FIG4 FIG4 homolog, SAC1 lipid phosphatase domain containing (S. cerevisiae) [Homo sapiens] - Gene

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Summary

Official Symbol: FIG4provided by HGNC
Official Full Name: FIG4 homolog, SAC1 lipid phosphatase domain containing (S. cerevisiae)provided by HGNC
Primary source: HGNC:16873
Locus tag: RP1-249I4.1
See related: Ensembl:ENSG00000112367; HPRD:11073; MIM:609390; Vega:OTTHUMG00000015352
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SAC3; ALS11; CMT4J; KIAA0274; dJ249I4.1; RP1-249I4.1; KIAA0274
Summary: The protein encoded by this gene belongs to the SAC domain-containing protein gene family. The SAC domain, approximately 400 amino acids in length and consisting of seven conserved motifs, has been shown to possess phosphoinositide phosphatase activity. The yeast homolog, Sac1p, is involved in the regulation of various phosphoinositides, and affects diverse cellular functions such as actin cytoskeleton organization, Golgi function, and maintenance of vacuole morphology. Membrane-bound phosphoinositides function as signaling molecules and play a key role in vesicle trafficking in eukaryotic cells. Mutations in this gene have been associated with Charcot-Marie-Tooth disease, type 4J. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 6q21

Sequence :: Chromosome: 6; NC_000006.11 (110012424..110146634)

See FIG4 in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

This study demonistrated that CMT4J is a clinically distinct form of Charcot-Marie-Tooth disease with mutations in the PI(3,5)P phosphatase FIG4.
Title: Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P₂ phosphatase FIG4.
a novel regulatory mechanism whereby ArPIKfyve enhances Sac3 abundance by attenuating Sac3 proteasome-dependent degradation and suggest that a failure of this mechanism could be the primary molecular defect in the pathogenesis of CMT4J.
Title: ArPIKfyve regulates Sac3 protein abundance and turnover: disruption of the mechanism by Sac3I41T mutation causing Charcot-Marie-Tooth 4J disorder.
PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis
Title: PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis.
Observational study of gene-disease association. (HuGE Navigator)
Title: FUS, TARDBP, and SOD1 mutations in a Taiwanese cohort with familial ALS.
Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases
Title: Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS.
The authors data indicate that the PAS complex is organized to provide optimal PIKfyve functionality and is maintained via ArPIKfyve homomeric and heteromeric interactions.
Title: ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality.
We identified pathogenic mutations of human FIG4 (KIAA0274) on chromosome 6q21 in four unrelated patients with hereditary motor and sensory neuropathy.
Title: Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J.

Submit: New GeneRIF Correction

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.

Amyotrophic lateral sclerosis 11

MIM: 612577

Charcot-Marie-Tooth disease, type 4J

MIM: 611228

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
BioGRID:115225	BioGRID:113164	UBC		BioGRID	PubMed	Affinity Capture-MS
BioGRID:115225	BioGRID:120822	VAC14		BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
hydrolase activity	IEA Inferred from Electronic Annotation more info
phosphoric ester hydrolase activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
cell death	IEA Inferred from Electronic Annotation more info
locomotory behavior	IEA Inferred from Electronic Annotation more info
neuron development	IEA Inferred from Electronic Annotation more info
phosphatidylinositol metabolic process	IEA Inferred from Electronic Annotation more info
pigmentation	IEA Inferred from Electronic Annotation more info
positive regulation of neuron projection development	IEA Inferred from Electronic Annotation more info
vacuole organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi apparatus	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
endosome membrane	IDA Inferred from Direct Assay more info	PubMed
membrane	IEA Inferred from Electronic Annotation more info
recycling endosome	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: polyphosphoinositide phosphatase

Names: polyphosphoinositide phosphatase; SAC domain-containing protein 3; Sac domain-containing inositol phosphatase 3; phosphatidylinositol 3,5-bisphosphate 5-phosphatase; FIG4 homolog, SAC domain containing lipid phosphatase; FIG4 homolog, SAC1 domain containing lipid phosphatase

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007977.1 RefSeqGene

Range

5001..139211

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_014845.5 → NP_055660.1 polyphosphoinositide phosphatase

Status: REVIEWED

Source sequence(s)

AK222732, BC041338, BU683891, DA811740

Consensus CDS

CCDS5078.1

UniProtKB/Swiss-Prot

Q92562

Related

ENSP00000230124, OTTHUMP00000016976, ENST00000230124, OTTHUMT00000041768

Conserved Domains (2) summary

COG5329
Location:14 – 641
Blast Score: 718

COG5329; Phosphoinositide polyphosphatase (Sac family) [Signal transduction mechanisms]

pfam02383
Location:92 – 423
Blast Score: 813

Syja_N; SacI homology domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p5 Primary Assembly

Range

110012424..110146634

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

107578606..107713071

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL133472.12	CAI19669.1
		CAI19670.1
		CAI19671.1
genomic	AL512303.10	CAI42493.1
		CAI42494.1
		CAI42495.1
genomic	CH471051.2	EAW48332.1
mRNA	AA815086.1	None
mRNA	AA946705.1	None
mRNA	AI476769.1	None
mRNA	AK222732.1	BAD96452.1
mRNA	AK291671.1	BAF84360.1
mRNA	AK293422.1	BAG56929.1
mRNA	BC041338.2	AAH41338.1
mRNA	BM016965.1	None
mRNA	BU683891.1	None
mRNA	D87464.1	BAA13403.2
mRNA	DA811740.1	None

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q5JRV4	GenPept	UniProtKB/TrEMBL:Q5JRV4
Q5TCS4	GenPept	UniProtKB/TrEMBL:Q5TCS4
Q5TCS5	GenPept	UniProtKB/TrEMBL:Q5TCS5
Q92562.1	GenPept	UniProtKB/Swiss-Prot:Q92562