GeneBe

RACGAP1

protein-coding

Rac GTPase activating protein 1

Gene summary

This gene encodes a GTPase-activating protein (GAP) that is a compoment of the centralspindlin complex. This protein binds activated forms of Rho GTPases and stimulates GTP hydrolysis, which results in negative regulation of Rho-mediated signals. This protein plays a regulatory role in cytokinesis, cell growth, and differentiation. Alternatively spliced transcript variants have been found for this gene. There is a pseudogene for this gene on chromosome 12. [provided by RefSeq, Feb 2016]

MANE transcript

NM_001319999.2

Inheritance

AR

ClinVar variants

P:3U:64B:3

Top phenotype

Anemia, congenital dyserythropoietic, type IIIb, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr12:49,976,923-50,033,136

External References & Databases

Ensembl (ENSG00000161800)NCBI Gene (29127)OMIM (604980)HGNC:9804GenCCUniProt (Q9H0H5)AlphaFoldClinVar (RACGAP1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~56.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Anemia, congenital dyserythropoietic, type IIIb, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030711

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Anemia, congenital dyserythropoietic, type IIIb, autosomal recessiveAR

Manifestation: Hematologic

Intervention: Hematologic

Rationale: The condition can involve clincially significant anemia requiring interventions such as blood transfusions, and awareness may allow prompt diagnosis and management

Refs: 34818416; 36200420Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RACGAP1 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 62
not providedTotal: 7
Anemia, congenital dyserythropoietic, type IIIbTotal: 3
Anemia, congenital dyserythropoietic, type IIIb, autosomal recessiveTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001319999.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
1
clinvar
 3
missense
3
clinvar
62
clinvar
1
clinvar
 66
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total30642170

Highest pathogenic variant AF is 0.000004105596

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 105 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001319999.2RefSeqNP_001306928.116MANE Select
ENST00000312377.10EnsemblENSP00000309871.516MANE Select
NM_001126103.3RefSeqNP_001119575.116Standard
NM_001126104.3RefSeqNP_001119576.116Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
racgap1Danio rerio

Structure: neutrophil

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Signal Transduction of S1P Receptor
  • Wnt Signaling Pathway and Pluripotency
  • Signal Transduction
  • Vesicle-mediated transport
  • Membrane Trafficking

Biological Process

  • mitotic cytokinesis
  • actomyosin contractile ring assembly
  • retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
  • microtubule-based movement
  • spermatogenesis

Molecular Function

  • GTPase activator activity
  • protein binding
  • phosphatidylinositol-3,4,5-trisphosphate binding
  • microtubule binding
  • protein kinase binding

Cellular Component

  • acrosomal vesicle
  • nucleus
  • nucleoplasm
  • cytosol
  • microtubule

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000434422
Coding exons
16
Length
56214
Individuals with no LoFs
125704
Homozygous LoFs
0
Heterozygous LoFs
44
Defined
125748
p
0.000175
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.012483540.7000.00001924151
Missense (PolyPhen)5295.4160.544981219
Synonymous0.3491151200.9590.000005651240
Loss of Function3.851237.40.3210.00000233388

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American00.0absent
Ashkenazi Jewish0.000300.00030rare
East Asian0.000330.00033rare
Finnish0.000550.00055rare
European (Non-Finnish)0.000120.00012rare
South Asian0.000160.00016rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity. Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}.;

Recessive Scores

pRec
0.159

Intolerance Scores

LoFtool
0.472
RVIS EVS
-0.4
RVIS percentile EVS
26.73

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.781

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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