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FLASH GENE

Symbol

FIG4

contributors: mct - updated : 25-01-2014

HGNC name	FIG4 homolog (S. cerevisiae)
HGNC id	16873

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CMT4J Charcot-Marie-Tooth disease, type J YVS Yunis-Varon syndrome
Location	6q21      Physical location : 110.012.423 - 110.146.634
Synonym name	sac domain-containing inositol phosphatase 3
	FIG4 homolog
	KIAA0274 protein
Synonym symbol(s)	SAC3, hSac3, dJ249I4.1, KIAA0274, RP1-249I4.1

DNA

TYPE	functioning gene
STRUCTURE	134.00 kb     23 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_014845 23 - 3089 NP_055660 103 907 - 2007 17909536

EXPRESSION

Type	ubiquitous

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 mouth tongue     moderately Lymphoid/Immune spleen       highly Respiratory respiratory tract larynx     moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Nervous astrocyte Homo sapiens Nervous neuron Homo sapiens

cell lineage
cell lines
fluid/secretion	blood

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a SAC domain

HOMOLOGY

interspecies

homolog to S. cerevisiae FIG4

Homologene

FAMILY

PIPPase family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi

basic FUNCTION	promotes neurite outgrowth in differentiating neurons through its PIPPase activity, suggesting that Sac domain PIPPase proteins may participate in forward membrane trafficking from the endoplasmic reticulum and Golgi complex to the plasma membrane, and may function as regulators of this crucial process of neuronal cell growth and differentiation
	assembled in the PAS regulatory core complex is an active PtdIns(3,5)P(2) phosphatase
	with PIKFYVE, constitute a single multiprotein complex organized by the PIKFYVE regulator VAC14 and its ability to homodimerize
	expression of FIG4 in neurons is necessary and sufficient to prevent spongiform degeneration
	lipid phosphatase that regulates intracellular abundance of the signaling phospholipid PI(3,5)P2
	phosphoinositide phosphatase required for regulation of PI(3,5)P2 levels, and thus endosomal trafficking and autophagy
	VAC14 acts in a complex with the lipid kinase PIKFYVE and its counteracting phosphatase FIG4, regulating the interconversion of phosphatidylinositol-3-phosphate to phosphatidylinositol-3,5-bisphosphate

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein

interacting with VAC14 (enhances FIG4 abundance by attenuating FIG4 proteasome-dependent degradation)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CMT4J , YVS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function results in spongiform degeneration

Susceptibility

to amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS)

Variant & Polymorphism other	allele of FIG4 appears to be a risk factor for ALS and PLS

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	homozygous Fig4-null mice exhibit features of YVS, including neurodegeneration and enlarged vacuoles in neurons
	null mutation of Fig4 in the mouse results in spongiform degeneration of brain and peripheral ganglia, defective myelination and juvenile lethality