Human Gene GPHN (ENST00000315266.9)
  Description: Homo sapiens gephyrin (GPHN), transcript variant 8, mRNA. (from RefSeq NM_001377519)
RefSeq Summary (NM_001024218): This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000315266.9
Gencode Gene: ENSG00000171723.16
Transcript (Including UTRs)
   Position: hg38 chr14:66,507,407-67,181,798 Size: 674,392 Total Exon Count: 22 Strand: +
Coding Region
   Position: hg38 chr14:66,508,528-67,180,937 Size: 672,410 Coding Exon Count: 22 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr14:66,507,407-67,181,798)mRNA (may differ from genome)Protein (736 aa)
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ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: GEPH_HUMAN
DESCRIPTION: RecName: Full=Gephyrin; Includes: RecName: Full=Molybdopterin adenylyltransferase; Short=MPT adenylyltransferase; EC=2.7.7.75; AltName: Full=Domain G; Includes: RecName: Full=Molybdopterin molybdenumtransferase; Short=MPT Mo-transferase; EC=2.10.1.1; AltName: Full=Domain E;
FUNCTION: Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.
CATALYTIC ACTIVITY: ATP + molybdopterin = diphosphate + adenylyl- molybdopterin.
CATALYTIC ACTIVITY: Adenylyl-molybdopterin + molybdate = molybdenum cofactor + AMP.
COFACTOR: Magnesium (By similarity).
ENZYME REGULATION: Inhibited by copper and tungsten (By similarity).
PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis.
SUBUNIT: Homotrimer. Interacts with GABARAP (By similarity). Interacts with SRGAP2 (via SH3 domain) (By similarity).
SUBCELLULAR LOCATION: Cell junction, synapse (By similarity). Cell junction, synapse, postsynaptic cell membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Cytoplasm, cytoskeleton (By similarity). Note=Cytoplasmic face of glycinergic postsynaptic membranes (By similarity).
DISEASE: Defects in GPHN are the cause of molybdenum cofactor deficiency type C (MOCOD type C) [MIM:252150]. MOCOD type C is an autosomal recessive disease which leads to the pleiotropic loss of all molybdoenzyme activities and is characterized by severe neurological damage, neonatal seizures and early childhood death.
SIMILARITY: In the N-terminal section; belongs to the MoaB/Mog family.
SIMILARITY: In the C-terminal section; belongs to the MoeA family.
SEQUENCE CAUTION: Sequence=BAA92623.1; Type=Erroneous initiation;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GPHNID317.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GPHN";

-  MalaCards Disease Associations
  MalaCards Gene Search: GPHN
Diseases sorted by gene-association score: molybdenum cofactor deficiency c* (1650), hyperekplexia* (193), gphn-related hyperekplexia* (100), molybdenum cofactor deficiency (36), stiff-person syndrome (16), geniculate herpes zoster (11), charcot-marie-tooth disease, type 2d (9), spastic paraplegia 24, autosomal recessive (7), mediastinal cancer (7), acute monoblastic leukemia (6), autism spectrum disorder (2)
* = 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: 18.55 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 250.24 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 -471.201121-0.420 Picture PostScript Text
3' UTR -192.30861-0.223 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
IPR020817 - Mo_cofactor_synthesis
IPR008284 - MoCF_biosynth_CS
IPR005111 - MoeA_C_domain_IV
IPR005110 - MoeA_linker/N
IPR001453 - Mopterin-bd

Pfam Domains:
PF00994 - Probable molybdopterin binding domain
PF03454 - MoeA C-terminal region (domain IV)
PF03453 - MoeA N-terminal region (domain I and II)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1JLJ
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9NQX3
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 orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008940 nitrate reductase activity
GO:0016740 transferase activity
GO:0043546 molybdopterin cofactor binding
GO:0046872 metal ion binding
GO:0061598 molybdopterin adenylyltransferase activity
GO:0061599 molybdopterin molybdotransferase activity

Biological Process:
GO:0006777 Mo-molybdopterin cofactor biosynthetic process
GO:0008152 metabolic process
GO:0010038 response to metal ion
GO:0018315 molybdenum incorporation into molybdenum-molybdopterin complex
GO:0032324 molybdopterin cofactor biosynthetic process
GO:0055114 oxidation-reduction process
GO:0072579 glycine receptor clustering
GO:0097112 gamma-aminobutyric acid receptor clustering

Cellular Component:
GO:0005737 cytoplasm
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0030054 cell junction
GO:0030425 dendrite
GO:0042995 cell projection
GO:0045202 synapse
GO:0045211 postsynaptic membrane


-  Descriptions from all associated GenBank mRNAs
  AB037806 - Homo sapiens KIAA1385 mRNA for KIAA1385 protein.
AF272663 - Homo sapiens gephyrin mRNA, complete cds.
AK315569 - Homo sapiens cDNA, FLJ96642, highly similar to Homo sapiens gephyrin (GPHN), mRNA.
AJ272343 - Homo sapiens mRNA for gephyrin (GPHN gene).
AK294532 - Homo sapiens cDNA FLJ54713 complete cds, highly similar to Gephyrin.
AK297447 - Homo sapiens cDNA FLJ54094 complete cds, highly similar to Gephyrin.
BC030016 - Homo sapiens gephyrin, mRNA (cDNA clone MGC:32983 IMAGE:4826821), complete cds.
DQ892463 - Synthetic construct clone IMAGE:100005093; FLH186553.01X; RZPDo839F0971D gephyrin (GPHN) gene, encodes complete protein.
DQ895675 - Synthetic construct Homo sapiens clone IMAGE:100010135; FLH186549.01L; RZPDo839F0961D gephyrin (GPHN) gene, encodes complete protein.
AB385462 - Synthetic construct DNA, clone: pF1KA1385, Homo sapiens GPHN gene for gephyrin, complete cds, without stop codon, in Flexi system.
AJ272033 - Homo sapiens mRNA for gephyrin (GPHRYN gene).
AK295577 - Homo sapiens cDNA FLJ54093 complete cds, highly similar to Gephyrin.
AK025169 - Homo sapiens cDNA: FLJ21516 fis, clone COL05824.
JD197517 - Sequence 178541 from Patent EP1572962.
JD147139 - Sequence 128163 from Patent EP1572962.
JD244207 - Sequence 225231 from Patent EP1572962.
JD302542 - Sequence 283566 from Patent EP1572962.
JD349457 - Sequence 330481 from Patent EP1572962.
JD328194 - Sequence 309218 from Patent EP1572962.
JD556163 - Sequence 537187 from Patent EP1572962.
JD508499 - Sequence 489523 from Patent EP1572962.
JD102552 - Sequence 83576 from Patent EP1572962.
JD424398 - Sequence 405422 from Patent EP1572962.
JD042617 - Sequence 23641 from Patent EP1572962.
JD261100 - Sequence 242124 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_gabaPathway - Gamma-aminobutyric Acid Receptor Life Cycle

Reactome (by CSHL, EBI, and GO)

Protein Q9NQX3 (Reactome details) participates in the following event(s):

R-HSA-947531 Molybdenum ion transfer onto molybdopterin
R-HSA-947581 Molybdenum cofactor biosynthesis
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000315266.1, ENST00000315266.2, ENST00000315266.3, ENST00000315266.4, ENST00000315266.5, ENST00000315266.6, ENST00000315266.7, ENST00000315266.8, GEPH_HUMAN, GPH, KIAA1385, NM_001377519, Q9H4E9, Q9NQX3, Q9P2G2, uc001xiy.1, uc001xiy.2, uc001xiy.3, uc001xiy.4
UCSC ID: ENST00000315266.9
RefSeq Accession: NM_001024218
Protein: Q9NQX3 (aka GEPH_HUMAN)
CCDS: CCDS9777.1, CCDS32103.1

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