RALGAPA1 Gene (Protein Coding)

Ral GTPase Activating Protein Catalytic Subunit Alpha 1

GC14M035538
GIFtS:
40
This gene encodes a major subunit of the RAL-GTPase activating protein. A similar protein in mouse binds E12, a transcriptional regulator of immunoglobulin genes. The mouse protein also functions in skeletal muscle by binding to the regulatory 14-3-3 proteins upon stimulation with insulin or muscle contraction. A pseudogene of this gene has been identified on chromosome 9. [pro... See more...

Aliases for RALGAPA1 Gene

Aliases for RALGAPA1 Gene

  • Ral GTPase Activating Protein Catalytic Subunit Alpha 1 2 3 5
  • Tuberin-Like Protein 1 2 3 4
  • GRIPE 2 3 4
  • Ral GTPase-Activating Protein Subunit Alpha-1 3 4
  • GTPase Activating Rap/RanGAP Domain-Like 1 2 3
  • GAP-Related Interacting Protein To E12 2 3
  • RalGAPalpha1 2 3
  • KIAA0884 2 4
  • GARNL1 3 4
  • TULIP1 3 4
  • P240 3 4
  • Ral GTPase Activating Protein, Alpha Subunit 1 (Catalytic) 3
  • Ral GTPase Activating Protein Catalytic Alpha Subunit 1 3
  • GTPase-Activating Rap/Ran-GAP Domain-Like 1 4
  • GTPase Activating RANGAP Domain-Like 1 2
  • GAP-Related-Interacting Partner To E12 4
  • DKFZp667F074 2
  • RALGAPA1 5
  • NEDHRIT 3
  • Tulip1 2

External Ids for RALGAPA1 Gene

Previous HGNC Symbols for RALGAPA1 Gene

  • GARNL1

Previous GeneCards Identifiers for RALGAPA1 Gene

  • GC14M035080
  • GC14M036008
  • GC14M016121

Summaries for RALGAPA1 Gene

Entrez Gene Summary for RALGAPA1 Gene

  • This gene encodes a major subunit of the RAL-GTPase activating protein. A similar protein in mouse binds E12, a transcriptional regulator of immunoglobulin genes. The mouse protein also functions in skeletal muscle by binding to the regulatory 14-3-3 proteins upon stimulation with insulin or muscle contraction. A pseudogene of this gene has been identified on chromosome 9. [provided by RefSeq, Oct 2016]

GeneCards Summary for RALGAPA1 Gene

RALGAPA1 (Ral GTPase Activating Protein Catalytic Subunit Alpha 1) is a Protein Coding gene. Diseases associated with RALGAPA1 include Neurodevelopmental Disorder With Hypotonia, Neonatal Respiratory Insufficiency, And Thermodysregulation and Adult Respiratory Distress Syndrome. Among its related pathways are Integrated Breast Cancer Pathway. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity and GTPase activator activity. An important paralog of this gene is RALGAPA2.

UniProtKB/Swiss-Prot Summary for RALGAPA1 Gene

  • Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB.

Gene Wiki entry for RALGAPA1 Gene

Additional gene information for RALGAPA1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RALGAPA1 Gene

Genomics for RALGAPA1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for RALGAPA1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RALGAPA1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RALGAPA1

Genomic Locations for RALGAPA1 Gene

Latest Assembly
chr14:35,538,352-35,809,304
(GRCh38/hg38)
Size:
270,953 bases
Orientation:
Minus strand

Previous Assembly
chr14:36,007,562-36,278,501
(GRCh37/hg19 by Entrez Gene)
Size:
270,940 bases
Orientation:
Minus strand

chr14:36,007,558-36,278,510
(GRCh37/hg19 by Ensembl)
Size:
270,953 bases
Orientation:
Minus strand

Genomic View for RALGAPA1 Gene

Genes around RALGAPA1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RALGAPA1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RALGAPA1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for RALGAPA1 Gene

Proteins for RALGAPA1 Gene

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  • Protein details for RALGAPA1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6GYQ0-RGPA1_HUMAN
    Recommended name:
    Ral GTPase-activating protein subunit alpha-1
    Protein Accession:
    Q6GYQ0
    Secondary Accessions:
    • A6NMA4
    • B9EK38
    • C5NU19
    • O94960
    • Q6GYP9
    • Q6ZT23
    • Q86YF3
    • Q86YF5
    • Q8ND69

    Protein attributes for RALGAPA1 Gene

    Size:
    2036 amino acids
    Molecular mass:
    229832 Da
    Quaternary structure:
    • Component of the heterodimeric RalGAP1 complex with RALGAPB. Heterodimerization is required for activity. Interacts with the HLH region of TCF3/isoform E12 (By similarity).
    SequenceCaution:
    • Sequence=BAC86772.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for RALGAPA1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RALGAPA1 Gene

Protein Expression for RALGAPA1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for RALGAPA1 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for RALGAPA1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for RALGAPA1 Gene

Domains & Families for RALGAPA1 Gene

Gene Families for RALGAPA1 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for RALGAPA1 Gene

InterPro:
Blocks:
  • Rap/ran-GAP
ProtoNet:

Suggested Antigen Peptide Sequences for RALGAPA1 Gene

GenScript: Design optimal peptide antigens:
  • GARNL1 protein (A0PJ59_HUMAN)
  • p240 (RGPA1_HUMAN)
genes like me logo Genes that share domains with RALGAPA1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for RALGAPA1 Gene

Function for RALGAPA1 Gene

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  6. Cell Lines for research

Molecular function for RALGAPA1 Gene

UniProtKB/Swiss-Prot Function:
Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB.

Phenotypes From GWAS Catalog for RALGAPA1 Gene

Gene Ontology (GO) - Molecular Function for RALGAPA1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005096 GTPase activator activity IBA,ISS --
GO:0046982 protein heterodimerization activity IPI 19520869
genes like me logo Genes that share ontologies with RALGAPA1: view
genes like me logo Genes that share phenotypes with RALGAPA1: view

Human Phenotype Ontology for RALGAPA1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RALGAPA1

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for RALGAPA1 Gene

Localization for RALGAPA1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RALGAPA1 Gene

Cytoplasm. Nucleus. Note=Translocated to the nucleus, when associated with TCF3/E12. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RALGAPA1 gene
Compartment Confidence
nucleus 4
cytosol 3
mitochondrion 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Mitochondria (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RALGAPA1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm IBA,ISS --
genes like me logo Genes that share ontologies with RALGAPA1: view

Pathways & Interactions for RALGAPA1 Gene

PathCards logo

SuperPathways for RALGAPA1 Gene

genes like me logo Genes that share pathways with RALGAPA1: view

Pathways by source for RALGAPA1 Gene

1 BioSystems pathway for RALGAPA1 Gene
1 GeneTex pathway for RALGAPA1 Gene

Gene Ontology (GO) - Biological Process for RALGAPA1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0043547 positive regulation of GTPase activity IEA --
GO:0051056 regulation of small GTPase mediated signal transduction IEA --
GO:0090630 activation of GTPase activity ISS --
genes like me logo Genes that share ontologies with RALGAPA1: view

No data available for SIGNOR curated interactions for RALGAPA1 Gene

Drugs & Compounds for RALGAPA1 Gene

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(1) Drugs for RALGAPA1 Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
RBC8 Pharma 0

(1) ApexBio Compounds for RALGAPA1 Gene

Compound Action Cas Number
RBC8 361185-42-4
genes like me logo Genes that share compounds with RALGAPA1: view

Drug products for research

Transcripts for RALGAPA1 Gene

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mRNA/cDNA for RALGAPA1 Gene

11 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
20 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RALGAPA1

Alternative Splicing Database (ASD) splice patterns (SP) for RALGAPA1 Gene

No ASD Table

Relevant External Links for RALGAPA1 Gene

GeneLoc Exon Structure for
RALGAPA1

Expression for RALGAPA1 Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RALGAPA1 Gene

mRNA expression in normal human tissues for RALGAPA1 Gene
mRNA expression by GTEx for RALGAPA1 GenemRNA expression by BioGPS for RALGAPA1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RALGAPA1 Gene

This gene is overexpressed in Liver (23.4) and Esophagus (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RALGAPA1 Gene



Protein tissue co-expression partners for RALGAPA1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RALGAPA1

SOURCE GeneReport for Unigene cluster for RALGAPA1 Gene:

Hs.113150

mRNA Expression by UniProt/SwissProt for RALGAPA1 Gene:

Q6GYQ0-RGPA1_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for RALGAPA1 Gene

  • Nervous system(4.6)
  • Skin(4.3)
  • Liver(4.3)
  • Lymph node(4.1)
genes like me logo Genes that share expression patterns with RALGAPA1: view

Primer products for research

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RALGAPA1 Gene

Orthologs for RALGAPA1 Gene

This gene was present in the common ancestor of animals.

Orthologs for RALGAPA1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia RALGAPA1 30 31
  • 99.74 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia GARNL1 31
  • 94 (a)
 OneToOne
RALGAPA1 30
  • 93.99 (n)
Rat
(Rattus norvegicus)
 Mammalia Ralgapa1 30
  • 91.08 (n)
Platypus
(Ornithorhynchus anatinus)
 Mammalia RALGAPA1 31
  • 91 (a)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Ralgapa1 30 17 31
  • 90.85 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia RALGAPA1 31
  • 87 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves RALGAPA1 30 31
  • 81.47 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia -- 31
  • 89 (a)
 OneToMany
-- 31
  • 86 (a)
 OneToMany
Zebrafish
(Danio rerio)
 Actinopterygii ralgapa1 30 31
  • 67.68 (n)
 OneToOne
Fruit Fly
(Drosophila melanogaster)
 Insecta CG5521 30 31
  • 48.68 (n)
 OneToMany
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP004143 30
  • 46.9 (n)
Worm
(Caenorhabditis elegans)
 Secernentea Y18H1A.3 31
  • 26 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 42 (a)
 OneToMany
Species where no ortholog for RALGAPA1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for RALGAPA1 Gene

ENSEMBL:
Gene Tree for RALGAPA1 (if available)
TreeFam:
Gene Tree for RALGAPA1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RALGAPA1: view image

Paralogs for RALGAPA1 Gene

Paralogs for RALGAPA1 Gene

(3) SIMAP similar genes for RALGAPA1 Gene using alignment to 4 proteins:

  • RGPA1_HUMAN
  • H0YJ04_HUMAN
  • H0YJB5_HUMAN
  • L8EAR6_HUMAN

Pseudogenes.org Pseudogenes for RALGAPA1 Gene

genes like me logo Genes that share paralogs with RALGAPA1: view

Variants for RALGAPA1 Gene

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  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RALGAPA1 Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
rs142294657 Benign: not provided 35,742,494(-) T/C
NM_014990.3(RALGAPA1):c.1323A>G (p.Gln441=) 		SYNONYMOUS
rs148182075 Benign: not provided 35,808,794(-) G/A
NM_014990.3(RALGAPA1):c.42C>T (p.Thr14=) 		SYNONYMOUS
rs148266372 Benign: not provided 35,677,991(-) T/C
NM_014990.3(RALGAPA1):c.3065A>G (p.Glu1022Gly) 		MISSENSE
rs1555427204 Uncertain Significance: Inborn genetic diseases 35,748,691(-) C/A
NM_001346249.2(RALGAPA1):c.1145G>T (p.Ser382Ile) 		MISSENSE
rs1594642302 Pathogenic: Generalized hypotonia; Respiratory distress; Feeding difficulties; Infantile spasms; Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation 35,572,678(-) G/C
NM_001346249.2(RALGAPA1):c.7250C>G (p.Ser2417Ter) 		NONSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RALGAPA1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RALGAPA1 Gene

Variant ID Type Subtype PubMed ID
esv2549342 CNV deletion 19546169
esv3307851 CNV mobile element insertion 20981092
esv3338357 CNV insertion 20981092
esv3634063 CNV loss 21293372
esv3634066 CNV loss 21293372
nsv1241 CNV insertion 18451855
nsv456206 CNV loss 19166990
nsv507742 OTHER sequence alteration 20534489
nsv525294 CNV loss 19592680
nsv564341 CNV loss 21841781
nsv564342 CNV loss 21841781
nsv564343 CNV loss 21841781
nsv976331 CNV duplication 23825009

Variation tolerance for RALGAPA1 Gene

Residual Variation Intolerance Score: 7.94% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.80; 86.82% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RALGAPA1 Gene

Human Gene Mutation Database (HGMD)
RALGAPA1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RALGAPA1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RALGAPA1 Gene

Disorders for RALGAPA1 Gene

MalaCards: The human disease database

(6) MalaCards diseases for RALGAPA1 Gene - From: OMI, CVR, SWI, COP, and GCD

Disorder Aliases PubMed IDs
neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation
  • nedhrit
adult respiratory distress syndrome
  • acute respiratory distress syndrome
west syndrome
  • epileptic encephalopathy, early infantile, 1
hypotonia
holoprosencephaly 8
  • hpe8
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

RGPA1_HUMAN
  • Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (NEDHRIT) [MIM:618797]: An autosomal recessive disorder characterized by profound neurodevelopmental disability, muscular hypotonia, feeding abnormalities, recurrent fever episodes, infantile spasms, and moderate dysmorphic facial features. Brain imaging shows thin corpus or dysplastic corpus callosum, and additional unspecific abnormalities including gray matter heterotopias, ectopic posterior pituitary, signal abnormalities in basal ganglia, and stratum subependymale. {ECO:0000269 PubMed:32004447}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for RALGAPA1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with RALGAPA1: view

No data available for Genatlas for RALGAPA1 Gene

Publications for RALGAPA1 Gene

  1. Bi-allelic Variants in RALGAPA1 Cause Profound Neurodevelopmental Disability, Muscular Hypotonia, Infantile Spasms, and Feeding Abnormalities. (PMID: 32004447) Wagner M … Distelmaier F (American journal of human genetics 2020) 3 4 74
  2. Tuberous sclerosis tumor suppressor complex-like complexes act as GTPase-activating proteins for Ral GTPases. (PMID: 19520869) Shirakawa R … Horiuchi H (The Journal of biological chemistry 2009) 2 3 4
  3. Cloning, genomic structure, and expression profiles of TULIP1 (GARNL1), a brain-expressed candidate gene for 14q13-linked neurological phenotypes, and its murine homologue. (PMID: 15498464) Schwarzbraun T … Petek E (Genomics 2004) 3 4 23
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4

ExternalLinks

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