AGAP1

Summary

AGAP1 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 1, HGNC:16922) is a protein-coding gene on chromosome 2q37.2, encoding Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 (Q9UPQ3). GTPase-activating protein for ARF1 and, to a lesser extent, ARF5.

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.

Source: NCBI Gene 116987 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebral palsy (Moderate, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 433 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001037131

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16922
Approved symbol	AGAP1
Name	ArfGAP with GTPase domain, ankyrin repeat and PH domain 1
Location	2q37.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1099, GGAP1
Ensembl gene	ENSG00000157985
Ensembl biotype	protein_coding
OMIM	608651
Entrez	116987

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000304032, ENST00000336665, ENST00000402604, ENST00000409457, ENST00000409538, ENST00000418654, ENST00000448025, ENST00000453371, ENST00000466575, ENST00000482882, ENST00000635100, ENST00000699337

RefSeq mRNA: 4 — MANE Select: NM_001037131 NM_001037131, NM_001244888, NM_001412122, NM_014914

CCDS: CCDS2514, CCDS33408, CCDS58756

Canonical transcript exons

ENST00000304032 — 18 exons

Exon	Start	End
ENSE00001036351	236036561	236036715
ENSE00001209311	235968462	235968623
ENSE00001290187	235740963	235741048
ENSE00001293217	235799367	235799522
ENSE00001294428	235883345	235883449
ENSE00001298918	235709179	235709237
ENSE00001312059	235744698	235744839
ENSE00001312662	235797759	235797886
ENSE00001313988	235807239	235807331
ENSE00001338196	235930765	235930923
ENSE00001362210	235908738	235908906
ENSE00002508827	235717557	235717644
ENSE00002534885	235750354	235750488
ENSE00003485896	236040751	236040841
ENSE00003678611	236049059	236049281
ENSE00003722172	236120192	236120447
ENSE00003842054	236123919	236131793
ENSE00003848629	235494043	235494849

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6050 / max 607.7213, expressed in 1545 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26188	5.9604	1433
26200	3.7718	621
26187	1.5117	663
26189	0.5611	291
26190	0.3602	151
26198	0.1684	71
26186	0.1060	61
202618	0.0948	29
26199	0.0707	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	98.01	gold quality
cortical plate	UBERON:0005343	97.83	gold quality
paraflocculus	UBERON:0005351	96.44	gold quality
superior vestibular nucleus	UBERON:0007227	95.72	gold quality
sural nerve	UBERON:0015488	95.64	gold quality
inferior vagus X ganglion	UBERON:0005363	95.61	gold quality
corpus callosum	UBERON:0002336	95.48	gold quality
pons	UBERON:0000988	95.47	gold quality
parietal lobe	UBERON:0001872	95.09	gold quality
postcentral gyrus	UBERON:0002581	94.98	gold quality
middle frontal gyrus	UBERON:0002702	94.80	gold quality
ventral tegmental area	UBERON:0002691	94.16	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.00	gold quality
cerebellar vermis	UBERON:0004720	93.98	gold quality
medulla oblongata	UBERON:0001896	93.44	gold quality
subthalamic nucleus	UBERON:0001906	93.42	gold quality
globus pallidus	UBERON:0001875	93.38	gold quality
medial globus pallidus	UBERON:0002477	93.14	gold quality
lateral globus pallidus	UBERON:0002476	92.65	gold quality
superior frontal gyrus	UBERON:0002661	92.31	gold quality
entorhinal cortex	UBERON:0002728	91.99	gold quality
substantia nigra pars compacta	UBERON:0001965	91.87	gold quality
temporal lobe	UBERON:0001871	91.74	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.66	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.63	gold quality
prefrontal cortex	UBERON:0000451	91.58	gold quality
amygdala	UBERON:0001876	91.47	gold quality
corpus epididymis	UBERON:0004359	91.38	gold quality
Ammon’s horn	UBERON:0001954	90.98	gold quality
frontal cortex	UBERON:0001870	90.97	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	78.00
E-HCAD-25	yes	19.35
E-GEOD-137537	yes	16.93
E-ANND-3	yes	5.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

378 targeting AGAP1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 11)

• overexpression inhibited formation of platelet-derived growth factor-induced ruffles and also induced loss of actin stress fibers (PMID:12388557)
• AGAP1 is a novel binding partner of nitric oxide-sensitive guanylyl cyclase (PMID:15381706)
• CENTG2 is an intriguing candidate gene that merits further scrutiny for its role in autism. (PMID:15892143)
• The AGAP1 has been found to associate with the adaptor protein complex AP-3 and regulate the function of AP-3 endosomes. (PMID:16079295)
• AGAP1 is unique among the AZAPs in its specificity for Arf1, and this activity is dependent on its NH(2)-terminal GTPase-like domain. AGAP1 induce reciprocal activation of Arf6. (PMID:18003747)
• GTP-binding protein-like domain of AGAP1 is protein binding site that allosterically regulates ArfGAP protein catalytic activity. (PMID:22453919)
• The effect of AGAP1 Knockdown could be rescued by FLAG-AGAP1, but not by an AGAP1 mutant that did not bind Kif2A efficiently, ArfGAP1-HA or Kif2A-GFP. The results support the hypothesis that the Kif2A.AGAP1 complex contributes to control of cytoskeleton remodeling involved in cell movement. (PMID:27531749)
• 2 Arf GAPs, ASAP1 and AGAP1, have been found to bind directly to and influence the activity of myosins and kinesins, motor proteins associated with filamentous actin and microtubules, respectively. (PMID:28430047)
• AGAP1 regulates subcellular localization of FilGAP and control cancer cell invasion. (PMID:31785816)
• CircAGAP1 promotes tumor progression by sponging miR-15-5p in clear cell renal cell carcinoma. (PMID:33618745)
• Crystal structure of the GTP-binding protein-like domain of AGAP1. (PMID:33830075)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	agap1	ENSDARG00000062123
mus_musculus	Agap1	ENSMUSG00000055013
rattus_norvegicus	Agap1	ENSRNOG00000019476

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), 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), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 — Q9UPQ3 (reviewed: Q9UPQ3)

Alternative names: Centaurin-gamma-2, GTP-binding and GTPase-activating protein 1

All UniProt accessions (7): Q9UPQ3, A0A0U1RRF1, C9J8Z2, E7EUN2, H7C0A7, H7C211, X5D293

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer. Interacts with several subunits of the AP-3 protein complex: AP3M1, AP3S1 and AP3S2. Interacts with GUCY1A3 and GUCY1B3.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated on tyrosines.

Activity regulation. GAP activity stimulated by phosphatidylinositol 3,4,5-trisphosphate (PIP3) and, to a lesser extent, by phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphatidic acid potentiates PIP2 stimulation.

Domain organisation. The PH domain mediates AP-3 binding.

Similarity. Belongs to the centaurin gamma-like family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UPQ3-1	1	yes
Q9UPQ3-2	2
Q9UPQ3-3	3

RefSeq proteins (5): NP_001032208, NP_001231817, NP_001399051, NP_001423055, NP_055729 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR001806	Small_GTPase	Family
IPR001849	PH_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR051282	Arf-GAP_GTPase_ANK_PH	Family

Pfam: PF00071, PF01412, PF12796

UniProt features (48 total): strand 7, sequence variant 6, compositionally biased region 5, modified residue 5, helix 5, region of interest 4, domain 3, binding site 3, splice variant 3, mutagenesis site 2, repeat 2, chain 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9UVL	X-RAY DIFFRACTION	2.49
7EB6	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UPQ3-F1	72.01	0.42

Functional residue map

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

Ligand- & substrate-binding residues (3): 78–85; 122–126; 178–181

Post-translational modifications (5): 1, 521, 605, 663, 836

Mutagenesis-validated functional residues (2):

Position	Phenotype
647	loss of gap activity.
652	loss of gap activity. no effect on ap-3-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 248 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, RNGTGGGC_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, PATIL_LIVER_CANCER, TCF4_Q5, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOBP_CELL_JUNCTION_ORGANIZATION, ONKEN_UVEAL_MELANOMA_UP, THEODOROU_MAMMARY_TUMORIGENESIS, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, HIF1_Q3, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, LIU_CMYB_TARGETS_UP

GO Biological Process (2): protein transport (GO:0015031), regulation of modification of postsynaptic structure (GO:0099159)

GO Molecular Function (8): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), GTP binding (GO:0005525), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), nucleotide binding (GO:0000166), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): postsynaptic endosome (GO:0098845), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
intracellular protein localization	1
establishment of protein localization	1
modification of postsynaptic structure	1
regulation of modification of synaptic structure	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
lipid binding	1
transition metal ion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
cation binding	1
endosome	1
postsynapse	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGAP1	ARF1	P10947	809
AGAP1	ARF5	P26437	702
AGAP1	AP1S1	P61966	667
AGAP1	GBX2	P52951	617
AGAP1	GOLPH3	Q9H4A6	611
AGAP1	ARF6	P26438	597
AGAP1	ANK1	P16157	570
AGAP1	ANK3	Q12955	570
AGAP1	LAMP1	P11279	538
AGAP1	PLEK2	Q9NYT0	507
AGAP1	KIF2A	O00139	488
AGAP1	PLEK	P08567	485
AGAP1	RASA1	P20936	478
AGAP1	HSPA1L	P34931	424
AGAP1	ZCCHC14	Q8WYQ9	422

IntAct

109 interactions, top by confidence:

A	B	Type	Score
TANC2	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
ZNF534	AGAP1	psi-mi:“MI:0915”(physical association)	0.560
RSPH14	AGAP1	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
FLCN	ZNF609	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
GRB7	AGAP1	psi-mi:“MI:0915”(physical association)	0.370
SMN1	AGAP1	psi-mi:“MI:0915”(physical association)	0.370
TK1	AGAP1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
MED13L	IGKV1-8	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
AGAP1	AGAP3	psi-mi:“MI:0914”(association)	0.350
AGAP3	AHCYL1	psi-mi:“MI:0914”(association)	0.350
CLNS1A	EPB41	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): SQSTM1 (Affinity Capture-Western), AGAP1 (Affinity Capture-MS), AGAP1 (Affinity Capture-MS), AGAP1 (Affinity Capture-MS), AGAP1 (Affinity Capture-MS), RHOA (Affinity Capture-Western), AGAP1 (Affinity Capture-Western), AGAP1 (Reconstituted Complex), ARF1 (Biochemical Activity), ARF6 (Biochemical Activity), RAC1 (Reconstituted Complex), CDC42 (Reconstituted Complex), RHOA (Reconstituted Complex), AGAP1 (Affinity Capture-MS), AGAP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IVA4, A1Z7A6, A4D256, A6N3Q4, A8XQD5, B3M301, B3P8A3, B4G437, B4HGG6, B4JII0, B4K799, B4M0H8, B4NBP4, B4PL32, B4QSF0, B7WN72, G5EFD2, O02626, O43078, O43166, O60729, P24583, P34400, P34680, P43125, P50527, P81299, Q00684, Q07292, Q19469, Q19857, Q298L4, Q59NH8, Q5B323, Q61UC4, Q6GQT0, Q6NRL1, Q6PFY9, Q8BXK8, Q8I0P1

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	56.0×	3e-09
Activation of BAD and translocation to mitochondria	6	54.4×	8e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	48.0×	2e-07
Activation of BH3-only proteins	6	35.5×	8e-07
RHO GTPases activate PKNs	7	26.4×	5e-07
Intrinsic Pathway for Apoptosis	6	20.9×	1e-05
Apoptosis	7	14.0×	2e-05
RHOQ GTPase cycle	6	12.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	18.8×	6e-04
intracellular protein localization	8	7.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	236
Likely benign	133
Benign	34

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545276	NC_000002.12:g.(?235927172)(236034017_?)del	Likely pathogenic

SpliceAI

7076 predictions. Top by Δscore:

Variant	Effect	Δscore
2:235494850:G:GA	donor_loss	1.0000
2:235494851:T:A	donor_loss	1.0000
2:235566582:GTGCT:G	donor_gain	1.0000
2:235709174:TTCA:T	acceptor_loss	1.0000
2:235709177:A:AG	acceptor_gain	1.0000
2:235709178:G:GA	acceptor_gain	1.0000
2:235709178:GAT:G	acceptor_gain	1.0000
2:235709233:AAGTG:A	donor_gain	1.0000
2:235709235:GTG:G	donor_gain	1.0000
2:235709237:GGT:G	donor_loss	1.0000
2:235709238:G:T	donor_loss	1.0000
2:235709239:T:A	donor_loss	1.0000
2:235717551:TTTCA:T	acceptor_loss	1.0000
2:235717552:TTCAG:T	acceptor_loss	1.0000
2:235717553:TCAG:T	acceptor_loss	1.0000
2:235717554:CAGG:C	acceptor_loss	1.0000
2:235717555:A:AG	acceptor_gain	1.0000
2:235717555:A:AT	acceptor_loss	1.0000
2:235717555:AG:A	acceptor_gain	1.0000
2:235717555:AGG:A	acceptor_gain	1.0000
2:235717556:G:GA	acceptor_gain	1.0000
2:235717556:GG:G	acceptor_gain	1.0000
2:235717556:GGG:G	acceptor_gain	1.0000
2:235717556:GGGA:G	acceptor_gain	1.0000
2:235717556:GGGAA:G	acceptor_gain	1.0000
2:235717642:A:T	donor_gain	1.0000
2:235717644:GGTAT:G	donor_loss	1.0000
2:235717645:GT:G	donor_loss	1.0000
2:235717646:T:A	donor_loss	1.0000
2:235741045:GCAG:G	donor_gain	1.0000

AlphaMissense

5615 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:235709202:T:A	W63R	1.000
2:235709202:T:C	W63R	1.000
2:235709204:G:C	W63C	1.000
2:235709204:G:T	W63C	1.000
2:235709230:T:C	L72P	1.000
2:235717557:G:A	G75R	1.000
2:235717557:G:C	G75R	1.000
2:235717558:G:A	G75E	1.000
2:235717566:G:C	G78R	1.000
2:235717566:G:T	G78C	1.000
2:235717567:G:A	G78D	1.000
2:235717567:G:T	G78V	1.000
2:235717578:A:C	S82R	1.000
2:235717580:C:A	S82R	1.000
2:235717580:C:G	S82R	1.000
2:235717582:G:A	G83D	1.000
2:235717585:A:T	K84M	1.000
2:235717586:G:C	K84N	1.000
2:235717586:G:T	K84N	1.000
2:235717588:C:T	S85F	1.000
2:235717594:T:A	L87Q	1.000
2:235717594:T:C	L87P	1.000
2:235717603:G:C	R90P	1.000
2:235717605:T:G	Y91D	1.000
2:235717609:T:C	L92P	1.000
2:235717644:G:C	G104R	1.000
2:235740971:T:C	F107L	1.000
2:235740972:T:C	F107S	1.000
2:235740973:C:A	F107L	1.000
2:235740973:C:G	F107L	1.000

dbSNP variants (sampled 300 via entrez): RS1000004104 (2:235534446 A>G), RS1000016582 (2:235824191 T>C), RS1000018030 (2:235931595 G>A), RS1000021552 (2:235991525 C>T), RS1000021746 (2:236035455 T>C), RS1000022082 (2:235964381 A>G), RS1000023579 (2:235629091 T>A), RS1000024423 (2:236039791 G>A,T), RS1000024644 (2:236068081 G>A), RS1000041890 (2:235791121 A>G), RS1000063741 (2:236000951 A>C,T), RS1000065574 (2:235593015 T>G), RS1000066102 (2:235504723 A>C,G), RS1000068505 (2:235594714 G>C), RS1000079506 (2:235513934 T>C)

Disease associations

OMIM: gene MIM:608651 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebral palsy	Moderate	Autosomal dominant

Mondo (2): autism (MONDO:0005260), cerebral palsy (MONDO:0006497)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001565_1	Schizophrenia	8.000000e-08
GCST002013_3	Menarche (age at onset)	4.000000e-06
GCST003205_1	Cardiovascular disease in hypertension (calcium channel blocker interaction)	9.000000e-07
GCST004275_4	Venlafaxine response in generalised anxiety disorder (responders vs non-responders after 24 weeks)	4.000000e-06
GCST004412_3	Craniofacial microsomia	5.000000e-13
GCST005173_72	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	2.000000e-06
GCST005993_2	Mean corpuscular hemoglobin	3.000000e-08
GCST006011_23	Mean corpuscular volume	5.000000e-09
GCST008467_4	Aspartate aminotransferase levels in non-alcoholic fatty liver disease	5.000000e-06
GCST010988_130	Adult body size	1.000000e-08
GCST012005_2	Anterior thalamic nuclei volume	3.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0007767	response to calcium channel blocker
EFO:0004723	coronary artery calcification
EFO:0004527	mean corpuscular hemoglobin
EFO:0004736	aspartate aminotransferase measurement
EFO:0006935	thalamus volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002547	Cerebral Palsy	C10.228.140.140.254

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1869295	AGAP1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	5
methylmercuric chloride	increases expression, affects cotreatment	3
Valproic Acid	affects expression, increases expression, increases methylation	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation, affects cotreatment	1
terbufos	decreases methylation	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression, increases abundance, affects cotreatment	1
perfluorooctanoic acid	affects methylation	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	affects methylation	1
maleic acid	increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation, affects cotreatment	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, affects methylation, increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1PM	HAP1 AGAP1 (-) 1	Cancer cell line	Male
CVCL_E1PN	HAP1 AGAP1 (-) 2	Cancer cell line	Male
CVCL_E1PP	HAP1 AGAP1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder