ASAP2

protein-coding

ArfGAP with SH3 domain, ankyrin repeat and PH domain 2, the group of Ankyrin repeat domain containing|BAR-PH domain containing|ArfGAPs

Gene summary

This gene encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. The protein localizes in the Golgi apparatus and at the plasma membrane, where it colocalizes with protein tyrosine kinase 2-beta (PYK2). The encoded protein forms a stable complex with PYK2 in vivo. This interaction appears to be mediated by binding of its SH3 domain to the C-terminal proline-rich domain of PYK2. The encoded protein is tyrosine phosphorylated by activated PYK2. It has catalytic activity for class I and II ArfGAPs in vitro, and can bind the class III Arf ARF6 without immediate GAP activity. The encoded protein is believed to function as an ARF GAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

Previous symbols:
  • DDEF2

MANE transcript

NM_003887.3

Inheritance

—

ClinVar variants

U:159B:8

Top phenotype

ASAP2-related condition

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr2:9,206,765-9,405,683

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~198.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASAP2 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 138
not providedTotal: 7
ASAP2-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003887.3. 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
4
clinvar
1
clinvar
3
clinvar
8
missense
141
clinvar
3
clinvar
1
clinvar
145
nonsense
4
clinvar
4
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
10
clinvar
10
Total0015944167
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003887.3RefSeqNP_003878.128MANE Select
ENST00000281419.8EnsemblENSP00000281419.328MANE Select
NM_001135191.2RefSeqNP_001128663.127Standard
ENST00000315273.4EnsemblENSP00000316404.427Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Fc gamma R-mediated phagocytosis - Homo sapiens (human)
  • Endocytosis - Homo sapiens (human)
  • Vitamin D Receptor Pathway
  • rho cell motility signaling pathway
  • t cell receptor signaling pathway

Biological Process

  • positive regulation of GTPase activity

Molecular Function

  • GTPase activator activity
  • protein binding
  • metal ion binding

Cellular Component

  • plasma membrane
  • Golgi cisterna membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000281419
Coding exons
28
Length
198919
Individuals with no LoFs
125729
Homozygous LoFs
0
Heterozygous LoFs
19
Defined
125748
p
0.0000756
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.374295910.7260.00003506595
Missense (PolyPhen)112223.580.500942616
Synonymous0.4372392480.9650.00001731901
Loss of Function6.32759.70.1170.00000320677

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.0000560.000054rare
Finnish00.0absent
European (Non-Finnish)0.000120.00011rare
South Asian0.0000660.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Activates the small GTPases ARF1, ARF5 and ARF6. Regulates the formation of post-Golgi vesicles and modulates constitutive secretion. Modulates phagocytosis mediated by Fc gamma receptor and ARF6. Modulates PXN recruitment to focal contacts and cell migration. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:10749932, ECO:0000269|PubMed:11304556}.;

Recessive Scores

pRec
0.112

Intolerance Scores

LoFtool
0.355
RVIS EVS
-1.26
RVIS percentile EVS
5.31

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.784

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerHighMediumHigh
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.