

FGFRL1-related disorderTotal: 20

4p partial monosomy syndromeTotal: 2

Congenital diaphragmatic herniaTotal: 2

MicrocephalyTotal: 1

Flexion contractureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001004356.3. 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				98 clinvar	10 clinvar	108
missense			197 clinvar	12 clinvar	2 clinvar	211
nonsense			1 clinvar			1
start loss						0
frameshift			6 clinvar	2 clinvar		8
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	206	112	12	330

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001004356.3	RefSeq	NP_001004356.1	6	MANE Select
ENST00000510644.6	Ensembl	ENSP00000425025.1	6	MANE Select
NM_001004358.1	RefSeq	NP_001004358.1	6	Standard
NM_001370296.1	RefSeq	NP_001357225.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fgfrl1b	Danio rerio	Structure: ceratobranchial cartilage Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

fgfrl1b

Danio rerio

Structure: ceratobranchial cartilage

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

VEGF Signaling Pathway
Signal Transduction
Signaling by FGFR
Signaling by Receptor Tyrosine Kinases
FGFRL1 modulation of FGFR1 signaling

Biological Process

skeletal system development
heart valve morphogenesis
negative regulation of cell population proliferation
fibroblast growth factor receptor signaling pathway
substrate adhesion-dependent cell spreading

Molecular Function

fibroblast growth factor-activated receptor activity
heparin binding
fibroblast growth factor binding

Cellular Component

Golgi apparatus
plasma membrane
integral component of membrane
transport vesicle
cell-cell contact zone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398484
Coding exons: 6
Length: 16962
Individuals with no LoFs: 125198
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125212
p: 0.0000559

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.248	341	354	0.963	0.0000260	3151
Missense (PolyPhen)		119	150.98	0.78816		1305
Synonymous	-2.30	210	172	1.22	0.0000140	1104
Loss of Function	2.35	6	16.2	0.370	8.48e-7	175

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00012	0.00010	rare
East Asian	0.00012	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has a negative effect on cell proliferation. {ECO:0000250}.;

Recessive Scores

pRec: 0.191

Intolerance Scores

LoFtool: 0.101
RVIS EVS: -0.77
RVIS percentile EVS: 13.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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