FIG4 FIG4 phosphoinositide 5-phosphatase [Homo sapiens (human)] - Gene

Summary

Official Symbol: FIG4provided by HGNC
Official Full Name: FIG4 phosphoinositide 5-phosphataseprovided by HGNC
Primary source: HGNC:HGNC:16873
See related: Ensembl:ENSG00000112367 MIM:609390; AllianceGenome:HGNC:16873
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: BOP; YVS; BTOP; SAC3; ALS11; CMT4J; KIAA0274; dJ249I4.1
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]
Expression: Ubiquitous expression in brain (RPKM 6.2), lung (RPKM 4.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q21

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (109691296..109825426)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (110869350..111003788)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (110012499..110146629)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Clinical and genetic features of patients suffering from CMT4J.
Title: Clinical and genetic features of patients suffering from CMT4J.
PROK2, HRNR, and FIG4 as potential genetic biomarkers of high bleeding propensity in East Asian patients with acute coronary syndrome using ticagrelor.
Title: PROK2, HRNR, and FIG4 as potential genetic biomarkers of high bleeding propensity in East Asian patients with acute coronary syndrome using ticagrelor.
Proximity Interactome Map of the Vac14-Fig4 Complex Using BioID.
Title: Proximity Interactome Map of the Vac14-Fig4 Complex Using BioID.
Clinical features of homozygous FIG4-p.Ile41Thr Charcot-Marie-Tooth 4J patients.
Title: Clinical features of homozygous FIG4-p.Ile41Thr Charcot-Marie-Tooth 4J patients.
Clinical and radiological characterization of novel FIG4-related combined system disease with neuropathy.
Title: Clinical and radiological characterization of novel FIG4-related combined system disease with neuropathy.
Severe Consequences SAC3/FIG4 Phosphatase Deficiency to Phosphoinositides in Patients with Charcot-Marie-Tooth Disease Type-4J.
Title: Severe Consequences of SAC3/FIG4 Phosphatase Deficiency to Phosphoinositides in Patients with Charcot-Marie-Tooth Disease Type-4J.
we identified four families with novel FIG4 genotypes and CNS white matter disease varying from severe hypomyelination to mild undermyelination, in addition to peripheral neuropathy. Impaired FIG4 function was revealed by the presence of large vacuoles in cultured patient fibroblasts
Title: Cerebral hypomyelination associated with biallelic variants of FIG4.
These findings strongly indicate a critical dependence of FIG4 for the normal functions of peripheral nerve myelin.
Title: Myelin abnormality in Charcot-Marie-Tooth type 4J recapitulates features of acquired demyelination.
in the adult PNS Fig4 is required to protect myelinated axons from Wallerian degeneration. In the adult CNS, Fig4 is dispensable for fiber stability and nerve conduction, but is required for the timely repair of damaged white matter. The greater vulnerability of the PNS to Fig4 deficiency in the mouse is consistent with clinical observations in patients with Charcot-Marie-Tooth disease.
Title: Protective role of the lipid phosphatase Fig4 in the adult nervous system.
A rare heterozygous FIG4 frameshift variant was identified in a German family. Sequence analysis of FIG4 in 200 ALS cases revealed five rare heterozygous FIG4 missense variants predicted to be deleterious. FIG4 is an ALS risk gene in a central European cohort.
Title: FIG4 variants in central European patients with amyotrophic lateral sclerosis: a whole-exome and targeted sequencing study.

Submit: New GeneRIF Correction See all GeneRIFs (26)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Amyotrophic lateral sclerosis type 11 MedGen: C2675491 OMIM: 612577 GeneReviews: Amyotrophic Lateral Sclerosis Overview	not available
Bilateral parasagittal parieto-occipital polymicrogyria MedGen: C4013648 OMIM: 612691 GeneReviews: Not available	not available
Charcot-Marie-Tooth disease type 4J MedGen: C1970011 OMIM: 611228 GeneReviews: Charcot-Marie-Tooth Hereditary Neuropathy Overview	not available
Yunis-Varon syndrome MedGen: C1857663 OMIM: 216340 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See Variation Viewer (GRCh37.p13)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G59323 (e-PCR)
- UniSTS:136489

SHGC-145585 (e-PCR)
- UniSTS:174662

RH119720 (e-PCR)
- UniSTS:133089

D6S2073 (e-PCR)
- UniSTS:1516

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity	TAS Traceable Author Statement more info
enables phosphatidylinositol-3-phosphate phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-4-phosphate phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine phosphatase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in locomotory behavior	IEA Inferred from Electronic Annotation more info
involved_in myelin assembly	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of myelination	IEA Inferred from Electronic Annotation more info
involved_in neuron development	IEA Inferred from Electronic Annotation more info
involved_in phosphatidylinositol biosynthetic process	TAS Traceable Author Statement more info
involved_in phosphatidylinositol dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol-3-phosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in pigmentation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron projection development	IEA Inferred from Electronic Annotation more info
involved_in vacuole organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in early endosome membrane	TAS Traceable Author Statement more info
located_in endosome membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in intracellular membrane-bounded organelle	IBA Inferred from Biological aspect of Ancestor more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in late endosome membrane	TAS Traceable Author Statement more info
located_in lipid droplet	IDA Inferred from Direct Assay more info
located_in recycling endosome	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: polyphosphoinositide phosphatase

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

NP_055660.1

EC 3.1.3.16

EC 3.1.3.36

EC 3.1.3.86

XP_011534583.1

EC 3.1.3.16

EC 3.1.3.36

EC 3.1.3.86

XP_054212880.1

EC 3.1.3.16

EC 3.1.3.36

EC 3.1.3.86

NCBI Reference Sequences (RefSeq)

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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), LRG_241

mRNA and Protein(s)

NM_014845.6 → NP_055660.1 polyphosphoinositide phosphatase

See identical proteins and their annotated locations for NP_055660.1

Status: REVIEWED

Source sequence(s)

AK222732, BC041338, BU683891, DA811740

Consensus CDS

CCDS5078.1

UniProtKB/Swiss-Prot

Q53H49, Q5TCS6, Q92562

UniProtKB/TrEMBL

A0A6Q8PF62

Related

ENSP00000230124.4, ENST00000230124.8

Conserved Domains (2) summary

COG5329
Location:14 → 636

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

pfam02383
Location:93 → 423

Syja_N; SacI homology domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

109691296..109825426

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011536281.4 → XP_011534583.1 polyphosphoinositide phosphatase isoform X1

UniProtKB/TrEMBL

A0A6Q8PF62

Conserved Domains (1) summary

pfam02383
Location:72 → 402

Syja_N; SacI homology domain