FLRT3 (fibronectin leucine rich transmembrane protein 3)

Gene

• Entrez ID: 23767
• Gene name: Fibronectin leucine rich transmembrane protein 3
• Gene symbol: FLRT3
• Synonyms (NCBI Gene): HH21
• Chromosome: 20
• Chromosome location: 20p12.1
• Summary: This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. FLRTs may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular m

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1996037	hsa-miR-323b-3p	CLIP-seq
MIRT1996038	hsa-miR-450b-5p	CLIP-seq
MIRT1996039	hsa-miR-4708-3p	CLIP-seq
MIRT1996040	hsa-miR-3065-5p	CLIP-seq
MIRT1996041	hsa-miR-3647-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003345	Process	Proepicardium cell migration involved in pericardium morphogenesis	IEA
GO:0003345	Process	Proepicardium cell migration involved in pericardium morphogenesis	ISS
GO:0005104	Function	Fibroblast growth factor receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	26235030, 26960425
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IDA	14706654, 26235030
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	NAS	10644439
GO:0005886	Component	Plasma membrane	TAS
GO:0005911	Component	Cell-cell junction	IEA
GO:0005925	Component	Focal adhesion	IEA
GO:0005925	Component	Focal adhesion	IEA
GO:0007155	Process	Cell adhesion	IEA
GO:0007411	Process	Axon guidance	IEA
GO:0007411	Process	Axon guidance	IEA
GO:0007416	Process	Synapse assembly	IEA
GO:0007416	Process	Synapse assembly	ISS
GO:0007507	Process	Heart development	IEA
GO:0007507	Process	Heart development	ISS
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IEA
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	ISS
GO:0016020	Component	Membrane	IEA
GO:0030054	Component	Cell junction	IDA
GO:0030054	Component	Cell junction	IEA
GO:0030424	Component	Axon	IEA
GO:0030674	Function	Protein-macromolecule adaptor activity	NAS	10644439
GO:0031012	Component	Extracellular matrix	NAS	10644439
GO:0031175	Process	Neuron projection development	IEA
GO:0031175	Process	Neuron projection development	ISS
GO:0032584	Component	Growth cone membrane	IEA
GO:0042734	Component	Presynaptic membrane	IEA
GO:0042803	Function	Protein homodimerization activity	IDA	26235030
GO:0042995	Component	Cell projection	IEA
GO:0043679	Component	Axon terminus	IEA
GO:0043679	Component	Axon terminus	ISS
GO:0044295	Component	Axonal growth cone	IEA
GO:0044295	Component	Axonal growth cone	ISS
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0045499	Function	Chemorepellent activity	IEA
GO:0048598	Process	Embryonic morphogenesis	IEA
GO:0048598	Process	Embryonic morphogenesis	ISS
GO:0048678	Process	Response to axon injury	IEA
GO:0048678	Process	Response to axon injury	ISS
GO:0050919	Process	Negative chemotaxis	IEA
GO:0051965	Process	Positive regulation of synapse assembly	IEA
GO:0060322	Process	Head development	IEA
GO:0060322	Process	Head development	ISS
GO:0070161	Component	Anchoring junction	IEA
GO:0097060	Component	Synaptic membrane	IEA
GO:0097060	Component	Synaptic membrane	ISS
GO:0098742	Process	Cell-cell adhesion via plasma-membrane adhesion molecules	IDA	26235030
GO:0098742	Process	Cell-cell adhesion via plasma-membrane adhesion molecules	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099560	Process	Synaptic membrane adhesion	IEA
GO:1990138	Process	Neuron projection extension	IEA
GO:1990138	Process	Neuron projection extension	IMP	14706654
GO:1990138	Process	Neuron projection extension	ISS

Other IDs

• MIM: 604808
• HGNC: 3762
• e!Ensembl: ENSG00000125848

Protein

• UniProt ID: Q9NZU0
• Protein name: Leucine-rich repeat transmembrane protein FLRT3 (Fibronectin-like domain-containing leucine-rich transmembrane protein 3)
• Protein function: Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners. Plays a role in the spatial organization of brain neurons. Plays a role in vascular development in
• PDB: 5CMN, 5CMP, 6JBU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13855	LRR_8	175 → 237	Leucine rich repeat	Repeat
  PF13855	LRR_8	247 → 306	Leucine rich repeat	Repeat

• Tissue specificity: TISSUE SPECIFICITY: Expressed in kidney, brain, pancreas, skeletal muscle, lung, liver, placenta, and heart. {ECO:0000269|PubMed:10644439}.
• Sequence:

  MISAAWSIFLIGTKIGLFLQVAPLSVMAKSCPSVCRCDAGFIYCNDRFLTSIPTGIPEDA
  TTLYLQNNQINNAGIPSDLKNLLKVERIYLYHNSLDEFPTNLPKYVKELHLQENNIRTIT
  YDSLSKIPYLEELHLDDNSVSAVSIEEGAFRDSNYLRLLFLSRNHLSTIPWGLPRTIEEL
  RLDDNRISTISSPSLQGLTSLKRLVLDGNLLNNHGLGDKVFFNLVNLTELSLVRNSLTAA
  PVNLPGTNLRKLYLQDNHINRVPPNAFSYLRQLYRLDMSNNNLSNLPQGIFDDLDNITQL
  ILRNNPWYCGCKMKWVRDWLQSLPVKVNVRGLMCQAPEKVRGMAIKDLNAELFDCKDSGI
  VSTIQITTAIPNTVYPAQGQWPAPVTKQPDIKNPKLTKDHQTTGSPSRKTITITVKSVTS
  DTIHISWKLALPMTALRLSWLKLGHSPAFGSITETIVTGERSEYLVTALEPDSPYKVCMV
  PMETSNLYLFDETPVCIETETAPLRMYNPTTTLNREQEKEPYKNPNLPLAAIIGGAVALV
  TIALLALVCWYVHRNGSLFSRNCAYSKGRRRKDDYAEAGTKKDNSILEIRETSFQMLPIS
  NEPISKEEFVIHTIFPPNGMNLYKNNHSESSSNRSYRDSGIPDSDHSHS

• Sequence length: 649

Pathways

Reactome:

Downstream signaling of activated FGFR1

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hypogonadotropic hypogonadism 21 with or without anosmia	Pathogenic	rs398124654	RCV000043605	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Disorder of sexual differentiation	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FLRT3-related disorder	Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
High myopia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOGONADOTROPIC HYPOGONADISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOGONADOTROPIC HYPOGONADISM 21 WITH ANOSMIA, SUSCEPTIBILITY TO	risk factor	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOPITUITARISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IDIOPATHIC GROWTH HORMONE DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KALLMANN SYNDROME	—	Disgenet, GenCC, Orphanet Disgenet, GenCC, Orphanet Disgenet, GenCC, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOOD DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANHYPOPITUITARISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY DWARFISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY SHORT STATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE MYOPIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SHEEHAN SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anterior hypopituitarism	Hypopituitarism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	22939004, 30110355		★☆☆☆☆ Found in Text Mining only
Behcet Syndrome	Behcet disease	Pubtator	39191728	Inhibit	★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar disorder	Pubtator	39191728	Associate	★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	35560224	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	37689589	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	35676660	Associate	★☆☆☆☆ Found in Text Mining only
Cartilage-hair hypoplasia	Cartilage-Hair Hypoplasia	BEFREE	23643382		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	35560224	Associate	★☆☆☆☆ Found in Text Mining only
Congenital absence of kidneys syndrome	Renal agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypogonadotropic hypogonadism	Congenital Hypogonadotropic Hypogonadism	BEFREE	23643382		★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of breast	Breast hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gynecomastia	Gynecomastia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	Pubtator	37108593	Associate	★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOGONADOTROPIC HYPOGONADISM 21 WITH OR WITHOUT ANOSMIA	Hypogonadotropic Hypogonadism With Or Without Anosmia	GENOMICS_ENGLAND_DG	21700882		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPOGONADOTROPIC HYPOGONADISM 21 WITH OR WITHOUT ANOSMIA	Hypogonadotropic Hypogonadism With Or Without Anosmia	UNIPROT_DG	23643382		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPOGONADOTROPIC HYPOGONADISM 21 WITH OR WITHOUT ANOSMIA	Hypogonadotropic Hypogonadism With Or Without Anosmia	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPOGONADOTROPIC HYPOGONADISM 21 WITH OR WITHOUT ANOSMIA	Hypogonadotropic Hypogonadism With Or Without Anosmia	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ichthyoses	Ichthyosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Idiopathic Hypogonadotropic Hypogonadism	Hypogonadotropic hypogonadism	Pubtator	36700485	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Kallmann Syndrome	Kallmann Syndrome	ORPHANET_DG	23643382		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kallmann syndrome	Kallmann Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kallmann Syndrome	Kallmann syndrome	Pubtator	37108593	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mirror movements disorder	Mirror Movements	HPO_DG			★☆☆☆☆ Found in Text Mining only
Miscarriage	Miscarriage	CTD_human_DG	18539642		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	40037332	Associate	★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteochondrodysplasias	Osteochondrodysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paraplegia	Paraplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skeletal dysplasia	Skeletal Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only