ASAP1

Summary

ASAP1 (ArfGAP with SH3 domain, ankyrin repeat and PH domain 1, HGNC:2720) is a protein-coding gene on chromosome 8q24.21-q24.22, encoding Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 (Q9ULH1). Possesses phosphatidylinositol 4,5-bisphosphate-dependent GTPase-activating protein activity for ARF1 (ADP ribosylation factor 1) and ARF5 and a lesser activity towards ARF6.

This gene encodes an ADP-ribosylation factor (ARF) GTPase-activating protein. The GTPase-activating activity is stimulated by phosphatidylinositol 4,5-biphosphate (PIP2), and is greater towards ARF1 and ARF5, and lesser for ARF6. This gene maybe involved in regulation of membrane trafficking and cytoskeleton remodeling. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 50807 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 132 total
• Druggable target: yes
• MANE Select transcript: NM_018482

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2720
Approved symbol	ASAP1
Name	ArfGAP with SH3 domain, ankyrin repeat and PH domain 1
Location	8q24.21-q24.22
Locus type	gene with protein product
Status	Approved
Aliases	PAP, KIAA1249, ZG14P, CENTB4
Ensembl gene	ENSG00000153317
Ensembl biotype	protein_coding
OMIM	605953
Entrez	50807

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000357668, ENST00000518721, ENST00000518957, ENST00000519169, ENST00000519483, ENST00000520189, ENST00000520342, ENST00000520625, ENST00000520927, ENST00000521057, ENST00000521075, ENST00000521426, ENST00000524018, ENST00000524124, ENST00000524299, ENST00000524367, ENST00000871692, ENST00000871693, ENST00000913391, ENST00000962395

RefSeq mRNA: 5 — MANE Select: NM_018482 NM_001247996, NM_001362924, NM_001362925, NM_001362926, NM_018482

CCDS: CCDS6362, CCDS75788

Canonical transcript exons

ENST00000518721 — 30 exons

Exon	Start	End
ENSE00002103811	130401885	130401970
ENSE00003458605	130115628	130115735
ENSE00003459901	130187236	130187285
ENSE00003482469	130124013	130124104
ENSE00003483953	130159864	130159964
ENSE00003484563	130167536	130167622
ENSE00003488689	130134296	130134344
ENSE00003490973	130060579	130061069
ENSE00003501281	130358017	130358143
ENSE00003502024	130152736	130152805
ENSE00003516039	130079902	130079971
ENSE00003519417	130179264	130179349
ENSE00003519929	130118161	130118246
ENSE00003521045	130188109	130188183
ENSE00003525707	130214556	130214701
ENSE00003537164	130168992	130169067
ENSE00003540393	130236922	130236994
ENSE00003554432	130136951	130137038
ENSE00003564408	130116880	130116995
ENSE00003579561	130116678	130116745
ENSE00003590378	130125956	130126089
ENSE00003594579	130180751	130180880
ENSE00003608850	130076348	130076406
ENSE00003611944	130091973	130092143
ENSE00003626273	130112094	130112322
ENSE00003634422	130057954	130058076
ENSE00003648166	130118489	130118675
ENSE00003680153	130127927	130128090
ENSE00003744040	130052104	130054805
ENSE00003843520	130443460	130443674

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5912 / max 175.9857, expressed in 1634 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95028	13.5303	1593
95029	2.6827	1217
95030	0.7242	466
95006	0.4423	226
95031	0.3243	170
95032	0.2721	124
95033	0.2522	112
95027	0.1888	54
95000	0.1090	22
95004	0.0252	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.20	gold quality
sural nerve	UBERON:0015488	98.02	gold quality
trabecular bone tissue	UBERON:0002483	96.71	gold quality
sperm	CL:0000019	96.26	gold quality
calcaneal tendon	UBERON:0003701	96.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.13	gold quality
oocyte	CL:0000023	96.11	gold quality
secondary oocyte	CL:0000655	96.03	gold quality
visceral pleura	UBERON:0002401	95.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.56	gold quality
lower lobe of lung	UBERON:0008949	95.13	gold quality
colonic epithelium	UBERON:0000397	94.75	gold quality
bone marrow	UBERON:0002371	94.71	gold quality
blood	UBERON:0000178	94.70	gold quality
stromal cell of endometrium	CL:0002255	94.57	gold quality
parietal pleura	UBERON:0002400	94.54	gold quality
amniotic fluid	UBERON:0000173	94.32	gold quality
skin of hip	UBERON:0001554	94.17	gold quality
ventricular zone	UBERON:0003053	94.05	gold quality
adrenal tissue	UBERON:0018303	94.01	gold quality
parietal lobe	UBERON:0001872	93.97	gold quality
tibia	UBERON:0000979	93.91	gold quality
bone marrow cell	CL:0002092	93.83	gold quality
postcentral gyrus	UBERON:0002581	93.83	gold quality
entorhinal cortex	UBERON:0002728	93.75	gold quality
dorsal root ganglion	UBERON:0000044	93.74	gold quality
pleura	UBERON:0000977	93.59	gold quality
placenta	UBERON:0001987	93.53	gold quality
superior frontal gyrus	UBERON:0002661	93.43	gold quality
middle temporal gyrus	UBERON:0002771	93.37	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	2209.09
E-CURD-119	yes	1934.77
E-MTAB-6678	yes	8.76
E-HCAD-13	yes	8.22
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1

miRNA regulators (miRDB)

128 targeting ASAP1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872

Literature-anchored findings (GeneRIF, showing 40)

• DEF-1 alters cell motility through the deactivation of ARF1. In contrast, the inhibition of cell spreading by DEF-1 was not dependent on GAP activity, indicating that spreading and motility are altered by DEF-1 through different pathways. (PMID:11773070)
• These results suggest that POB1 interacts with PAG2 through its proline-rich motif, thereby regulating cell migration (PAG2). (PMID:12149250)
• involved in peripheral focal adhesions, directed by CRKL protein (PMID:12522101)
• DDEF1 overexpression may be a pathogenetically relevant consequence of chromosome 8q amplification, which commonly occurs in high-grade uveal melanomas (PMID:15897555)
• Results support a model that regulation of GAP (GTPase-activating protein) activity of ASAP1 involves conformational changes, coincident with recruitment to a membrane surface and following the specific binding of phosphatidylinositol 4,5-bisphosphate. (PMID:16038802)
• Results suggest that the AMAP1/cortactin complex, which is not detected in normal mammary epithelial cells, is an excellent drug target for cancer therapeutics. (PMID:16636290)
• ASAP3 functions nonredundantly with ASAP1 to control cell movement and may have a role in cancer cell invasion. (PMID:18400762)
• study suggests that the ASAP1 gene plays a role in prostate cancer metastasis and may represent a therapeutic target and/or biomarker for metastatic disease (PMID:18519696)
• ASAP1, like FIP3, functions as a component of the endocytic recycling compartment (PMID:18685082)
• Results indicate that monocyte differentiation involves enhancement of IRES activity, by which protein levels of AMAP1 are primarily upregulated. (PMID:18843202)
• Autoinhibition of Arf GTPase-activating protein activity by the BAR domain in ASAP1 (PMID:19017632)
• ASAP1 can contribute to the dissemination of a variety of tumor types and represent a potential target for cancer therapy. (PMID:20154719)
• GEFH1 was identified as binding partner for the BAR domain of ASAP1.GEFH1 is a negative regulator of podosomes. (PMID:21352810)
• Data suggest that GEP100-Arf6-AMAP1-cortactin pathway, activated by VEGFR2, appears to be common in angiogenesis and cancer invasion and metastasis, and provides their new therapeutic targets. (PMID:21858086)
• found that AMAP1 had the ability to bind directly to PRKD2 and hence to make a complex with the cytoplasmic tail of the beta1 subunit (PMID:22734003)
• Data show that co-overexpression of GEP100 and AMAP1 (ASAP1) correlates with rapidity of the local recurrence. (PMID:24116160)
• results indicated that elevated expression of ASAP1 plays an important role in the progression and metastasis of ovarian cancer (PMID:24427349)
• ASAP1 appears to contribute to the malignant mechanism of LSCC and may represent a significant prognostic marker for laryngeal squamous cell carcinoma patients. (PMID:24788532)
• The activation of NF-kappaB induced translocation of AMAP1 to cytoplasm from cell membrane and nucleus, which resulted in augmented interaction of AMAP1 and IKKbeta (PMID:24865276)
• Rab11-FIP3 coordinates the interactions of ASAP1 and Rab11a with Rabin8. (PMID:25673879)
• High ASAP1 expression, that was reduced after Mycobacterium tuberculosis infection, and rs10956514, are associated with the level of reduction of ASAP1 expression. (PMID:25774636)
• results support the hypothesis that ASAP1 is a positive regulator of NM2A. (PMID:26893376)
• results, specifically, the absence of associations of polymorphisms of ASAP1 with tuberculosis (TB) risk, suggest that ASAP1 may not be a susceptibility gene for TB in Western Chinese Han and Tibetan population (PMID:27227929)
• eIF5B promoted hepatocellular carcinoma cell proliferation and migration in vitro and in vivo partly through increasing ASAP1 expression. (PMID:27694689)
• Less differentiated embryonal and undifferentiated small hepatoblastoma cells progressively lose EGFR and ASAP1 expression. This trend is exaggerated in unresectable, locally invasive or metastatic tumors. (PMID:27910913)
• 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)
• AMAP1 mediated CCL18-induce activation of NF-kappaB and promoted breast cancer metastasis. (PMID:28834540)
• Histone modifications of certain miRNA loci, such as the miR-183-96-182 cistron, are different between epithelial cells and non-epithelial cells (PMID:30509302)
• rs4733781 A allele of ASAP1 is associated with a decreased risk of tuberculosis in Han Chinese. (PMID:31089398)
• Mutations in the ARF N terminus that reduced binding also reduced GAP activity. We conclude that PIP2 regulates binding of ASAP1’s PH domain to the ARF1 N terminus, which may partially regulate GAP activity. (PMID:31591270)
• Circular RNA Sequencing Identifies CircASAP1 as a Key Regulator in Hepatocellular Carcinoma Metastasis. (PMID:31838741)
• Integrative analysis of genomic amplification-dependent expression and loss-of-function screen identifies ASAP1 as a driver gene in triple-negative breast cancer progression. (PMID:32235890)
• Knockout of ASAP1 induces autophagy in papillary thyroid carcinoma by inhibiting the mTOR signaling pathway. (PMID:32307199)
• The BAR domain of the Arf GTPase-activating protein ASAP1 directly binds actin filaments. (PMID:32444496)
• High expression of AMAP1, an ARF6 effector, is associated with elevated levels of PD-L1 and fibrosis of pancreatic cancer. (PMID:32580737)
• ADP ribosylation factor guanylate kinase 1 promotes the malignant phenotype of gastric cancer by regulating focal adhesion kinase activation. (PMID:33639150)
• ASAP1 regulates the uptake of Mycobacterium tuberculosis H37Ra in THP1-derived macrophages by remodeling actin cytoskeleton. (PMID:34058694)
• Loss of ASAP1 in the MMTV-PyMT model of luminal breast cancer activates AKT, accelerates tumorigenesis, and promotes metastasis. (PMID:35181478)
• Clinicopathological Implications of ASAP1 Expression in Hepatocellular Carcinoma. (PMID:36110251)
• Polymorphisms in the ASAP1 and SP110 Genes and Its Association with the Susceptibility to Pulmonary Tuberculosis in a Mongolian Population. (PMID:36249417)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asap1a	ENSDARG00000029463
danio_rerio	asap1b	ENSDARG00000039729
mus_musculus	Asap1	ENSMUSG00000022377
rattus_norvegicus	Asap1	ENSRNOG00000058733

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), 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 with SH3 domain, ANK repeat and PH domain-containing protein 1 — Q9ULH1 (reviewed: Q9ULH1)

Alternative names: 130 kDa phosphatidylinositol 4,5-bisphosphate-dependent ARF1 GTPase-activating protein, ADP-ribosylation factor-directed GTPase-activating protein 1, Development and differentiation-enhancing factor 1, PIP2-dependent ARF1 GAP

All UniProt accessions (7): Q9ULH1, A0A0A0MRE5, E5RFD9, E5RHA9, E5RHD7, H0YBF7, H0YBM4

UniProt curated annotations — full annotation on UniProt →

Function. Possesses phosphatidylinositol 4,5-bisphosphate-dependent GTPase-activating protein activity for ARF1 (ADP ribosylation factor 1) and ARF5 and a lesser activity towards ARF6. May coordinate membrane trafficking with cell growth or actin cytoskeleton remodeling by binding to both SRC and PIP2. May function as a signal transduction protein involved in the differentiation of fibroblasts into adipocytes and possibly other cell types. Part of the ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which direct preciliary vesicle trafficking to mother centriole and ciliogenesis initiation.

Subunit / interactions. Homodimer. Interacts with SRC and CRK. Interacts with RAB11FIP3. Interacts with PTK2B/PYK2. Interacts with CTTN. Interacts (via SH3 domain) with APC. Interacts with REPS2; the interaction is direct. Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport.

Subcellular location. Cytoplasm. Membrane. Golgi apparatus. trans-Golgi network.

Post-translational modifications. Phosphorylated on tyrosine residues by SRC.

Activity regulation. Activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2).

Domain organisation. The PH domain most probably contributes to the phosphoinositide-dependent regulation of ADP ribosylation factors.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULH1-1	2	yes
Q9ULH1-2	1

RefSeq proteins (5): NP_001234925, NP_001349853, NP_001349854, NP_001349855, NP_060952* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR004148	BAR_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR037844	PH_ASAP	Domain
IPR037928	ASAP1_BAR	Domain
IPR038016	ASAP1_SH3	Domain
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR043593	ASAP	Family

Pfam: PF00169, PF01412, PF12796, PF14604, PF16746

UniProt features (48 total): strand 15, compositionally biased region 10, modified residue 9, domain 3, repeat 2, helix 2, region of interest 2, chain 1, splice variant 1, sequence variant 1, turn 1, zinc finger region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2D1X	X-RAY DIFFRACTION	1.9
2DA0	SOLUTION NMR
2ED1	SOLUTION NMR
2RQT	SOLUTION NMR
2RQU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULH1-F1	72.05	0.48

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 (9): 717, 726, 839, 843, 1008, 1027, 1041, 1048, 1128

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5620916	VxPx cargo-targeting to cilium
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly
R-HSA-5620920	Cargo trafficking to the periciliary membrane

MSigDB gene sets: 301 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, GOCC_TRANS_GOLGI_NETWORK, ONKEN_UVEAL_MELANOMA_UP, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_LOBULAR_NORMAL_DN

GO Biological Process (5): cilium assembly (GO:0060271), protein localization to cilium (GO:0061512), positive regulation of membrane tubulation (GO:1903527), cell projection organization (GO:0030030), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (5): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), cadherin binding (GO:0045296), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): Golgi membrane (GO:0000139), podosome (GO:0002102), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), trans-Golgi network membrane (GO:0032588), centriolar satellite (GO:0034451), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1
Organelle biogenesis and maintenance	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
GTPase activity	2
cytoplasm	2
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
protein localization to organelle	1
positive regulation of cellular component organization	1
plasma membrane tubulation	1
regulation of membrane tubulation	1
cellular component organization	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
cell adhesion molecule binding	1
binding	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
actin-based cell projection	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
trans-Golgi network	1
organelle membrane	1
centrosome	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASAP1	IKBKG	Q9Y6K9	970
ASAP1	ARF4	P18085	948
ASAP1	SRC	P12931	947
ASAP1	ARF1	P10947	941
ASAP1	ARF5	P26437	886
ASAP1	RAB11A	P24410	881
ASAP1	RAB11FIP3	O75154	869
ASAP1	ARF6	P26438	827
ASAP1	CTTN	Q14247	797
ASAP1	PXN	P49023	773
ASAP1	ANK2	Q01484	769
ASAP1	ANK1	P16157	759
ASAP1	ANK3	Q12955	743
ASAP1	PTK2B	Q14289	739
ASAP1	PLEK2	Q9NYT0	730

IntAct

107 interactions, top by confidence:

A	B	Type	Score
GRB2	ASAP1	psi-mi:“MI:0915”(physical association)	0.920
ASAP1	SH3KBP1	psi-mi:“MI:0915”(physical association)	0.880
SH3KBP1	ASAP1	psi-mi:“MI:0915”(physical association)	0.880
ASAP1	SH3KBP1	psi-mi:“MI:0403”(colocalization)	0.880
ASAP1	CTTN	psi-mi:“MI:0915”(physical association)	0.770
CTTN	ASAP1	psi-mi:“MI:0407”(direct interaction)	0.770
ASAP1	CTTN	psi-mi:“MI:0407”(direct interaction)	0.770
CTTN	ASAP1	psi-mi:“MI:0915”(physical association)	0.770
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
FYN	ASAP1	psi-mi:“MI:0915”(physical association)	0.700
FYN	ASAP1	psi-mi:“MI:0407”(direct interaction)	0.700
CRK	ASAP1	psi-mi:“MI:0915”(physical association)	0.670
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640

BioGRID (117): ASAP1 (Affinity Capture-MS), ASAP1 (Affinity Capture-MS), RAB11FIP3 (Affinity Capture-Western), ASAP1 (Affinity Capture-Western), ASAP1 (Affinity Capture-Western), ASAP1 (Affinity Capture-Western), ASAP1 (Reconstituted Complex), ASAP1 (Proximity Label-MS), ASAP1 (Proximity Label-MS), ASAP1 (Affinity Capture-MS), ASAP1 (Affinity Capture-MS), ASAP1 (Affinity Capture-MS), ASAP1 (Affinity Capture-MS), ASAP1 (Affinity Capture-RNA), ASAP1 (Reconstituted Complex)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z7A6, D3ZHV2, E9Q557, F1LMV6, F1M0Z1, G3V7L1, O43150, O60229, O60437, O75962, O97592, O97902, P0CE94, P0CE95, P10911, P11530, P11531, P11532, P11533, P15924, P30427, P33175, P46939, Q03001, Q0KL02, Q15149, Q1AAU6, Q1LUA6, Q5GN48, Q6ZWR6, Q7SIG6, Q8CIS0, Q8NF91, Q8WXH0, Q91ZU6, Q92817, Q95RG8, Q9BXL7

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

2 interactions.

A	Effect	B	Mechanism
PTK2B	“down-regulates activity”	ASAP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
InlB-mediated entry of Listeria monocytogenes into host cell	6	81.6×	5e-09
Regulation of signaling by CBL	8	70.9×	6e-11
Negative regulation of MET activity	6	55.6×	5e-08
Downstream signal transduction	8	54.4×	4e-10
Nephrin family interactions	6	51.0×	9e-08
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	51.0×	2e-06
Signaling by CSF1 (M-CSF) in myeloid cells	8	49.4×	6e-10
EGFR downregulation	7	43.3×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
Fc-gamma receptor signaling pathway involved in phagocytosis	5	58.5×	3e-06
peptidyl-tyrosine phosphorylation	6	42.1×	2e-06
positive regulation of actin filament polymerization	7	38.5×	2e-07
ephrin receptor signaling pathway	6	34.4×	3e-06
negative regulation of T cell receptor signaling pathway	5	30.5×	5e-05
cellular response to transforming growth factor beta stimulus	5	23.0×	2e-04
epidermal growth factor receptor signaling pathway	5	20.6×	2e-04
T cell receptor signaling pathway	7	17.7×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

6804 predictions. Top by Δscore:

Variant	Effect	Δscore
8:130054801:CCAAT:C	acceptor_gain	1.0000
8:130054802:CAAT:C	acceptor_gain	1.0000
8:130054802:CAATC:C	acceptor_gain	1.0000
8:130054803:AATC:A	acceptor_loss	1.0000
8:130054804:AT:A	acceptor_gain	1.0000
8:130054804:ATCT:A	acceptor_loss	1.0000
8:130054805:TCTG:T	acceptor_loss	1.0000
8:130054806:C:CA	acceptor_loss	1.0000
8:130054806:C:CC	acceptor_gain	1.0000
8:130054807:T:A	acceptor_loss	1.0000
8:130057948:ACGT:A	donor_loss	1.0000
8:130057950:GTA:G	donor_loss	1.0000
8:130057952:A:AC	donor_gain	1.0000
8:130057952:AC:A	donor_gain	1.0000
8:130057952:ACCC:A	donor_loss	1.0000
8:130057953:C:CA	donor_loss	1.0000
8:130057953:C:CC	donor_gain	1.0000
8:130057953:CC:C	donor_gain	1.0000
8:130057953:CCCA:C	donor_gain	1.0000
8:130057957:CCA:C	donor_gain	1.0000
8:130058073:TCCC:T	acceptor_gain	1.0000
8:130058074:CCC:C	acceptor_gain	1.0000
8:130058074:CCCCT:C	acceptor_gain	1.0000
8:130058075:CC:C	acceptor_gain	1.0000
8:130058075:CCC:C	acceptor_gain	1.0000
8:130058076:CC:C	acceptor_gain	1.0000
8:130058076:CCTTA:C	acceptor_loss	1.0000
8:130058077:C:CC	acceptor_gain	1.0000
8:130058077:C:T	acceptor_gain	1.0000
8:130058078:T:C	acceptor_gain	1.0000

AlphaMissense

7381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:130054750:A:T	V1124D	1.000
8:130054752:A:C	F1123L	1.000
8:130054752:A:T	F1123L	1.000
8:130054754:A:G	F1123L	1.000
8:130054765:A:G	F1119S	1.000
8:130054772:C:A	G1117W	1.000
8:130054772:C:G	G1117R	1.000
8:130054772:C:T	G1117R	1.000
8:130054801:C:T	G1107D	1.000
8:130054802:C:G	G1107R	1.000
8:130057959:A:G	W1104R	1.000
8:130057959:A:T	W1104R	1.000
8:130057982:A:T	V1096D	1.000
8:130058006:A:G	F1088S	1.000
8:130058012:A:G	L1086P	1.000
8:130058012:A:T	L1086H	1.000
8:130058035:G:C	C1078W	1.000
8:130058037:A:G	C1078R	1.000
8:130092037:T:A	R836S	1.000
8:130092037:T:G	R836S	1.000
8:130115681:A:G	W707R	1.000
8:130115681:A:T	W707R	1.000
8:130118645:C:A	K546N	1.000
8:130118645:C:G	K546N	1.000
8:130125960:A:G	L504P	1.000
8:130126025:C:A	R482S	1.000
8:130126025:C:G	R482S	1.000
8:130126026:C:A	R482M	1.000
8:130126026:C:G	R482T	1.000
8:130126030:G:C	H481D	1.000

dbSNP variants (sampled 300 via entrez): RS1000019130 (8:130131395 C>A,G), RS1000026628 (8:130072305 G>A), RS1000036292 (8:130274453 T>C), RS1000046456 (8:130440325 G>A), RS1000056608 (8:130177980 T>A), RS1000065819 (8:130421223 T>C,G), RS1000067209 (8:130218858 T>C), RS1000076676 (8:130371197 A>G), RS1000077303 (8:130421653 A>C,T), RS1000083451 (8:130212861 G>A,C), RS1000094682 (8:130243919 A>G), RS1000098451 (8:130232342 A>G,T), RS1000101093 (8:130433399 T>C), RS1000107648 (8:130144007 G>A,C), RS1000107838 (8:130271989 A>C)

Disease associations

OMIM: gene MIM:605953 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000425_8	Multiple sclerosis	2.000000e-06
GCST002810_1	Tuberculosis	4.000000e-12
GCST002810_2	Tuberculosis	3.000000e-11
GCST002875_86	Diisocyanate-induced asthma	1.000000e-06
GCST003263_73	Post bronchodilator FEV1 in COPD	4.000000e-06
GCST004599_66	Mean platelet volume	2.000000e-23
GCST004603_77	Platelet count	3.000000e-10
GCST006418_12	Progressive supranuclear palsy	5.000000e-07
GCST006418_3	Progressive supranuclear palsy	5.000000e-07
GCST008161_120	Waist circumference adjusted for body mass index	9.000000e-06
GCST010002_312	Refractive error	3.000000e-09
GCST010303_50	Nevus count or cutaneous melanoma	3.000000e-10
GCST011743_59	HDL cholesterol levels in HIV infection	8.000000e-06
GCST012038_4	Sleep duration (> 10 hours)	5.000000e-08
GCST90000025_380	Appendicular lean mass	6.000000e-13
GCST90002392_521	Mean corpuscular volume	3.000000e-18
GCST90002395_16	Mean platelet volume	9.000000e-71
GCST90002401_470	Platelet distribution width	8.000000e-10

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0004314	forced expiratory volume
EFO:0004309	platelet count
EFO:0007789	BMI-adjusted waist circumference
EFO:0004632	nevus count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146311 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

6 measured of 7 human assays (10 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
N-(3-chloro-4-methylphenyl)-3-nitro-4-(2-oxolanylmethylamino)benzamide	IC50	5200 nM
cid_2136917	IC50	7440 nM
MLS000587937	IC50	10900 nM
SMR000185905	IC50	12700 nM
N-{[1-(2,4-dichlorobenzyl)-1H-indol-3-yl]methylene}-4H-1,2,4-triazol-4-amine	IC50	12900 nM
2-[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-oxo-1-pyridazinyl]-N-[4-(1-tetrazolyl)phenyl]acetamide	IC50	38500 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Doxorubicin	decreases expression	2
Nickel	increases expression	2
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
aflatoxin B2	decreases methylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2114901	Functional	PubChem BioAssay. Fluorescence polarization-based biochemical high throughput dose response assay for inhibitors of ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 (ASAP1). (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1K3	Abcam HeLa ASAP1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists