ARAP1

protein-coding

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1, the group of Sterile alpha motif domain containing|ArfGAPs|Ankyrin repeat domain containing|Pleckstrin homology domain containing

Gene summary

The protein encoded by this gene contains SAM, ARF-GAP, RHO-GAP, ankyrin repeat, RAS-associating, and pleckstrin homology (PH) domains. In vitro, this protein displays RHO-GAP and phosphatidylinositol (3,4,5) trisphosphate (PIP3)-dependent ARF-GAP activity. The encoded protein associates with the Golgi, and the ARF-GAP activity mediates changes in the Golgi and the formation of filopodia. It is thought to regulate the cell-specific trafficking of a receptor protein involved in apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

Previous symbols:

CENTD2

MANE transcript

NM_001040118.3

Inheritance

—

ClinVar variants

U:269B:13

Top phenotype

Autism

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr11:72,685,069-72,793,599

External References & Databases

Ensembl (ENSG00000186635)

Transcript & Mutation Effects

hg38 • Region Span ~108.5 kb

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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 ARAP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 243

not providedTotal: 8

AutismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040118.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	1 clinvar	2 clinvar	10
missense			247 clinvar	8 clinvar	2 clinvar	257
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	269	9	4	282

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040118.3	RefSeq	NP_001035207.1	33	MANE Select
ENST00000393609.8	Ensembl	ENSP00000377233.3	33	MANE Select
NM_001135190.2	RefSeq	NP_001128662.1	29	Standard
NM_001369489.1	RefSeq	NP_001356418.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Signaling by PTK6
Signal Transduction
rho cell motility signaling pathway
t cell receptor signaling pathway

Biological Process

positive regulation of receptor recycling
signal transduction
regulation of cell shape
actin filament reorganization involved in cell cycle
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding
phosphatidylinositol-3,4,5-trisphosphate binding
type 1 angiotensin receptor binding
metal ion binding

Cellular Component

nucleoplasm
Golgi apparatus
trans-Golgi network
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393609
Coding exons: 33
Length: 108531
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.14	729	910	0.801	0.0000623	9228
Missense (PolyPhen)		224	328.42	0.68206		3351
Synonymous	0.977	350	374	0.936	0.0000252	2987
Loss of Function	6.14	18	75.7	0.238	0.00000389	833

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00020	0.00020	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Has a preference for ARF1 and ARF5 (By similarity). {ECO:0000250, ECO:0000269|PubMed:11804590}.;

Recessive Scores

pRec: 0.174

Intolerance Scores

LoFtool: 0.775
RVIS EVS: -1.45
RVIS percentile EVS: 3.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.866

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium