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FLASH GENE

Symbol

LRRC4

contributors: mct - updated : 31-10-2013

HGNC name	leucine rich repeat containing 4
HGNC id	15586

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	7q32.1      Physical location : 127.667.125 - 127.671.002
Synonym name	NAG14 protein
	brain tumor associated protein LRRC4
	brain tumor-associated protein BAG
	nasopharyngeal carcinoma-associated gene 14 protein
	netrin-G2 ligand
Synonym symbol(s)	NAG14, NGL-2

DNA

TYPE	functioning gene
STRUCTURE	3.88 kb     2 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_022143 2 - 3723 NP_071426 - 653 - 2004 15967442

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly   mouth       highly Nervous brain limbic system hippocampus dentate gyrus predominantly Homo sapiens   brain diencephalon thalamus nuclei highly Homo sapiens   brain hindbrain cerebellum   highly Homo sapiens Adult

cells

System Cell Pubmed Species Stage Rna symbol Nervous Purkinje cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text

brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

nine leucine rich repeats and an immunoglobulin domain

HOMOLOGY

Homologene

FAMILY

LRR superfamily

CATEGORY

regulatory , tumor suppressor

SUBCELLULAR LOCALIZATION	plasma membrane,junction
text	surface bound or soluble protein
	concentrated in distinct dendritic segments corresponding to the termination of netrin-G2-positive axons
	LRRC4, LRRC4B, LRRC4C are mainly localized to the postsynaptic side of excitatory synapses

basic FUNCTION	stimulates/disrupts the growth of embryonic thalamic axon, depending of its form, surface bound/soluble protein
	may play an important role in maintaining normal function and suppressing tumorigenesis in the central nervous system
	participates in the differentiation of neuron and glia cells
	regulate axonal outgrowth and lamina-specific dendritic segmentation, suggesting that the NGL-dependent adhesion system is important for the development of axons, dendrites, and synapses
	at least partially by down-regulating the STMN1expression, acts as a major glioma suppressor, induces cell cycle arrest and modulates the dynamic process of microtubulin, leading to the inhibition of glioma cell proliferation and growth
	key regulator of input-specific synapse development in the hippocampus
	is critical for pathway-specific synapse development and functional integration of distinct inputs
	is a central component of pathway-specific development in the outer retina

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interacts with NG1 via immunoglobulin domains
	interact with the presynaptic ligands netrin-G2
	interact with the abundant postsynaptic density (PSD) protein, DLG4, and other postsynaptic proteins, including NMDA receptors
	LRRC4 binds to the PDZ domain of PARD6A, and interacts with PARD3

cell & other

REGULATION

Other

down-regulated in primary brain tumors

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   LOI     epigenetically inactivated commonly in glioma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer brain glioma/neuroblstoma modulation of LRRC4 or STMN1 expression may be useful for design of new therapies for the intervention of glioma

ANIMAL & CELL MODELS

	in netrin-G1- and -G2-deficient mice, in which axonal path-finding is normal, the segmental distribution of NGL-1 and -2 is selectively disrupted, and the individual receptors are diffused along the dendrites
	in Ngl-2-/- mice, we find specific defects in the assembly of presynaptic ribbons in rods, indicating that reverse signaling of complexes involving NGL-2 regulates presynaptic maturation