ASAP2

Summary

ASAP2 (ArfGAP with SH3 domain, ankyrin repeat and PH domain 2, HGNC:2721) is a protein-coding gene on chromosome 2p25.1, encoding Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 (O43150). Activates the small GTPases ARF1, ARF5 and ARF6.

This gene encodes a multidomain protein containing an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology (PH) domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal Src homology 3 (SH3) domain. The protein localizes in the Golgi apparatus and at the plasma membrane, where it colocalizes with protein tyrosine kinase 2-beta (PYK2). The encoded protein forms a stable complex with PYK2 in vivo. This interaction appears to be mediated by binding of its SH3 domain to the C-terminal proline-rich domain of PYK2. The encoded protein is tyrosine phosphorylated by activated PYK2. It has catalytic activity for class I and II ArfGAPs in vitro, and can bind the class III Arf ARF6 without immediate GAP activity. The encoded protein is believed to function as an ARF GAP that controls ARF-mediated vesicle budding when recruited to Golgi membranes. In addition, it functions as a substrate and downstream target for PYK2 and SRC, a pathway that may be involved in the regulation of vesicular transport. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8853 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 185 total
• GTEx eGene: eQTL in 33 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_003887
• Notable: 185 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2721
Approved symbol	ASAP2
Name	ArfGAP with SH3 domain, ankyrin repeat and PH domain 2
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0400, PAP, SHAG1, CENTB3
Ensembl gene	ENSG00000151693
Ensembl biotype	protein_coding
OMIM	603817
Entrez	8853

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000281419

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 4: 2

ENST00000281419, ENST00000315273, ENST00000471687, ENST00000484590, ENST00000491413, ENST00000641030, ENST00000865541, ENST00000865542, ENST00000938589, ENST00000938590, ENST00000992778, ENST00000992779, ENST00000992780, ENST00000992781, ENST00001106875, ENST00001106876, ENST00001125356, ENST00001144071

RefSeq mRNA: 2 — MANE Select: NM_003887 NM_001135191, NM_003887

CCDS: CCDS1661, CCDS46224

Canonical transcript exons

ENST00000281419 — 28 exons

Exon	Start	End
ENSE00001001187	9380741	9380808
ENSE00001001188	9344731	9344800
ENSE00001001189	9376908	9376993
ENSE00001001190	9356179	9356345
ENSE00001001191	9320288	9320337
ENSE00001001195	9391062	9391196
ENSE00001001196	9334738	9334813
ENSE00001001197	9318524	9318598
ENSE00001001198	9358756	9358889
ENSE00001001200	9327826	9327911
ENSE00001001202	9368425	9368519
ENSE00001001204	9297300	9297445
ENSE00001001206	9378944	9379059
ENSE00001001208	9374755	9374944
ENSE00001001210	9323121	9323250
ENSE00001001211	9350808	9350895
ENSE00001001212	9385245	9385358
ENSE00001001213	9279317	9279389
ENSE00001070568	9335093	9335179
ENSE00001070573	9344532	9344635
ENSE00001870668	9403253	9405678
ENSE00003487277	9400023	9400072
ENSE00003510253	9400742	9400830
ENSE00003510547	9393482	9393647
ENSE00003531223	9356047	9356095
ENSE00003598933	9401274	9401396
ENSE00003626269	9388294	9388546
ENSE00003850277	9206812	9207230

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.3530 / max 339.7933, expressed in 1676 samples.

Highest expression (Bgee): secondary oocyte, sperm, synovial joint, male germ cell, renal medulla.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASAP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 37 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	3.8e-37	+0.44	2:9284523:C:T
Artery Tibial	eqtl	2.2e-16	-0.23	2:9162889:T:C
Brain Spinal cord cervical c-1	eqtl	1.1e-15	-0.48	2:9306623:T:C
Artery Aorta	eqtl	2.2e-12	-0.27	2:9159570:T:A
Esophagus Muscularis	eqtl	5.1e-12	-0.25	2:9163467:A:G
Esophagus Gastroesophageal Junction	eqtl	1.1e-11	-0.35	2:9163467:A:G
Skin Sun Exposed Lower leg	eqtl	1.5e-10	+0.23	2:9402090:A:G
Thyroid	eqtl	3.3e-10	+0.31	2:9388672:T:C
Testis	sqtl	8.8e-08	+0.45	2:9296179:G:A
Skin Not Sun Exposed Suprapubic	eqtl	8.9e-08	+0.18	2:9178842:G:A
Nerve Tibial	eqtl	1.1e-07	-0.15	2:9292294:T:C
Adipose Visceral Omentum	eqtl	3.4e-07	+0.31	2:9373931:G:A
Adipose Subcutaneous	eqtl	1.4e-06	+0.23	2:9373931:G:A
Brain Cerebellum	eqtl	4.5e-06	+0.27	2:9403092:C:A
Brain Cortex	eqtl	2.7e-05	-0.29	2:9399534:T:C
Esophagus Mucosa	eqtl	3.7e-05	+0.17	2:9169646:A:G
Brain Hippocampus	eqtl	4.3e-05	+0.24	2:9275961:G:A
Cells Cultured fibroblasts	sqtl	6.2e-05	+0.58	2:9292680:C:T
Brain Putamen basal ganglia	eqtl	8.8e-05	-0.18	2:9340171:C:T
Adipose Subcutaneous	sqtl	1.1e-04	+0.55	2:9279454:G:A

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
18739	16.5446	1648
18740	6.4783	1493
18741	1.1471	765
18742	0.6041	371
18738	0.3234	153
18737	0.1733	38
18736	0.0822	18

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.31	gold quality
sperm	CL:0000019	97.21	gold quality
synovial joint	UBERON:0002217	96.72	gold quality
male germ cell	CL:0000015	95.33	gold quality
renal medulla	UBERON:0000362	94.89	gold quality
oocyte	CL:0000023	94.54	gold quality
amniotic fluid	UBERON:0000173	94.34	gold quality
cartilage tissue	UBERON:0002418	94.16	gold quality
buccal mucosa cell	CL:0002336	93.81	gold quality
adult organism	UBERON:0007023	93.71	gold quality
blood vessel layer	UBERON:0004797	93.34	gold quality
skin of hip	UBERON:0001554	93.31	gold quality
colonic mucosa	UBERON:0000317	93.04	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.04	gold quality
choroid plexus epithelium	UBERON:0003911	93.01	gold quality
calcaneal tendon	UBERON:0003701	92.79	gold quality
urethra	UBERON:0000057	92.13	gold quality
nephron tubule	UBERON:0001231	92.02	gold quality
saphenous vein	UBERON:0007318	91.88	gold quality
upper leg skin	UBERON:0004262	91.80	gold quality
sural nerve	UBERON:0015488	91.08	gold quality
tibia	UBERON:0000979	90.94	gold quality
colonic epithelium	UBERON:0000397	90.79	gold quality
layer of synovial tissue	UBERON:0007616	90.48	gold quality
oviduct epithelium	UBERON:0004804	90.47	gold quality
corpus epididymis	UBERON:0004359	90.45	gold quality
ganglionic eminence	UBERON:0004023	90.38	gold quality
upper arm skin	UBERON:0004263	90.34	gold quality
caput epididymis	UBERON:0004358	90.30	gold quality
parietal pleura	UBERON:0002400	90.21	gold quality
ventricular zone	UBERON:0003053	90.17	gold quality
kidney epithelium	UBERON:0004819	89.96	gold quality
pleura	UBERON:0000977	89.85	gold quality
cortical plate	UBERON:0005343	89.62	gold quality
visceral pleura	UBERON:0002401	89.54	gold quality
seminal vesicle	UBERON:0000998	89.44	gold quality
superficial temporal artery	UBERON:0001614	89.23	gold quality
substantia nigra pars compacta	UBERON:0001965	89.16	gold quality
endothelial cell	CL:0000115	89.15	gold quality
jejunal mucosa	UBERON:0000399	89.11	gold quality
tendon	UBERON:0000043	88.83	gold quality
embryo	UBERON:0000922	88.78	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.46	gold quality
epithelial cell of pancreas	CL:0000083	88.38	gold quality
ileal mucosa	UBERON:0000331	88.35	gold quality
nasal cavity epithelium	UBERON:0005384	88.00	gold quality
renal glomerulus	UBERON:0000074	87.98	gold quality
stromal cell of endometrium	CL:0002255	87.86	gold quality
kidney	UBERON:0002113	87.69	gold quality
testis	UBERON:0000473	87.66	gold quality
metanephric glomerulus	UBERON:0004736	87.65	gold quality
pylorus	UBERON:0001166	87.43	gold quality
palpebral conjunctiva	UBERON:0001812	87.39	gold quality
duodenum	UBERON:0002114	87.36	gold quality
ascending aorta	UBERON:0001496	87.16	gold quality
thoracic aorta	UBERON:0001515	87.09	gold quality
left testis	UBERON:0004533	87.06	gold quality
cervix squamous epithelium	UBERON:0006922	86.84	silver quality
right testis	UBERON:0004534	86.76	gold quality
descending thoracic aorta	UBERON:0002345	86.74	gold quality
germinal epithelium of ovary	UBERON:0001304	86.68	gold quality
metanephros	UBERON:0000081	86.64	gold quality
penis	UBERON:0000989	86.59	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.44	gold quality
trigeminal ganglion	UBERON:0001675	86.26	gold quality
epithelium of nasopharynx	UBERON:0001951	86.23	gold quality
lateral globus pallidus	UBERON:0002476	86.16	gold quality
right coronary artery	UBERON:0001625	86.13	gold quality
pancreatic ductal cell	CL:0002079	86.12	gold quality
lower lobe of lung	UBERON:0008949	86.10	silver quality
cervix epithelium	UBERON:0004801	86.05	gold quality
orbitofrontal cortex	UBERON:0004167	86.00	gold quality
eye	UBERON:0000970	85.98	gold quality
cauda epididymis	UBERON:0004360	85.81	gold quality
pons	UBERON:0000988	85.78	gold quality
aorta	UBERON:0000947	85.75	gold quality
postcentral gyrus	UBERON:0002581	85.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.71	gold quality
dorsal root ganglion	UBERON:0000044	85.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.70	gold quality
fallopian tube	UBERON:0003889	85.54	gold quality
parietal lobe	UBERON:0001872	85.33	gold quality
uterine cervix	UBERON:0000002	85.24	gold quality
rectum	UBERON:0001052	85.19	gold quality
vena cava	UBERON:0004087	85.19	silver quality
connective tissue	UBERON:0002384	85.17	gold quality
cortex of kidney	UBERON:0001225	85.13	gold quality
adipose tissue	UBERON:0001013	85.08	gold quality
adult mammalian kidney	UBERON:0000082	84.85	gold quality
hair follicle	UBERON:0002073	84.80	gold quality
superior frontal gyrus	UBERON:0002661	84.77	gold quality
popliteal artery	UBERON:0002250	84.67	gold quality
tibial artery	UBERON:0007610	84.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	84.61	gold quality
pericardium	UBERON:0002407	84.59	gold quality
sigmoid colon	UBERON:0001159	84.58	gold quality
decidua	UBERON:0002450	84.57	gold quality
CA1 field of hippocampus	UBERON:0003881	84.53	gold quality
squamous epithelium	UBERON:0006914	84.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	41.42
E-ANND-3	yes	4.91

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	61.4	medium
Occipital cortex	tissue	61.4
Somatosensory cortex	tissue	60.7
Motor cortex	tissue	52.5
Prefrontal cortex	tissue	51.9
Hippocampal formation	tissue	47.1
Entorhinal cortex	tissue	47.1
Retrosplenial cortex	tissue	47.0
Retrosplenial and cingulate cortex	tissue	46.7
Nucleus accumbens	tissue	44.5
Testis	tissue	43.7	high
Temporal cortex	tissue	43.1
Postcentral gyrus	tissue	40.8
Insular cortex	tissue	40.5
Locus coeruleus	tissue	35.1
Basal ganglia	tissue	34.9	medium
Putamen	tissue	34.4
Choroid plexus	tissue	32.7
Cerebellum	tissue	30.6	medium
Ventral forebrain	tissue	27.6
Thalamus	tissue	26.6
Superior colliculi	tissue	25.4
Pons	tissue	24.7
Substantia nigra	tissue	24.4
Amygdala	tissue	24.0
Stomach 1	tissue	22.9	medium
Kidney	tissue	22.2	high
Hippocampus	tissue	21.7	medium
Septum	tissue	21.4
Midbrain	tissue	21.1
Hypothalamus	tissue	20.9
Thyroid gland	tissue	17.9	medium
Colon	tissue	16.6	high
Medulla oblongata	tissue	16.1
Periaqueductal gray	tissue	16.0
Rectum	tissue	15.1	high
Spinal cord	tissue	15.1
Olfactory bulb	tissue	14.6
Smooth muscle	tissue	13.0	low
Frontal cortex	tissue	13.0
Duodenum	tissue	13.0	high
Small intestine	tissue	12.8	high
Skin 1	tissue	12.3	high
Endometrium 1	tissue	12.0	high
Adipose tissue	tissue	11.6	low
Cervix	tissue	10.8	medium
Fallopian tube	tissue	10.1	high
Placenta	tissue	9.8	high
Epididymis	tissue	9.4	high
Lung	tissue	9.4	medium
Gallbladder	tissue	9.4	medium
Parathyroid gland	tissue	9.3	medium
Heart muscle	tissue	9.0	not detected
Pituitary gland	tissue	8.8
Seminal vesicle	tissue	8.7	medium
Corpus callosum	tissue	8.6
Retina	tissue	8.2
Esophagus	tissue	8.2	high
Caudate putamen	tissue	8.2
Urinary bladder	tissue	7.9	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Caudate nucleus (47.2), Vermis (45.1), Cerebellar cortex (42.9), Flocculonodular lobe (42.6), Nuclei of the trapezoid body (40.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, VDR

miRNA regulators (miRDB)

Targeting ASAP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 170 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4682	100.00	68.89	1258
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585

Functional genomics

gnomAD constraint: pLI 0.998, LOEUF 0.465, missense Z 2.58 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000281419 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:9,207,105–9,358,876	359 / 598.1	0.60	no
2:9,358,877–9,403,324	652 / 698.9	0.93	no

Literature-anchored findings (GeneRIF, showing 2)

• regulates multiple cytokine and growth factor-activated signaling pathways by acting as a recruitment factor for adapter proteins (PMID:15231847)
• The novel driver gene ASAP2 is a potential druggable target in pancreatic cancer. (PMID:33605496)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	asap2a	ENSDARG00000010181
mus_musculus	Asap2	ENSMUSG00000052632
rattus_norvegicus	Asap2	ENSRNOG00000061519

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), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685438) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased prepulse inhibition	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3SX00	100.0%	Diamond
Pongo abelii	Q5R8C8	99.6%	Diamond
Macaca fascicularis	Q4R4C9	97.1%	Diamond
Arabidopsis thaliana	Q8LFN9	86.9%	Diamond
Gallus gallus	Q5F413	74.7%	Diamond
Xenopus tropicalis	Q28CM8	71.6%	Diamond
Saccharomyces cerevisiae S288C	P35197	58.5%	Diamond
Schizosaccharomyces pombe 972h-	Q10165	58.0%	Diamond
Caenorhabditis elegans	Q09531	54.7%	Diamond
Takifugu rubripes	Q1KKW7	51.9%	Diamond
Drosophila melanogaster	A1Z7A6	50.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ITGB1BP1	protein-coding	9270
CPSF3	protein-coding	51692
IAH1	protein-coding	285148
ADAM17	protein-coding	6868
YWHAQ	protein-coding	10971

Protein

Protein identifiers

Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 — O43150 (reviewed: O43150)

Alternative names: Development and differentiation-enhancing factor 2, Paxillin-associated protein with ARF GAP activity 3, Pyk2 C-terminus-associated protein

All UniProt accessions (2): A0A286YFG8, O43150

UniProt curated annotations — full annotation on UniProt →

Function. Activates the small GTPases ARF1, ARF5 and ARF6. Regulates the formation of post-Golgi vesicles and modulates constitutive secretion. Modulates phagocytosis mediated by Fc gamma receptor and ARF6. Modulates PXN recruitment to focal contacts and cell migration.

Subunit / interactions. Binds PXN, ARF1, ARF5, ARF6, PTK2B and SRC.

Subcellular location. Cytoplasm. Golgi apparatus. Golgi stack membrane. Cell membrane.

Tissue specificity. Detected in heart, brain, placenta, kidney, monocytes and pancreas.

Post-translational modifications. Phosphorylated on tyrosine residues by SRC and PTK2B.

Domain organisation. The conserved Arg-464 in the Arf-GAP domain probably becomes part of the active site of bound small GTPases and is necessary for GTP hydrolysis.

Induction. Up-regulated during monocytic maturation.

Isoforms (2)

UniProt ID	Names	Canonical?
O43150-1	1, PAPalpha	yes
O43150-2	2, PAPbeta

RefSeq proteins (2): NP_001128663, NP_003878* (*=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
IPR035677	ASAP2_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO_Zfn_sf	Homologous_superfamily
IPR037844	PH_ASAP	Domain
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR043593	ASAP	Family

Pfam: PF00169, PF01412, PF12796, PF14604, PF16746

UniProt features (21 total): domain 3, compositionally biased region 3, modified residue 3, region of interest 3, coiled-coil region 2, repeat 2, chain 1, splice variant 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43150-F1	75.71	0.52

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; plasma membrane

Antibody reliability (HPA): IH approved · IF supported

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 (3)

Type	Positions
Phosphoserine	701, 822
Phosphothreonine	903

Mutagenesis-validated functional residues (1)

Position	Phenotype
436	loss of arf-gap activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 223 (showing top): chr2p25, TGCACTT_MIR519C_MIR519B_MIR519A, ATACCTC_MIR202, BILD_SRC_ONCOGENIC_SIGNATURE, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_DN, CTAGGAA_MIR384, ONKEN_UVEAL_MELANOMA_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, CAIRO_HEPATOBLASTOMA_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, MODULE_98, LEF1_Q6, KEGG_ENDOCYTOSIS, GCM_CALM1, GTATGAT_MIR154_MIR487

GO Biological Process (1): positive regulation of GTPase activity (GO:0043547)

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

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), Golgi cisterna membrane (GO:0032580), cytoplasm (GO:0005737)

GO top-level categories

15 GO namespaces:

Category	Terms
GTPase activity	2
cellular anatomical structure	2
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
cation binding	1
binding	1
transition metal ion binding	1
cytoplasm	1
membrane	1
cell periphery	1
organelle membrane	1
Golgi cisterna	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
cytosol	CC	direct assay
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 726 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASAP2	PAPOLB	Q9NRJ5	755
ASAP2	ARF5	P26437	753
ASAP2	ARF6	P26438	666
ASAP2	PTK2B	Q14289	659
ASAP2	ARF1	P10947	633
ASAP2	RASA1	P20936	533
ASAP2	LPGAT1	Q92604	460
ASAP2	AGFG2	O95081	454
ASAP2	SELENOK	Q9Y6D0	451
ASAP2	PLEK2	Q9NYT0	443
ASAP2	ICA1	P78506	441
ASAP2	AFAP1L2	Q8N4X5	439
ASAP2	DENND6B	Q8NEG7	436
ASAP2	PLEK	P08567	419
ASAP2	ZDHHC6	Q9H6R6	393

IntAct

Human interaction partners of ASAP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

Partner	Interaction type	MIscore	Records
GRB2	physical association	0.750	2
SH3KBP1	physical association	0.670	1
PLCG1	physical association	0.600	3
NCK1	physical association	0.560	1
UBC	physical association	0.520	2
YES1	direct interaction	0.440	1
CBLB	physical association	0.400	1
CRK	physical association	0.400	1
FYN	physical association	0.400	1
H1-1	physical association	0.400	1
H1-5	physical association	0.400	1
PIK3R1	physical association	0.400	1
SRC	physical association	0.400	1
VILL	physical association	0.400	1
THSD7A	physical association	0.370	1
CLUAP1	association	0.350	2
ARHGAP12	association	0.350	1
ASAP3	association	0.350	1
KNDC1	association	0.350	1
NHSL3	association	0.350	1
ITSN1	physical association	0.000	1
TBRG4	physical association	0.000	1

BioGRID (52 interactions; top human partners by supporting records): SH3KBP1 (Two-hybrid; 4 records), GRB2 (Affinity Capture-MS; 3 records), NCK2 (Affinity Capture-MS; 3 records), ARHGAP12 (Affinity Capture-MS; 2 records), ASAP3 (Affinity Capture-MS; 2 records), PTK2B (Reconstituted Complex; 2 records), ADD3 (Co-fractionation), AGRN (Affinity Capture-MS), APC (Reconstituted Complex), C19orf35 (Affinity Capture-MS), CLUAP1 (Affinity Capture-MS), DHX40 (Co-fractionation), ELAVL1 (Affinity Capture-RNA), GAPDH (Cross-Linking-MS (XL-MS)), HEXIM1 (Affinity Capture-MS)

SIGNOR signaling

4 signaling interactions:

A	Effect	B	Mechanism
PTK2B	“up-regulates activity”	ASAP2	phosphorylation
ASAP2	“up-regulates activity”	ARF1	“gtpase-activating protein”
ASAP2	“up-regulates activity”	ARF6	“gtpase-activating protein”
ASAP2	“up-regulates activity”	ARF5	“gtpase-activating protein”

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ ASAP2-PTKB2 complex	2	ASAP2, PTK2B

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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
Regulation of signaling by CBL	6	175.2×	2e-10
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	152.7×	1e-08
Downstream signal transduction	6	134.3×	6e-10
Signaling by CSF1 (M-CSF) in myeloid cells	6	122.1×	7e-10
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	105.0×	6e-08
Signaling by SCF-KIT	5	73.0×	3e-07
FCGR3A-mediated phagocytosis	6	66.1×	2e-08
VEGFA-VEGFR2 Pathway	5	41.0×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	81.9×	1e-06
cell migration	5	14.6×	8e-04

Disease & clinical

Genetic variants

Variant evidence for ASAP2: 185 ClinVar records (0 pathogenic / likely pathogenic); 10 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	139
Likely benign	4
Benign	4

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 3,130):

Position(s)	Effect	Δscore	Sites
2:9279315–9279316	acceptor_loss	1.0000	4
2:9279390–9279391	donor_loss	1.0000	5
2:9297298–9297299	acceptor_loss	1.0000	4
2:9297446–9297447	donor_loss	1.0000	5
2:9320286–9320287	acceptor_loss	1.0000	6
2:9320338–9320339	donor_loss	1.0000	4
2:9323114–9323116	acceptor_gain	1.0000	2
2:9323119–9323120	acceptor_loss	1.0000	4
2:9323251–9323252	donor_loss	1.0000	5
2:9334732	acceptor_gain	1.0000

AlphaMissense

3,258 missense substitutions predicted likely pathogenic (of 6,645 scored), across 704 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M198	9	0.936	0.998
M519	9	0.933	0.986
H339	8	0.998	1.000
D17	8	0.997	1.000
F996	8	0.997	1.000
D438	8	0.996	0.999
H463	8	0.996	0.999
F965	8	0.996	1.000
F377	8	0.995	1.000
D479	8	0.995	0.999
D958	8	0.993	0.998
D978	8	0.992	0.998
F26	8	0.989	0.999
F366	8	0.988	1.000
N494	8	0.988	0.999
F10	8	0.987	1.000
D47	8	0.987	0.997
N433	8	0.986	0.999
D605	8	0.986	0.997
F1000	8	0.986	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.17e-07
Pancreatic Adenocarcinoma (validation)	unfavorable	1.81e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	9.24e-05

Disease associations

OMIM: gene MIM:603817 | disease phenotypes:

GWAS associations

10 associations:

Study	Trait	p-value
GCST007692_39	Chronic obstructive pulmonary disease	2e-10
GCST007269_40	Pulse pressure	7e-10
GCST005537_229	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	9e-10
GCST007096_170	Pulse pressure	7e-9
GCST008972_101	Urate levels	3e-8
GCST90025872_3	Chronic widespread musculoskeletal pain	3e-7
GCST008103_55	Bipolar disorder	8e-7
GCST008971_73	Urate levels	9e-7
GCST007097_5	Pulse pressure	3e-6
GCST000269_8	Multiple sclerosis	9e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004531	urate measurement
EFO:0010099	chronic widespread pain

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases mutagenesis, affects expression, affects methylation, decreases expression (+1 more)	6
Estradiol	decreases expression, affects cotreatment, increases expression, affects expression, affects binding	5
sodium arsenite	increases expression, affects methylation, decreases expression	3
bisphenol A	increases methylation, decreases methylation, increases expression, affects cotreatment	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Smoke	decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
lead acetate	increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
bicalutamide	increases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
K 7174	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.