Human Gene FIG4 (ENST00000230124.8) from GENCODE V44
  Description: Homo sapiens FIG4 phosphoinositide 5-phosphatase (FIG4), mRNA. (from RefSeq NM_014845)
RefSeq Summary (NM_014845): 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].
Gencode Transcript: ENST00000230124.8
Gencode Gene: ENSG00000112367.12
Transcript (Including UTRs)
   Position: hg38 chr6:109,691,296-109,825,426 Size: 134,131 Total Exon Count: 23 Strand: +
Coding Region
   Position: hg38 chr6:109,691,436-109,825,265 Size: 133,830 Coding Exon Count: 23 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr6:109,691,296-109,825,426)mRNA (may differ from genome)Protein (907 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: FIG4_HUMAN
DESCRIPTION: RecName: Full=Polyphosphoinositide phosphatase; EC=3.1.3.-; AltName: Full=Phosphatidylinositol 3,5-bisphosphate 5-phosphatase; AltName: Full=SAC domain-containing protein 3;
FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). In vitro, hydrolyzes all three D5-phosphorylated polyphosphoinositide substrates in the order PtdIns(4,5)P2 > PtdIns(3,5)P2 > PtdIns(3,4,5)P3. Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.
SUBUNIT: Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold.
SUBCELLULAR LOCATION: Endosome membrane. Note=Localization requires VAC14 and PIKFYVE.
DISEASE: Defects in FIG4 are the cause of Charcot-Marie-Tooth disease type 4J (CMT4J) [MIM:611228]. CMT4J is a recessive demyelinating, severe form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy.
DISEASE: Defects in FIG4 are the cause of amyotrophic lateral sclerosis type 11 (ALS11) [MIM:612577]. ALS is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10%.
SIMILARITY: Contains 1 SAC domain.
SEQUENCE CAUTION: Sequence=BAA13403.2; Type=Erroneous initiation;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: FIG4
Diseases sorted by gene-association score: polymicrogyria, bilateral temporooccipital* (1629), yunis-varon syndrome* (1598), charcot-marie-tooth disease, type 4j* (1579), amyotrophic lateral sclerosis 11* (1235), charcot-marie-tooth neuropathy type 4j* (500), fig4-related amyotrophic lateral sclerosis* (500), amyotrophic lateral sclerosis 1* (100), neuropathy, congenital hypomyelinating* (34), tooth disease (13), polymicrogyria (12), charcot-marie-tooth disease (12), lateral sclerosis (10), cleidocranial dysplasia (9), amyotrophic lateral sclerosis 7 (6), amyotrophic lateral sclerosis type 10 (6), amyotrophic lateral sclerosis 9 (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 11.21 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 335.25 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -57.00140-0.407 Picture PostScript Text
3' UTR -25.80161-0.160 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002013 - Syja_N

Pfam Domains:
PF02383 - SacI homology domain

ModBase Predicted Comparative 3D Structure on Q92562
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologGenome BrowserNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD Ensembl  
Protein SequenceProtein Sequence Protein Sequence  
AlignmentAlignment Alignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004438 phosphatidylinositol-3-phosphatase activity
GO:0005515 protein binding
GO:0016787 hydrolase activity
GO:0034593 phosphatidylinositol bisphosphate phosphatase activity
GO:0042578 phosphoric ester hydrolase activity
GO:0043812 phosphatidylinositol-4-phosphate phosphatase activity
GO:0043813 phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity

Biological Process:
GO:0006661 phosphatidylinositol biosynthetic process
GO:0007033 vacuole organization
GO:0007626 locomotory behavior
GO:0010976 positive regulation of neuron projection development
GO:0016311 dephosphorylation
GO:0031642 negative regulation of myelination
GO:0032288 myelin assembly
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
GO:0043473 pigmentation
GO:0046488 phosphatidylinositol metabolic process
GO:0048666 neuron development

Cellular Component:
GO:0000139 Golgi membrane
GO:0005768 endosome
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005811 lipid particle
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0031901 early endosome membrane
GO:0031902 late endosome membrane
GO:0043231 intracellular membrane-bounded organelle
GO:0055037 recycling endosome


-  Descriptions from all associated GenBank mRNAs
  LF384629 - JP 2014500723-A/192132: Polycomb-Associated Non-Coding RNAs.
MA620206 - JP 2018138019-A/192132: Polycomb-Associated Non-Coding RNAs.
BC041338 - Homo sapiens FIG4 homolog (S. cerevisiae), mRNA (cDNA clone MGC:41828 IMAGE:5274004), complete cds.
AK291671 - Homo sapiens cDNA FLJ76880 complete cds.
AK293422 - Homo sapiens cDNA FLJ57101 complete cds, highly similar to SAC domain-containing protein 3.
D87464 - Homo sapiens mRNA for KIAA0274 gene.
AK222732 - Homo sapiens mRNA for Sac domain-containing inositol phosphatase 3 variant, clone: COL10284.
LF322305 - JP 2014500723-A/129808: Polycomb-Associated Non-Coding RNAs.
MA557882 - JP 2018138019-A/129808: Polycomb-Associated Non-Coding RNAs.
JD233734 - Sequence 214758 from Patent EP1572962.
JD550721 - Sequence 531745 from Patent EP1572962.
JD221252 - Sequence 202276 from Patent EP1572962.
LF322297 - JP 2014500723-A/129800: Polycomb-Associated Non-Coding RNAs.
MA557874 - JP 2018138019-A/129800: Polycomb-Associated Non-Coding RNAs.
LF322283 - JP 2014500723-A/129786: Polycomb-Associated Non-Coding RNAs.
MA557860 - JP 2018138019-A/129786: Polycomb-Associated Non-Coding RNAs.
LF322282 - JP 2014500723-A/129785: Polycomb-Associated Non-Coding RNAs.
MA557859 - JP 2018138019-A/129785: Polycomb-Associated Non-Coding RNAs.
LF322279 - JP 2014500723-A/129782: Polycomb-Associated Non-Coding RNAs.
MA557856 - JP 2018138019-A/129782: Polycomb-Associated Non-Coding RNAs.
LF322272 - JP 2014500723-A/129775: Polycomb-Associated Non-Coding RNAs.
MA557849 - JP 2018138019-A/129775: Polycomb-Associated Non-Coding RNAs.
JD345223 - Sequence 326247 from Patent EP1572962.
JD565175 - Sequence 546199 from Patent EP1572962.
JD154998 - Sequence 136022 from Patent EP1572962.
JD310471 - Sequence 291495 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
PWY-6352 - 3-phosphoinositide biosynthesis
PWY-6371 - superpathway of inositol phosphate compounds

Reactome (by CSHL, EBI, and GO)

Protein Q92562 (Reactome details) participates in the following event(s):

R-NUL-1675925 PI3P is phosphorylated to PI(3,5)P2 by Pikfyve at the late endosome membrane
R-NUL-1676051 PI is phosphorylated to PI5P by Pikfyve at the late endosome membrane
R-HSA-1675866 PI is phosphorylated to PI5P by PIKFYVE at the late endosome membrane
R-HSA-1676020 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the late endosome membrane
R-HSA-1675910 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the late endosome membrane
R-NUL-1675982 PI3P is phosphorylated to PI(3,5)P2 by Pikfyve at the Golgi membrane
R-HSA-1676005 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the Golgi membrane
R-HSA-1675921 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the Golgi membrane
R-HSA-1676174 PI(3,5)P2 is dephosphorylated to PI3P by FIG4 at the early endosome membrane
R-HSA-1676168 PI3P is phosphorylated to PI(3,5)P2 by PIKFYVE at the early endosome membrane
R-NUL-1675886 PI3P is phosphorylated to PI(3,5)P2 by Pikfyve at the early endosome membrane
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
R-HSA-1483255 PI Metabolism
R-HSA-1483257 Phospholipid metabolism
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000230124.1, ENST00000230124.2, ENST00000230124.3, ENST00000230124.4, ENST00000230124.5, ENST00000230124.6, ENST00000230124.7, FIG4_HUMAN, KIAA0274, NM_014845, Q53H49, Q5TCS6, Q92562, SAC3, uc003ptt.1, uc003ptt.2, uc003ptt.3, uc003ptt.4
UCSC ID: ENST00000230124.8
RefSeq Accession: NM_014845
Protein: Q92562 (aka FIG4_HUMAN)
CCDS: CCDS5078.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene FIG4:
als-overview (Amyotrophic Lateral Sclerosis Overview)
cmt (Charcot-Marie-Tooth Hereditary Neuropathy Overview)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.