AGAP3

protein-coding

ArfGAP with GTPase domain, ankyrin repeat and PH domain 3, the group of Ankyrin repeat domain containing|ArfGAPs|BAR-PH domain containing

Gene summary

This gene encodes an essential component of the N-methyl-D-aspartate (NMDA) receptor signaling complex which mediates long-term potentiation in synapses by linking activation of NMDA receptor to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking. The encoded protein contains an N-terminal GTPase-like domain, a pleckstrin homology domain, an ArfGAP domain and several C-terminal ankryn repeat domains. [provided by RefSeq, Apr 2017]

Previous symbols:

CENTG3

MANE transcript

NM_031946.7

Inheritance

—

ClinVar variants

U:127B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr7:151,085,831-151,144,436

External References & Databases

Ensembl (ENSG00000133612)

Transcript & Mutation Effects

hg38 • Region Span ~58.6 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 AGAP3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031946.7. 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	2 clinvar	1 clinvar	4
missense			121 clinvar	5 clinvar	1 clinvar	127
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar		1 clinvar	2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	127	7	3	137

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031946.7	RefSeq	NP_114152.3	18	MANE Select
ENST00000397238.7	Ensembl	ENSP00000380413.2	18	MANE Select
NM_001042535.4	RefSeq	NP_001036000.1	9	Standard
NM_001281300.2	RefSeq	NP_001268229.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)

Biological Process

obsolete protein import into nucleus, translocation
signal transduction
cellular response to reactive oxygen species
proteasome-mediated ubiquitin-dependent protein catabolic process
positive regulation of GTPase activity

Molecular Function

GTPase activity
GTPase activator activity
GTP binding
polyubiquitin modification-dependent protein binding
metal ion binding

Cellular Component

nucleus
cytoplasm
membrane
cell periphery

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397238
Coding exons: 18
Length: 58606
Individuals with no LoFs: 124782
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 124802
p: 0.0000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.99	377	580	0.650	0.0000394	5845
Missense (PolyPhen)		120	250.13	0.47975		2386
Synonymous	-0.460	265	256	1.04	0.0000180	1941
Loss of Function	4.95	8	43.0	0.186	0.00000232	450

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00021	0.00019	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000049	0.000046	rare
European (Non-Finnish)	0.000072	0.000071	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase-activating protein for the ADP ribosylation factor family (Potential). GTPase which may be involved in the degradation of expanded polyglutamine proteins through the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:16461359, ECO:0000305}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.221
RVIS EVS: -1
RVIS percentile EVS: 8.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.331

Gene Damage Prediction

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