AGAP1

protein-coding

ArfGAP with GTPase domain, ankyrin repeat and PH domain 1, the group of ArfGAPs|BAR-PH domain containing|Ankyrin repeat domain containing

Gene summary

This gene encodes a member of an ADP-ribosylation factor GTPase-activating protein family involved in membrane trafficking and cytoskeleton dynamics. This gene functions as a direct regulator of the adaptor-related protein complex 3 on endosomes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Previous symbols:

CENTG2

MANE transcript

NM_001037131.3

Inheritance

ClinVar variants

U:217B:107

Top phenotype

AGAP1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr2:235,494,043-236,131,793

External References & Databases

Ensembl (ENSG00000157985)

Transcript & Mutation Effects

hg38 • Region Span ~637.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebral palsyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0006497

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGAP1 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 265

not specifiedTotal: 137

AGAP1-related disorderTotal: 2

AGAP1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001037131.3. 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			1 clinvar	81 clinvar	16 clinvar	98
missense			207 clinvar	8 clinvar	2 clinvar	217
nonsense			1 clinvar			1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	217	89	18	324

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001037131.3	RefSeq	NP_001032208.1	18	MANE Select
ENST00000304032.13	Ensembl	ENSP00000307634.7	18	MANE Select
NM_001244888.2	RefSeq	NP_001231817.1	10	Standard
NM_001436125.1	RefSeq	NP_001423054.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)

Biological Process

protein transport
positive regulation of GTPase activity

Molecular Function

GTPase activity
GTPase activator activity
GTP binding
phospholipid binding
metal ion binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304032
Coding exons: 18
Length: 637712
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.29	481	567	0.848	0.0000377	5588
Missense (PolyPhen)		219	264.65	0.82752		2833
Synonymous	-1.64	283	250	1.13	0.0000190	1723
Loss of Function	5.86	6	51.3	0.117	0.00000313	480

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system. {ECO:0000269|PubMed:12640130}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.315
RVIS EVS: -2.39
RVIS percentile EVS: 1.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.365

Gene Damage Prediction

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