AGAP2

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

Basic information

Region (hg38): 12:57723760-57742157

Previous symbols: [ "CENTG1" ]

Links

ENSG00000135439 ∙ NCBI:116986 ∙ OMIM:605476 ∙ HGNC:16921 ∙ Uniprot:Q99490 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGAP2 gene.

• Inborn genetic diseases (40 variants)
• not provided (4 variants)
• AGAP2-related condition (2 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGAP2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			43			43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	43	1	1

Variants in AGAP2

This is a list of pathogenic ClinVar variants found in the AGAP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-57726635-T-C		not specified	Uncertain significance (May 10, 2022)
12-57726649-G-A		not specified	Uncertain significance (Mar 27, 2023)
12-57726658-G-C		not specified	Uncertain significance (Dec 21, 2022)
12-57726761-C-T		not specified	Uncertain significance (Sep 01, 2021)
12-57727000-C-T		not specified	Uncertain significance (Dec 27, 2022)
12-57727002-T-C		not specified	Uncertain significance (Jun 21, 2022)
12-57727022-G-A		AGAP2-related disorder	Likely benign (Mar 29, 2019)
12-57727112-G-C		not specified	Uncertain significance (Aug 11, 2022)
12-57727149-A-G		not specified	Uncertain significance (Apr 07, 2023)
12-57727170-A-C		not specified	Uncertain significance (Jan 24, 2023)
12-57727427-C-A		not specified	Uncertain significance (Sep 16, 2021)
12-57727471-T-A		not specified	Uncertain significance (Aug 31, 2022)
12-57727704-A-G		not specified	Likely benign (Jan 29, 2024)
12-57727716-T-A		not specified	Uncertain significance (Apr 25, 2023)
12-57727974-A-G		not specified	Uncertain significance (Feb 13, 2024)
12-57728061-A-G		AGAP2-related disorder	Uncertain significance (Oct 07, 2022)
12-57729733-A-G		AGAP2-related disorder	Likely benign (Mar 25, 2019)
12-57730531-T-G		not specified	Uncertain significance (Feb 27, 2023)
12-57730577-G-A		AGAP2-related disorder	Likely benign (Oct 28, 2019)
12-57730609-T-C		not specified	Uncertain significance (Feb 22, 2023)
12-57730883-C-T		not specified	Uncertain significance (Feb 17, 2022)
12-57730932-C-T		not specified	Uncertain significance (Jan 04, 2024)
12-57731596-C-A		not specified	Uncertain significance (Jan 04, 2024)
12-57731844-G-A		not specified	Uncertain significance (Jul 19, 2023)
12-57731880-C-T		not specified	Uncertain significance (Jan 31, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGAP2	protein_coding	protein_coding	ENST00000547588	19	16961

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00184	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.39	401	643	0.624	0.0000369	7467
Missense in Polyphen		129	257.51	0.50096		2807
Synonymous	1.04	252	274	0.920	0.0000158	2642
Loss of Function	5.58	7	49.3	0.142	0.00000292	520

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000206	0.000198
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion. {ECO:0000269|PubMed:12640130, ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15118108, ECO:0000269|PubMed:16079295}.
• Pathway: Endocytosis - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Prolactin Signaling Pathway;JAK-STAT;Developmental Biology;Netrin-1 signaling;Axon guidance;Netrin-mediated signaling events;Trk receptor signaling mediated by PI3K and PLC-gamma (Consensus)

Recessive Scores

• pRec: 0.233

Intolerance Scores

• loftool: 0.494
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.56

Haploinsufficiency Scores

• pHI: 0.817
• hipred: Y
• hipred_score: 0.669
• ghis: 0.599

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.530

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agap2
• Phenotype: liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: protein transport;negative regulation of protein catabolic process;negative regulation of neuron apoptotic process;positive regulation of GTPase activity;positive regulation of 1-phosphatidylinositol-3-kinase activity
• Cellular component: nucleus;nucleolus;cytoplasm;mitochondrion;membrane;extracellular exosome
• Molecular function: GTPase activity;GTPase activator activity;protein binding;GTP binding;metal ion binding