ARFGAP1

Summary

ARFGAP1 (ARF GTPase activating protein 1, HGNC:15852) is a protein-coding gene on chromosome 20q13.33, encoding ADP-ribosylation factor GTPase-activating protein 1 (Q8N6T3). GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1).

The protein encoded by this gene is a GTPase-activating protein, which associates with the Golgi apparatus and which interacts with ADP-ribosylation factor 1. The encoded protein promotes hydrolysis of ADP-ribosylation factor 1-bound GTP and is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. The activity of this protein is stimulated by phosphoinosides and inhibited by phosphatidylcholine. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55738 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 124 total — 10 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018209

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15852
Approved symbol	ARFGAP1
Name	ARF GTPase activating protein 1
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10767, bA261N11.3
Ensembl gene	ENSG00000101199
Ensembl biotype	protein_coding
OMIM	608377
Entrez	55738

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 32 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000353546, ENST00000370275, ENST00000370283, ENST00000395285, ENST00000468975, ENST00000518601, ENST00000518618, ENST00000518691, ENST00000518794, ENST00000519273, ENST00000519531, ENST00000519604, ENST00000520022, ENST00000520485, ENST00000522403, ENST00000522959, ENST00000523114, ENST00000523460, ENST00000524192, ENST00000547204, ENST00000549047, ENST00000549076, ENST00000550188, ENST00000906860, ENST00000906861, ENST00000906862, ENST00000906863, ENST00000906864, ENST00000906865, ENST00000906866, ENST00000906867, ENST00000906868, ENST00000906869, ENST00000940137, ENST00000940138, ENST00000940139, ENST00000940140, ENST00000940141, ENST00000940142, ENST00000940143, ENST00000946862, ENST00000946863

RefSeq mRNA: 5 — MANE Select: NM_018209 NM_001281482, NM_001281483, NM_001281484, NM_018209, NM_175609

CCDS: CCDS13515, CCDS13516, CCDS63326, CCDS63327, CCDS63328

Canonical transcript exons

ENST00000370283 — 13 exons

Exon	Start	End
ENSE00001672623	63287564	63289790
ENSE00002090975	63272813	63272920
ENSE00003460091	63276091	63276200
ENSE00003466526	63281291	63281347
ENSE00003501846	63282819	63282851
ENSE00003534706	63278117	63278203
ENSE00003555177	63285654	63285713
ENSE00003556649	63276480	63276651
ENSE00003568649	63278899	63278995
ENSE00003601123	63277205	63277305
ENSE00003615467	63286366	63286442
ENSE00003619798	63284866	63284922
ENSE00003677317	63275577	63275640

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.1814 / max 39.7286, expressed in 1253 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185800	32.4527	1816
185801	1.8470	1120
185803	0.2462	102
185804	0.0665	23
185805	0.0132	6
185802	0.0086	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	98.76	gold quality
pituitary gland	UBERON:0000007	98.30	gold quality
mucosa of stomach	UBERON:0001199	97.74	gold quality
stromal cell of endometrium	CL:0002255	97.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.05	gold quality
right uterine tube	UBERON:0001302	97.02	gold quality
right lobe of thyroid gland	UBERON:0001119	96.87	gold quality
body of uterus	UBERON:0009853	96.76	gold quality
cerebellar hemisphere	UBERON:0002245	96.71	gold quality
endocervix	UBERON:0000458	96.70	gold quality
metanephros cortex	UBERON:0010533	96.62	gold quality
left lobe of thyroid gland	UBERON:0001120	96.54	gold quality
right ovary	UBERON:0002118	96.54	gold quality
cerebellar cortex	UBERON:0002129	96.54	gold quality
left ovary	UBERON:0002119	96.46	gold quality
body of pancreas	UBERON:0001150	96.37	gold quality
tibial nerve	UBERON:0001323	96.37	gold quality
left uterine tube	UBERON:0001303	96.32	gold quality
right frontal lobe	UBERON:0002810	96.27	gold quality
apex of heart	UBERON:0002098	96.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.80	gold quality
body of stomach	UBERON:0001161	95.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.75	gold quality
minor salivary gland	UBERON:0001830	95.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.71	gold quality
lower esophagus	UBERON:0013473	95.69	gold quality
thyroid gland	UBERON:0002046	95.50	gold quality
granulocyte	CL:0000094	95.45	gold quality
cerebellum	UBERON:0002037	95.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting ARFGAP1, 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-4533	100.00	69.48	2758
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-92B-5P	99.36	63.29	110
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-7843-5P	98.12	65.26	1421
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-6879-5P	97.77	65.52	1521
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-4430	97.47	65.61	1813

Literature-anchored findings (GeneRIF, showing 15)

• The small GTPases of the Ras superfamily mediate numerous biological processes through their ability to cycle between an inactive GDP-bound and an active GTP-bound form. (PMID:15246431)
• ArfGAP1 interacts with the Golgi through multiple hydrophobic motifs and that alternative modes of interaction may exist in tissue-specific ArfGAP1 isoforms. (PMID:16316994)
• SMAP2 functions in the retrograde, early endosome-to-trans golig network pathway in a clathrin- and AP-1-dependent manner. (PMID:16571680)
• coatomer is an allosteric regulator of Arf GAP1 (PMID:18541532)
• Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking (PMID:19015319)
• catalytic amounts of Arf1GAP1 significantly reduce the yield of purified COPI vesicles (PMID:19055691)
• ArfGAP1, ArfGAP2, and ArfGAP3 have overlapping roles in regulating COPI function in Golgi-to-ER retrograde transport. (PMID:19299515)
• role of ARFGAP1 in AP-2-regulated endocytosis has mechanistic parallels with its roles in COPI transport, as both its GAP activity and coat function contribute to promoting AP-2 transport (PMID:21499258)
• ArfGAP1 is identified as the first GTPase activating protein (GAP) for leucine-rich repeat kinase 2 (LRRK2). (PMID:22423108)
• ARFGAP1 is a host factor for Hepatitis C Virus RNA replication, and is hijacked by HCV NS5A to remove COPI cargo Sac1 from the site of HCV replication to maintain high levels of PI4P. (PMID:24623438)
• ARFGAP1 is found associated with lipid droplets at steady state in some but not all hepatocytes. (PMID:25397679)
• ArfGAP1 restricts Mycobacterium tuberculosis entry by controlling the actin cytoskeleton. (PMID:29141986)
• ArfGAP1 acts as a GTPase-activating protein for human ADP-ribosylation factor-like 1 protein. (PMID:33715220)
• ArfGAP1 inhibits mTORC1 lysosomal localization and activation. (PMID:33988249)
• C9orf72 Toxic Species Affect ArfGAP-1 Function. (PMID:37566088)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arfgap1	ENSDARG00000101616
mus_musculus	Arfgap1	ENSMUSG00000027575
drosophila_melanogaster	ArfGAP1	FBGN0020655
caenorhabditis_elegans	K02B12.7	WBGENE00010500

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), 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

ADP-ribosylation factor GTPase-activating protein 1 — Q8N6T3 (reviewed: Q8N6T3)

Alternative names: ADP-ribosylation factor 1 GTPase-activating protein, ARF1-directed GTPase-activating protein

All UniProt accessions (10): Q8N6T3, E5RGL6, E5RHC5, E5RHH7, E5RHT6, E5RIU2, F8VWB3, F8VWH9, F8W1U7, H0YIQ0

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein (GAP) for the ADP ribosylation factor 1 (ARF1). Involved in membrane trafficking and /or vesicle transport. Promotes hydrolysis of the ARF1-bound GTP and thus, is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles, a prerequisite for vesicle’s fusion with target compartment. Probably regulates ARF1-mediated transport via its interaction with the KDELR proteins and TMED2. Overexpression induces the redistribution of the entire Golgi complex to the endoplasmic reticulum, as when ARF1 is deactivated. Its activity is stimulated by phosphoinosides and inhibited by phosphatidylcholine.

Subunit / interactions. Interacts with ARF1. Interacts with the COPI coat proteins, KDELR1 and TMED2. The interaction with TMED2 inhibits the GAP activity.

Subcellular location. Cytoplasm. Golgi apparatus.

Domain organisation. The region downstream of Arf-GAP domain is essential to GAP activity in vivo. This region may be required for its targeting to Golgi membranes.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8N6T3-1	1	yes
Q8N6T3-2	2
Q8N6T3-3	3
Q8N6T3-4	4
Q8N6T3-5	5

RefSeq proteins (5): NP_001268411, NP_001268412, NP_001268413, NP_060679, NP_783202 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily

Pfam: PF01412

UniProt features (42 total): modified residue 13, splice variant 6, helix 6, turn 4, strand 3, compositionally biased region 3, sequence conflict 2, chain 1, domain 1, zinc finger region 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3DWD	X-RAY DIFFRACTION	2.4
3O47	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6T3-F1	61.90	0.32

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 (13): 231, 246, 304, 343, 346, 348, 350, 361, 363, 378, 135, 150, 189

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-2262752	Cellular responses to stress
R-HSA-381070	IRE1alpha activates chaperones
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport
R-HSA-8953897	Cellular responses to stimuli
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 115 (showing top): REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GCM_GSPT1, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, BLALOCK_ALZHEIMERS_DISEASE_UP, LIAO_METASTASIS, GOBP_REGULATION_OF_ENDOCYTOSIS, GCM_NF2, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, KEGG_ENDOCYTOSIS, GOBP_REGULATION_OF_TRANSPORT, GOBP_IMPORT_INTO_CELL, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (4): protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), regulation of endocytosis (GO:0030100), regulation of ARF protein signal transduction (GO:0032012)

GO Molecular Function (4): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): Golgi membrane (GO:0000139), cytosol (GO:0005829), synapse (GO:0045202), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Membrane Trafficking	3
IRE1alpha activates chaperones	1
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
Post-translational protein modification	1
Metabolism of proteins	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cytoplasm	2
cellular anatomical structure	2
intracellular protein localization	1
establishment of protein localization	1
cellular process	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
ARF protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
cell junction	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARFGAP1	ARF1	P10947	930
ARFGAP1	MOGS	Q13724	896
ARFGAP1	RAC2	P15153	651
ARFGAP1	ARF6	P26438	615
ARFGAP1	ARL1	P40616	534
ARFGAP1	GBF1	Q92538	531
ARFGAP1	ARF5	P26437	445
ARFGAP1	EIPR1	Q53HC9	434
ARFGAP1	COPB2	P35606	424
ARFGAP1	RASA1	P20936	399
ARFGAP1	UNC50	Q53HI1	398
ARFGAP1	COPB1	P53618	373
ARFGAP1	PSD	A5PKW4	364
ARFGAP1	GOLPH3	Q9H4A6	357
ARFGAP1	GGA3	Q9NZ52	348

IntAct

77 interactions, top by confidence:

A	B	Type	Score
GSTM5	GSTM3	psi-mi:“MI:0914”(association)	0.830
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ARFGAP1	GRN	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.560
GABARAPL2	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.560
ARFGAP1	FOS	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-2	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP3-2	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.560
GRN	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.560
FOS	ARFGAP1	psi-mi:“MI:0915”(physical association)	0.560
ARFGAP1	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.560
ARFGAP1	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
ARFGAP1	GABARAPL2	psi-mi:“MI:0915”(physical association)	0.560
ARFGAP1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.550
LRRK2	ARFGAP1	psi-mi:“MI:0403”(colocalization)	0.550
ARFGAP1	AURKA	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
Oprm1	Pld2	psi-mi:“MI:0914”(association)	0.480

BioGRID (188): ARFGAP1 (Two-hybrid), ARFGAP1 (Two-hybrid), ARFGAP1 (Two-hybrid), ARFGAP1 (Two-hybrid), KRTAP3-2 (Two-hybrid), KRTAP9-2 (Two-hybrid), KRTAP10-9 (Two-hybrid), ARFGAP1 (Affinity Capture-MS), ARFGAP1 (Affinity Capture-MS), ARFGAP1 (Affinity Capture-MS), ARFGAP1 (Co-fractionation), ARFGAP1 (Co-fractionation), ARFGAP1 (Co-fractionation), ARFGAP1 (Co-fractionation), ARFGAP1 (Co-fractionation)

ESM2 similar proteins: A1L520, A5DDB7, A8WSQ9, O80925, O82171, O94601, P03197, P0C717, P35197, P38682, P53604, P93755, Q09237, Q09446, Q09531, Q0CGL5, Q0WQ57, Q10367, Q17R07, Q20374, Q24546, Q28CM8, Q3KST5, Q3MID3, Q4KLN7, Q4KMC9, Q4R4C9, Q5R787, Q5RAT7, Q62848, Q80Y56, Q8GWI5, Q8H100, Q8N6H7, Q8N6T3, Q95XU6, Q95Y36, Q99K28, Q9C950, Q9D8S3

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q2TA45, Q3MID3, Q3UHD9, Q4KLH5, Q4KLN7, Q4LDD4, Q4R4C9, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ARFGAP1	up-regulates	LRRK2	binding
LRRK2	down-regulates	ARFGAP1	phosphorylation
(2S)-2-[[2-(2,3-dihydro-1H-inden-5-yloxy)-9-[(4-phenylphenyl)methyl]-6-purinyl]amino]-3-phenyl-1-propanol	“down-regulates activity”	ARFGAP1	“chemical inhibition”
ARFGAP1	“up-regulates activity”	ARF1	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by FGFR1 in disease	5	24.8×	8e-05
Cargo recognition for clathrin-mediated endocytosis	5	8.9×	2e-03
RAF/MAP kinase cascade	6	6.2×	3e-03
Vesicle-mediated transport	9	5.3×	7e-04
Signaling by Receptor Tyrosine Kinases	6	5.3×	7e-03
Membrane Trafficking	8	5.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	1
Uncertain significance	82
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1047899	GRCh37/hg19 20q13.33(chr20:61510452-62315381)	Pathogenic
1526700	GRCh37/hg19 20q13.33(chr20:61797521-62318983)	Pathogenic
2427488	NC_000020.10:g.(?61471874)(62078210_?)del	Pathogenic
253468	GRCh37/hg19 20q13.33(chr20:61429900-62293991)x1	Pathogenic
2579288	GRCh38/hg38 20q13.33(chr20:62632017-63794804)x1	Pathogenic
3062402	GRCh37/hg19 20q13.33(chr20:61421505-62070966)x1	Pathogenic
3062407	GRCh37/hg19 20q13.33(chr20:61716119-62416074)x1	Pathogenic
3391940	GRCh37/hg19 20q13.33(chr20:61602951-62070966)x1	Pathogenic
395261	GRCh37/hg19 20q13.33(chr20:61827144-62907467)x1	Pathogenic
58977	GRCh38/hg38 20q13.33(chr20:63095686-63524980)x1	Pathogenic
1341868	NC_000020.11:g.63255263_63498365del	Likely pathogenic

SpliceAI

2964 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63275572:TGCA:T	acceptor_loss	1.0000
20:63275573:GCAGC:G	acceptor_loss	1.0000
20:63275574:CAGCA:C	acceptor_loss	1.0000
20:63275575:A:AG	acceptor_gain	1.0000
20:63275576:G:GA	acceptor_gain	1.0000
20:63275576:GC:G	acceptor_gain	1.0000
20:63275576:GCATC:G	acceptor_gain	1.0000
20:63275641:G:GG	donor_gain	1.0000
20:63276478:A:AG	acceptor_gain	1.0000
20:63276479:G:GG	acceptor_gain	1.0000
20:63276479:GCTTT:G	acceptor_gain	1.0000
20:63276580:G:GT	donor_gain	1.0000
20:63276583:GAT:G	donor_gain	1.0000
20:63276612:G:GT	donor_gain	1.0000
20:63276645:GGA:G	donor_gain	1.0000
20:63276646:GA:G	donor_gain	1.0000
20:63276647:A:G	donor_gain	1.0000
20:63276648:TAAGG:T	donor_loss	1.0000
20:63276649:AAG:A	donor_loss	1.0000
20:63276650:AG:A	donor_loss	1.0000
20:63276651:GG:G	donor_loss	1.0000
20:63276652:G:C	donor_loss	1.0000
20:63277330:G:GG	donor_gain	1.0000
20:63278108:C:A	acceptor_gain	1.0000
20:63278115:A:AG	acceptor_gain	1.0000
20:63278115:A:AT	acceptor_loss	1.0000
20:63278116:G:GA	acceptor_gain	1.0000
20:63278116:GA:G	acceptor_gain	1.0000
20:63278116:GAGT:G	acceptor_gain	1.0000
20:63278116:GAGTC:G	acceptor_gain	1.0000

AlphaMissense

2705 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63276094:T:C	C22R	1.000
20:63276124:T:A	W32R	1.000
20:63276124:T:C	W32R	1.000
20:63276126:G:C	W32C	1.000
20:63276126:G:T	W32C	1.000
20:63276130:A:C	S34R	1.000
20:63276132:T:A	S34R	1.000
20:63276132:T:G	S34R	1.000
20:63276154:T:C	C42R	1.000
20:63276156:C:G	C42W	1.000
20:63276178:C:A	R50S	1.000
20:63276481:T:C	F58L	1.000
20:63276483:T:A	F58L	1.000
20:63276483:T:G	F58L	1.000
20:63276487:C:A	R60S	1.000
20:63276502:G:C	D65H	1.000
20:63276508:T:A	W67R	1.000
20:63276508:T:C	W67R	1.000
20:63281337:C:A	A225D	1.000
20:63276094:T:A	C22S	0.999
20:63276095:G:A	C22Y	0.999
20:63276095:G:C	C22S	0.999
20:63276096:T:G	C22W	0.999
20:63276103:T:A	C25S	0.999
20:63276103:T:C	C25R	0.999
20:63276104:G:C	C25S	0.999
20:63276125:G:C	W32S	0.999
20:63276143:G:A	G38D	0.999
20:63276148:T:A	W40R	0.999
20:63276148:T:C	W40R	0.999

dbSNP variants (sampled 300 via entrez): RS1000559806 (20:63283341 A>G), RS1000620740 (20:63279148 T>A), RS1000624378 (20:63287468 G>A,C), RS1000646106 (20:63290250 A>G), RS1000882496 (20:63279521 C>A,T), RS1000934126 (20:63279757 A>G), RS1001515904 (20:63287288 C>A,T), RS1001643252 (20:63275047 C>T), RS1001644358 (20:63289852 C>A,T), RS1001820016 (20:63286995 G>A,T), RS1001860639 (20:63279801 A>G), RS1001993191 (20:63283639 A>G), RS1001996107 (20:63290279 A>G), RS1002263336 (20:63286207 G>A), RS1002836838 (20:63285347 G>A,C)

Disease associations

OMIM: gene MIM:608377 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): breast ductal adenocarcinoma (MONDO:0005590), developmental and epileptic encephalopathy (MONDO:0100620), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465332 (SINGLE PROTEIN)

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.30	EC50	500	nM	CHEMBL259181

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-2-[[2-(2,3-dihydro-1H-inden-5-yloxy)-9-[(4-phenylphenyl)methyl]purin-6-yl]amino]-3-phenylpropan-1-ol	1973668: Inhibition of ARFGAP1 (unknown origin)	ec50	0.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	3
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Bortezomib	decreases expression	1
Air Pollutants	increases abundance, affects expression	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression, affects cotreatment	1
Fluorouracil	increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Quercetin	decreases phosphorylation	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5326170	Binding	Inhibition of ARFGAP1 (unknown origin)	Ras superfamily GTPase activating proteins in cancer: Potential therapeutic targets? — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT04727970	PHASE1	COMPLETED	Tricaprilin Infantile Spasms Pilot Study
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT03876444	PHASE2/PHASE3	UNKNOWN	Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms
NCT05279118	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Ketogenic Diet vs ACTH for the Treatment of Children With West Syndrome
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT04302116	Not specified	RECRUITING	Vigabatrin With High Dose Prednisolone Combination Therapy vs Vigabatrin Alone for Infantile Spasm
NCT05538936	Not specified	COMPLETED	The Effect of Spa and Massage on Babies on Colic Symptoms
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06266234	Not specified	RECRUITING	Characterization by Automated System on Infantile Spasmes