AGFG2

Summary

AGFG2 (ArfGAP with FG repeats 2, HGNC:5177) is a protein-coding gene on chromosome 7q22.1, encoding Arf-GAP domain and FG repeat-containing protein 2 (O95081).

This gene is a member of the HIV-1 Rev binding protein (HRB) family and encodes a protein with one Arf-GAP zinc finger domain, several phe-gly (FG) motifs, and four asn-pro-phe (NPF) motifs. This protein interacts with Eps15 homology (EH) domains and plays a role in the Rev export pathway, which mediates the nucleocytoplasmic transfer of proteins and RNAs. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Source: NCBI Gene 3268 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_006076

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5177
Approved symbol	AGFG2
Name	ArfGAP with FG repeats 2
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RABR
Ensembl gene	ENSG00000106351
Ensembl biotype	protein_coding
OMIM	604019
Entrez	3268

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000300176, ENST00000429987, ENST00000430857, ENST00000474713, ENST00000477022, ENST00000875429, ENST00000875430, ENST00000875431, ENST00000875432, ENST00000875433, ENST00000875434, ENST00000875435, ENST00000875436, ENST00000967112

RefSeq mRNA: 1 — MANE Select: NM_006076 NM_006076

CCDS: CCDS5697

Canonical transcript exons

ENST00000300176 — 12 exons

Exon	Start	End
ENSE00001350364	100564932	100568220
ENSE00001907642	100539203	100539567
ENSE00003461857	100553347	100553500
ENSE00003522960	100562863	100562946
ENSE00003580867	100564218	100564303
ENSE00003615555	100548822	100548915
ENSE00003622739	100562594	100562682
ENSE00003636936	100563834	100563962
ENSE00003657495	100555610	100555735
ENSE00003657846	100554093	100554258
ENSE00003669905	100562259	100562379
ENSE00003679922	100550396	100550511

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0695 / max 251.0870, expressed in 1703 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79997	9.2073	1667
79996	0.9177	493
80007	0.6772	316
79999	0.1618	73
79998	0.0864	30
80003	0.0192	7

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	97.75	gold quality
right adrenal gland cortex	UBERON:0035827	95.95	gold quality
right adrenal gland	UBERON:0001233	95.52	gold quality
left adrenal gland	UBERON:0001234	94.67	gold quality
right ovary	UBERON:0002118	94.61	gold quality
left adrenal gland cortex	UBERON:0035825	94.31	gold quality
left ovary	UBERON:0002119	94.29	gold quality
right lobe of liver	UBERON:0001114	94.20	gold quality
mucosa of transverse colon	UBERON:0004991	94.04	gold quality
saliva-secreting gland	UBERON:0001044	94.02	gold quality
minor salivary gland	UBERON:0001830	93.00	gold quality
adrenal cortex	UBERON:0001235	92.57	gold quality
metanephros cortex	UBERON:0010533	91.96	gold quality
adrenal gland	UBERON:0002369	91.77	gold quality
body of uterus	UBERON:0009853	91.65	gold quality
lower esophagus mucosa	UBERON:0035834	90.67	gold quality
left uterine tube	UBERON:0001303	90.27	gold quality
adenohypophysis	UBERON:0002196	90.07	gold quality
ovary	UBERON:0000992	89.89	gold quality
lower esophagus	UBERON:0013473	89.80	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.79	gold quality
transverse colon	UBERON:0001157	89.77	gold quality
spleen	UBERON:0002106	89.56	gold quality
mouth mucosa	UBERON:0003729	89.54	gold quality
mucosa of stomach	UBERON:0001199	89.39	gold quality
skin of leg	UBERON:0001511	89.35	gold quality
esophagus	UBERON:0001043	89.14	gold quality
granulocyte	CL:0000094	89.02	gold quality
descending thoracic aorta	UBERON:0002345	89.00	gold quality
body of pancreas	UBERON:0001150	88.97	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1

miRNA regulators (miRDB)

113 targeting AGFG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-221-5P	99.86	65.45	1052

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	agfg2	ENSDARG00000069334
mus_musculus	Agfg2	ENSMUSG00000029722
rattus_norvegicus	Agfg2	ENSRNOG00000001404

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), ACAP3 (ENSG00000131584), AGAP3 (ENSG00000133612), AGAP2 (ENSG00000135439), APPL2 (ENSG00000136044), GIT2 (ENSG00000139436), ARFGAP2 (ENSG00000149182), ASAP2 (ENSG00000151693), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP domain and FG repeat-containing protein 2 — O95081 (reviewed: O95081)

Alternative names: HIV-1 Rev-binding protein-like protein, Rev/Rex activation domain-binding protein related

All UniProt accessions (4): O95081, A0A0C4DG34, A4D2D6, H7BZA5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with EPS15R.

Domain organisation. Contains FG repeats and 4 N-P-F repeats.

Isoforms (2)

UniProt ID	Names	Canonical?
O95081-1	1	yes
O95081-2	2

RefSeq proteins (1): NP_006067* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR052248	Arf-GAP_FG-repeat_protein	Family

Pfam: PF01412

UniProt features (18 total): sequence conflict 4, compositionally biased region 4, region of interest 3, splice variant 2, chain 1, domain 1, modified residue 1, sequence variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95081-F1	59.26	0.23

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 173

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 181 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, AHRARNT_01, E2F_Q4_01, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MALE_GAMETE_GENERATION, TCF4_Q5, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, MARTINEZ_RB1_TARGETS_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_NUCLEUS_ORGANIZATION

GO Biological Process (3): acrosome assembly (GO:0001675), spermatid nucleus differentiation (GO:0007289), intermediate filament organization (GO:0045109)

GO Molecular Function (3): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
spermatid development	2
cellular anatomical structure	2
developmental process involved in reproduction	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
nucleus organization	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGFG2	EPS15L1	Q9UBC2	829
AGFG2	EPS15	P42566	602
AGFG2	ACAP1	Q15027	577
AGFG2	RANBP6	O60518	556
AGFG2	MRPL46	Q9H2W6	544
AGFG2	TIMM10B	Q9Y5J6	543
AGFG2	MRPS5	P82675	511
AGFG2	NUMBL	Q9Y6R0	491
AGFG2	DARS2	Q6PI48	490
AGFG2	KIF16B	Q96L93	476
AGFG2	ASAP2	O43150	461
AGFG2	DAB2	P98082	459
AGFG2	RPL14	P50914	457
AGFG2	PSMB4	P28070	456
AGFG2	ITSN1	Q15811	456
AGFG2	ANKRD46	Q86W74	456

IntAct

5 interactions, top by confidence:

A	B	Type	Score
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
AGFG2	AGFG1	psi-mi:“MI:0914”(association)	0.350
AGFG2	lcrS	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): AGFG2 (Phenotypic Enhancement), AGFG2 (Phenotypic Enhancement), EPS15 (Co-fractionation), AGFG2 (Affinity Capture-MS), STARD7 (Affinity Capture-MS), AGFG1 (Affinity Capture-MS), TRIM68 (Affinity Capture-MS), AGFG2 (Affinity Capture-RNA), AGFG2 (Affinity Capture-MS), AGFG2 (Proximity Label-MS), AGFG2 (Proximity Label-MS), AGFG2 (Affinity Capture-RNA), AGFG2 (Proximity Label-MS), AGFG2 (Affinity Capture-MS), AGFG2 (Protein-peptide)

ESM2 similar proteins: A0JME2, A5H447, A6NF01, A8CG34, E9Q3G8, F4ID16, G0SDP9, G5E8Z2, O08587, O15504, O88797, O95081, P20676, P49790, P49791, P52591, P52594, P98082, Q03173, Q0VA45, Q2TA45, Q4KLH5, Q5FVW4, Q5PRE5, Q5RB98, Q5SV85, Q5XGN1, Q5ZI22, Q5ZIE8, Q5ZM88, Q64028, Q640Z6, Q6P0U9, Q80WC7, Q86XN7, Q8CIC2, Q8K2K6, Q8K3Z9, Q8L7F7, Q8R080

Diamond homologs: O95081, P52594, Q2TA45, Q4KLH5, Q54DK4, Q80WC7, Q8K2K6, Q8RXE7, A1L520, O94601, Q09531, Q17R07, Q3MID3, Q4KLN7, Q4R4C9, Q5R787, Q5RAT7, Q8N6H7, Q99K28, Q9D8S3, Q9NP61, O00418, O01991, O08796, P42527, P70531, P90648, Q54SF9, Q6B9X6, Q8MY12, Q923J1, Q925B3, Q96QP1, Q96QT4, Q9CXB8, Q9FL69, Q8IYB5, O75689, O80925, P32572

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

84 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1874 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100539564:TCCT:T	donor_gain	1.0000
7:100539565:CCTG:C	donor_loss	1.0000
7:100539567:TGTG:T	donor_loss	1.0000
7:100539568:G:C	donor_loss	1.0000
7:100539568:G:GG	donor_gain	1.0000
7:100539569:T:A	donor_loss	1.0000
7:100539583:G:GT	donor_gain	1.0000
7:100545552:GCT:G	donor_gain	1.0000
7:100548806:T:A	acceptor_gain	1.0000
7:100548817:CATA:C	acceptor_loss	1.0000
7:100548819:T:G	acceptor_gain	1.0000
7:100548819:TA:T	acceptor_loss	1.0000
7:100548820:A:AG	acceptor_gain	1.0000
7:100548820:A:AT	acceptor_loss	1.0000
7:100548821:G:GC	acceptor_loss	1.0000
7:100548821:G:GG	acceptor_gain	1.0000
7:100548821:GGA:G	acceptor_gain	1.0000
7:100548821:GGAGA:G	acceptor_gain	1.0000
7:100550508:GATG:G	donor_gain	1.0000
7:100550512:G:GG	donor_gain	1.0000
7:100554090:A:AG	acceptor_gain	1.0000
7:100554091:A:G	acceptor_gain	1.0000
7:100554092:GCCC:G	acceptor_gain	1.0000
7:100554255:GGGG:G	donor_gain	1.0000
7:100554256:GGGG:G	donor_gain	1.0000
7:100555607:CA:C	acceptor_loss	1.0000
7:100555608:A:AG	acceptor_gain	1.0000
7:100555609:G:GG	acceptor_gain	1.0000
7:100555609:G:GT	acceptor_loss	1.0000
7:100555609:GGCCA:G	acceptor_gain	1.0000

AlphaMissense

3102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100539485:T:C	C47R	1.000
7:100539486:G:A	C47Y	1.000
7:100539487:C:G	C47W	1.000
7:100539494:T:C	C50R	1.000
7:100539515:T:C	Y57H	1.000
7:100539533:G:C	G63R	1.000
7:100539534:G:A	G63D	1.000
7:100539545:T:A	C67S	1.000
7:100539545:T:C	C67R	1.000
7:100539546:G:A	C67Y	1.000
7:100539546:G:C	C67S	1.000
7:100539546:G:T	C67F	1.000
7:100539547:C:G	C67W	1.000
7:100539554:T:C	C70R	1.000
7:100539555:G:A	C70Y	1.000
7:100539556:C:G	C70W	1.000
7:100539558:C:T	S71F	1.000
7:100539561:G:A	G72D	1.000
7:100539567:T:C	L74P	1.000
7:100548824:G:C	R75T	1.000
7:100548824:G:T	R75I	1.000
7:100548825:A:C	R75S	1.000
7:100548825:A:T	R75S	1.000
7:100548844:C:A	R82S	1.000
7:100548848:T:A	V83D	1.000
7:100548850:A:G	K84E	1.000
7:100548851:A:T	K84M	1.000
7:100548852:G:C	K84N	1.000
7:100548852:G:T	K84N	1.000
7:100548857:T:A	I86N	1.000

dbSNP variants (sampled 300 via entrez): RS1000191479 (7:100555006 C>G,T), RS1000359324 (7:100549606 C>T), RS1000365981 (7:100547065 G>C), RS1000387614 (7:100563592 C>T), RS1000503582 (7:100568173 T>C), RS1000537371 (7:100568400 C>T), RS1000765206 (7:100562722 G>A), RS1000789568 (7:100541522 A>C), RS1000790168 (7:100554493 C>T), RS1001243019 (7:100542254 G>T), RS1001298171 (7:100548599 C>T), RS1001364753 (7:100555746 C>T), RS1001426701 (7:100541150 T>C), RS1001441754 (7:100562010 C>T), RS1001545306 (7:100566363 C>A,T)

Disease associations

OMIM: gene MIM:604019 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004604_121	Hematocrit	1.000000e-14
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Acetaminophen	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol A	affects expression	1
trichostatin A	affects expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	affects methylation	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.