ASAP3

Summary

ASAP3 (ArfGAP with SH3 domain, ankyrin repeat and PH domain 3, HGNC:14987) is a protein-coding gene on chromosome 1p36.12, encoding Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 (Q8TDY4). Promotes cell proliferation.

This gene encodes a member of a subfamily of ADP-ribosylation factor(Arf) GTPase-activating proteins that contain additional ankyrin repeat and pleckstrin homology domains. The Arf GAP domain of this protein catalyzes the hydrolysis of GTP bound to Arf proteins. The encoded protein promotes cell differentiation and migration and has been implicated in cancer cell invasion. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55616 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 152 total — 2 pathogenic
• GTEx eGene: eQTL in 37 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.86 (unconstrained)
• MANE Select transcript: NM_017707
• Notable: 152 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14987
Approved symbol	ASAP3
Name	ArfGAP with SH3 domain, ankyrin repeat and PH domain 3
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20199, UPLC1, CENTB6
Ensembl gene	ENSG00000088280
Ensembl biotype	protein_coding
OMIM	616594
Entrez	55616

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 23 nonsense_mediated_decay, 18 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000336689

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 2, TSL 4: 2, TSL 5: 3

ENST00000336689, ENST00000437606, ENST00000449467, ENST00000465372, ENST00000475814, ENST00000478858, ENST00000484418, ENST00000492982, ENST00000495646, ENST00000530874, ENST00000608765, ENST00000711425, ENST00000711426, ENST00000711427, ENST00000857995, ENST00000857996, ENST00000857997, ENST00000931115, ENST00000948795, ENST00000948796, ENST00000948797, ENST00001004261, ENST00001004262, ENST00001050960, ENST00001050963, ENST00001050964, ENST00001050968, ENST00001050969, ENST00001050970, ENST00001050971, ENST00001050972, ENST00001050974, ENST00001050975, ENST00001077197, ENST00001077198, ENST00001077199, ENST00001077200, ENST00001077201, ENST00001077202, ENST00001112662, ENST00001112663, ENST00001122567, ENST00001122568, ENST00001145551

RefSeq mRNA: 2 — MANE Select: NM_017707 NM_001143778, NM_017707

CCDS: CCDS235, CCDS44087

Canonical transcript exons

ENST00000336689 — 25 exons

Exon	Start	End
ENSE00001362141	23428563	23429930
ENSE00001844250	23484005	23484179
ENSE00003467913	23433077	23433272
ENSE00003483085	23437130	23437320
ENSE00003492697	23434254	23434369
ENSE00003492732	23431035	23431125
ENSE00003496864	23441102	23441211
ENSE00003518474	23433626	23433693
ENSE00003533775	23456122	23456194
ENSE00003535431	23455881	23456026
ENSE00003536072	23434533	23434618
ENSE00003541802	23442186	23442271
ENSE00003549086	23433425	23433532
ENSE00003572774	23436560	23436654
ENSE00003609137	23452697	23452771
ENSE00003609752	23436911	23437044
ENSE00003614132	23442501	23442612
ENSE00003615423	23441655	23441730
ENSE00003627765	23439161	23439230
ENSE00003630209	23431696	23431918
ENSE00003648973	23437424	23437472
ENSE00003662257	23435851	23436028
ENSE00003663228	23438747	23438834
ENSE00003672177	23441387	23441473
ENSE00003788989	23451479	23451528

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0638 / max 109.8969, expressed in 1318 samples.

Highest expression (Bgee): ovary, skin of leg, zone of skin, skin of abdomen, sural nerve.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASAP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 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 41 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	2.4e-75	+0.46	1:23483867:T:C
Thyroid	eqtl	2.4e-52	+0.53	1:23484995:T:C
Cells Cultured fibroblasts	eqtl	4.3e-41	+0.22	1:23479282:AGAG:A
Heart Left Ventricle	eqtl	1.1e-30	+0.46	1:23483867:T:C
Heart Atrial Appendage	eqtl	1.1e-23	+0.44	1:23479282:AGAG:A
Adipose Subcutaneous	eqtl	1.2e-21	+0.27	1:23484568:C:T
Adrenal Gland	eqtl	5.0e-16	+0.38	1:23459710:C:T
Breast Mammary Tissue	eqtl	6.3e-12	+0.27	1:23484995:T:C
Brain Frontal Cortex BA9	eqtl	2.3e-11	-0.29	1:23493118:T:C
Brain Cortex	eqtl	2.0e-10	-0.29	1:23493118:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-10	+0.20	1:23469511:G:A
Testis	eqtl	2.8e-10	+0.36	1:23474608:T:C
Adipose Visceral Omentum	eqtl	4.6e-10	+0.19	1:23484995:T:C
Skin Sun Exposed Lower leg	eqtl	8.7e-10	+0.20	1:23468421:A:G
Esophagus Muscularis	eqtl	1.2e-09	+0.17	1:23483867:T:C
Lung	eqtl	2.0e-09	+0.23	1:23484568:C:T
Artery Tibial	eqtl	9.8e-09	-0.19	1:23503767:C:T
Nerve Tibial	eqtl	1.0e-08	-0.18	1:23501228:G:T
Pituitary	eqtl	4.5e-08	+0.29	1:23424647:G:T
Spleen	eqtl	1.5e-06	-0.51	1:23417663:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
10976	6.0638	1318

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right ovary	UBERON:0002118	96.25	gold quality
left ovary	UBERON:0002119	95.73	gold quality
ovary	UBERON:0000992	95.44	gold quality
skin of leg	UBERON:0001511	94.79	gold quality
zone of skin	UBERON:0000014	94.77	gold quality
skin of abdomen	UBERON:0001416	94.71	gold quality
sural nerve	UBERON:0015488	94.14	gold quality
apex of heart	UBERON:0002098	94.09	gold quality
right adrenal gland	UBERON:0001233	93.69	gold quality
lower esophagus mucosa	UBERON:0035834	93.55	gold quality
right adrenal gland cortex	UBERON:0035827	93.46	gold quality
minor salivary gland	UBERON:0001830	93.20	gold quality
left adrenal gland cortex	UBERON:0035825	93.16	gold quality
mucosa of stomach	UBERON:0001199	93.14	gold quality
saliva-secreting gland	UBERON:0001044	93.03	gold quality
tibial nerve	UBERON:0001323	92.98	gold quality
left adrenal gland	UBERON:0001234	92.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.84	gold quality
vagina	UBERON:0000996	92.61	gold quality
adrenal gland	UBERON:0002369	92.30	gold quality
ectocervix	UBERON:0012249	92.26	gold quality
gastrocnemius	UBERON:0001388	92.14	gold quality
endocervix	UBERON:0000458	92.03	gold quality
left uterine tube	UBERON:0001303	91.98	gold quality
adrenal tissue	UBERON:0018303	91.95	gold quality
muscle of leg	UBERON:0001383	91.72	gold quality
skeletal muscle tissue	UBERON:0001134	91.56	gold quality
right lobe of thyroid gland	UBERON:0001119	91.51	gold quality
prostate gland	UBERON:0002367	91.49	gold quality
thyroid gland	UBERON:0002046	91.48	gold quality
uterine cervix	UBERON:0000002	91.47	gold quality
left lobe of thyroid gland	UBERON:0001120	91.43	gold quality
fundus of stomach	UBERON:0001160	90.51	gold quality
right atrium auricular region	UBERON:0006631	90.48	gold quality
body of stomach	UBERON:0001161	90.43	gold quality
heart left ventricle	UBERON:0002084	90.43	gold quality
body of uterus	UBERON:0009853	90.37	gold quality
calcaneal tendon	UBERON:0003701	90.21	gold quality
esophagus mucosa	UBERON:0002469	90.20	gold quality
thoracic mammary gland	UBERON:0005200	90.05	gold quality
stomach	UBERON:0000945	90.01	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.00	gold quality
esophagus	UBERON:0001043	89.84	gold quality
ventricular zone	UBERON:0003053	89.84	gold quality
myometrium	UBERON:0001296	89.81	gold quality
heart	UBERON:0000948	89.71	gold quality
lower esophagus	UBERON:0013473	89.57	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.56	gold quality
adipose tissue	UBERON:0001013	89.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.33	gold quality
muscle tissue	UBERON:0002385	89.30	gold quality
omental fat pad	UBERON:0010414	88.80	gold quality
placenta	UBERON:0001987	88.75	gold quality
adenohypophysis	UBERON:0002196	88.53	gold quality
mucosa of transverse colon	UBERON:0004991	88.10	gold quality
body of pancreas	UBERON:0001150	87.89	gold quality
pituitary gland	UBERON:0000007	87.69	gold quality
urinary bladder	UBERON:0001255	87.63	gold quality
right coronary artery	UBERON:0001625	87.55	gold quality
fallopian tube	UBERON:0003889	87.51	gold quality
adult mammalian kidney	UBERON:0000082	87.39	gold quality
transverse colon	UBERON:0001157	87.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.07	gold quality
amygdala	UBERON:0001876	86.71	gold quality
temporal lobe	UBERON:0001871	86.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.60	gold quality
stromal cell of endometrium	CL:0002255	86.45	gold quality
colon	UBERON:0001155	86.42	gold quality
ganglionic eminence	UBERON:0004023	86.41	gold quality
upper lobe of left lung	UBERON:0008952	86.38	gold quality
smooth muscle tissue	UBERON:0001135	86.34	gold quality
tonsil	UBERON:0002372	86.22	gold quality
metanephros cortex	UBERON:0010533	86.14	gold quality
left coronary artery	UBERON:0001626	85.97	gold quality
right lung	UBERON:0002167	85.93	gold quality
kidney	UBERON:0002113	85.87	gold quality
lung	UBERON:0002048	85.68	gold quality
multicellular organism	UBERON:0000468	85.52	gold quality
right testis	UBERON:0004534	85.32	gold quality
ascending aorta	UBERON:0001496	85.30	gold quality
descending thoracic aorta	UBERON:0002345	85.29	gold quality
substantia nigra	UBERON:0002038	85.25	gold quality
thoracic aorta	UBERON:0001515	85.22	gold quality
right lobe of liver	UBERON:0001114	84.89	gold quality
intestine	UBERON:0000160	84.82	gold quality
cortex of kidney	UBERON:0001225	84.77	gold quality
caudate nucleus	UBERON:0001873	84.77	gold quality
left testis	UBERON:0004533	84.70	gold quality
colonic epithelium	UBERON:0000397	84.69	gold quality
testis	UBERON:0000473	84.69	gold quality
gall bladder	UBERON:0002110	84.58	gold quality
pancreas	UBERON:0001264	84.26	gold quality
popliteal artery	UBERON:0002250	84.13	gold quality
tibial artery	UBERON:0007610	84.13	gold quality
anterior cingulate cortex	UBERON:0009835	84.01	gold quality
putamen	UBERON:0001874	83.77	gold quality
hypothalamus	UBERON:0001898	83.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.55	gold quality
Ammon’s horn	UBERON:0001954	83.20	gold quality
nucleus accumbens	UBERON:0001882	83.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.47

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Vagina	tissue	31.5	not detected
Skin 1	tissue	25.9	not detected
Spinal cord	tissue	22.0
Ovary	tissue	20.8	not detected
Pituitary gland	tissue	17.9
Medulla oblongata	tissue	17.4
Substantia nigra	tissue	17.0
Midbrain	tissue	16.5
Thalamus	tissue	15.7
Corpus callosum	tissue	15.7
Superior colliculi	tissue	15.6
Periaqueductal gray	tissue	15.4
Pons	tissue	14.5
Hypothalamus	tissue	14.5
Amygdala	tissue	11.3
Parathyroid gland	tissue	11.0	low
Tongue	tissue	10.9
Hippocampal formation	tissue	10.9
Salivary gland	tissue	10.8	not detected
Septum	tissue	10.8
Skeletal muscle	tissue	10.7	medium
Putamen	tissue	10.4
Ventral forebrain	tissue	10.3
Locus coeruleus	tissue	10.1
Esophagus	tissue	9.7	not detected
Basal ganglia	tissue	9.3	not detected
Cerebral cortex	tissue	9.0	low
Insular cortex	tissue	9.0
Thyroid gland	tissue	8.8	not detected
Prostate	tissue	8.5	low
Retrosplenial cortex	tissue	8.5
Adrenal gland	tissue	8.2	not detected
Motor cortex	tissue	8.0
Entorhinal cortex	tissue	8.0
Hippocampus	tissue	7.8	low
Temporal cortex	tissue	7.8
Prefrontal cortex	tissue	7.7
Heart muscle	tissue	7.7	medium
Cervix	tissue	7.6	not detected
Seminal vesicle	tissue	7.5	not detected
Olfactory bulb	tissue	7.5
Placenta	tissue	7.4	not detected
Retrosplenial and cingulate cortex	tissue	7.3
Somatosensory cortex	tissue	7.1
Choroid plexus	tissue	6.9
Occipital cortex	tissue	6.9
Cerebellum	tissue	6.7	not detected
Colon	tissue	6.6	low
Postcentral gyrus	tissue	6.2
Pancreas	tissue	6.1	not detected
Breast	tissue	6.0	not detected
Stomach 1	tissue	6.0	low
Lung	tissue	5.8	medium
Testis	tissue	5.7	not detected
Nucleus accumbens	tissue	5.6
Fallopian tube	tissue	5.6	not detected
Smooth muscle	tissue	5.5	medium
Adipose tissue	tissue	5.3	not detected
Endometrium 1	tissue	5.3	not detected
Gallbladder	tissue	4.8	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Ventral spinal cord (22.0), Dorsal spinal cord (20.1), Area postrema (16.3), White matter (15.7), Blood vessel (14.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ASAP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 40 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-7702	99.06	65.95	698
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-5007-5P	97.95	64.71	614
HSA-MIR-8089	97.74	66.21	1698

Functional genomics

gnomAD constraint: pLI 1.6e-20, LOEUF 0.864, missense Z 1.82 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000336689 — one region, missense o/e 0.87.

Literature-anchored findings (GeneRIF, showing 11)

• ACAP4 is involved in ARF6-mediated cell migration. (PMID:16737952)
• ASAP3 functions nonredundantly with ASAP1 to control cell movement and may have a role in cancer cell invasion. (PMID:18400762)
• The ArfGAP catalytic mechanism and shows a glutamine from Arf6 and an arginine fingerASAP3 as the important catalytic residues; unexpectedly the structure shows a calcium ion, liganded by both proteins in the complex interface. (PMID:20510928)
• ACAP4 protein cooperates with Grb2 protein to orchestrate epidermal growth factor-stimulated integrin beta1 recycling in cell migration (PMID:22027826)
• Phosphorylation of the N-terminal region of ACAP4 (named the Bin, Amphiphysin, and RSV161/167[BAR] domain at Tyr34) is necessary for epidermal growth factor (EGF)-elicited membrane remodeling. (PMID:23776207)
• ). These data indicate that ASAP3 is elevated in NSCLC and may contribute to cancer development and patients’ poor clinical outcome, which is possibly due to its critical roles in regulating cancer invasion. (PMID:24078447)
• The data, for the first time, link ASAP3 with ACTG1 in the regulation of cytoskeletal maintenance and cell motility (PMID:24284654)
• Results show that ASAP3 was amplified in colorectal cancer (CRC) tissues, and its upregulation was associated with poor prognosis of patients with CRC. Also, it promoted growth of colon tumors, and accelerated cell invasion and migration through its binding to NEMO. These results suggest that ASAP3 acts as an oncogene. (PMID:28502111)
• ARF6 GTPase-activating protein ACAP4 regulates CCL18-elicited breast cancer cell migration via the acetyltransferase PCAF-mediated acetylation. CCL18 stimulation elicited breast cancer cell migration and invasion via PCAF-dependent acetylation. (PMID:30395269)
• MiR-143-3p acts as an anti-oncogene by downregulating ITGA6/ASAP3 protein expression and could offer new insight into potential therapeutic targets for CRC. (PMID:30536996)
• ACAP4 physically interacts with CrkII. Functional characterization showed that the interaction is required for the recruitment of ACAP4 to the plasma membrane where ACAP4 functions to regulate the recycling of the signal transducer integrin beta1. (PMID:31182282)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asap3	ENSMUSG00000036995
rattus_norvegicus	Asap3	ENSRNOG00000049714

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), 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), 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:2684986) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vocalization	1
abnormal coat/hair pigmentation	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
Macaca fascicularis	Q4R4C9	97.1%	Diamond
Pongo abelii	Q5R787	97.1%	Diamond
Bos taurus	O97902	95.9%	Diamond
Xenopus laevis	Q6NRL1	89.5%	Diamond
Arabidopsis thaliana	Q8LFN9	86.9%	Diamond
Gallus gallus	Q5F413	74.7%	Diamond
Xenopus tropicalis	Q28CM8	71.6%	Diamond
Drosophila melanogaster	Q95RG8	59.5%	Diamond
Saccharomyces cerevisiae S288C	P35197	58.5%	Diamond
Schizosaccharomyces pombe 972h-	Q10165	58.0%	Diamond
Caenorhabditis elegans	Q09531	54.7%	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
E2F2	protein-coding	1870
ID3	protein-coding	3399
TCEA3	protein-coding	6920
HNRNPR	protein-coding	10236
ZNF436-AS1	ncRNA	148898
ZNF436	protein-coding	80818
MDS2	ncRNA	259283
LINC01355	ncRNA	100996511

Protein

Protein identifiers

Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 — Q8TDY4 (reviewed: Q8TDY4)

Alternative names: Development and differentiation-enhancing factor-like 1, Protein up-regulated in liver cancer 1

All UniProt accessions (9): A0AAA9YHE6, A0AAA9YHL1, A0AAA9YHX1, E9PS98, Q8TDY4, H0YE36, H0YEB0, H0YER8, V9GY49

UniProt curated annotations — full annotation on UniProt →

Function. Promotes cell proliferation.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in primary hepatocarcinoma. Detected in lung, liver and blood leukocytes.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TDY4-1	1	yes
Q8TDY4-2	2
Q8TDY4-3	3

RefSeq proteins (2): NP_001137250, NP_060177* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	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
IPR028775	BAR_ASAP3	Domain
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
IPR047006	ASAP3_ArfGap	Domain

Pfam: PF00169, PF01412, PF12796, PF16746

UniProt features (48 total): helix 14, turn 7, strand 7, sequence conflict 4, compositionally biased region 3, domain 2, splice variant 2, sequence variant 2, repeat 2, coiled-coil region 2, chain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
2B0O	Crystal structure of UPLC1 GAP domain	X-RAY DIFFRACTION	2.06
9JIH	Crystal structure of BAR domain of ACAP4	X-RAY DIFFRACTION	2.8
3LVQ	The crystal structure of ASAP3 in complex with Arf6 in transition state	X-RAY DIFFRACTION	3.38
3LVR	The crystal structure of ASAP3 in complex with Arf6 in transition state soaked with …	X-RAY DIFFRACTION	3.38

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDY4-F1	74.62	0.48

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoplasm

Antibody reliability (HPA): IH approved · IF supported

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: 101 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOCC_RUFFLE, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CHANDRAN_METASTASIS_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, DOANE_RESPONSE_TO_ANDROGEN_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY

GO Biological Process (3): cell migration (GO:0016477), positive regulation of GTPase activity (GO:0043547), regulation of stress fiber assembly (GO:0051492)

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

GO Cellular Component (4): ruffle (GO:0001726), cytoplasm (GO:0005737), plasma membrane (GO:0005886), focal adhesion (GO:0005925)

GO top-level categories

19 GO namespaces:

Category	Terms
GTPase activity	2
cell motility	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of actomyosin structure organization	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane	1
cell periphery	1
cell-substrate junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
cell migration	BP	mutant phenotype
positive regulation of GTPase activity	BP	direct assay
regulation of stress fiber assembly	BP	mutant phenotype
focal adhesion	CC	direct assay
ruffle	CC	direct assay
GTPase activator activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 564 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASAP3	ARF6	P26438	540
ASAP3	MRPL18	Q9H0U6	471
ASAP3	TULP3	O75386	455
ASAP3	CNKSR1	Q969H4	445
ASAP3	TRPT1	Q86TN4	441
ASAP3	PLEKHA4	Q9H4M7	438
ASAP3	TMEM276	P0DTL5	438
ASAP3	RASSF9	O75901	428
ASAP3	ARFIP1	P53367	409
ASAP3	RASA1	P20936	387
ASAP3	STK26	Q9P289	387
ASAP3	ARF5	P26437	375
ASAP3	SLC9D1	Q6UWJ1	370
ASAP3	HTR6	P50406	362
ASAP3	PSMD2	Q13200	357
ASAP3	NOTCH1	P46531	357

IntAct

Human interaction partners of ASAP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
CRK	physical association	0.770	4
NHERF4	physical association	0.560	6
REL	physical association	0.560	6
TCF4	physical association	0.560	3
TEPSIN	physical association	0.560	3
TFCP2	physical association	0.560	3
UBE3A	physical association	0.560	3
GOLGA2	physical association	0.400	1
ASAP2	association	0.350	1
MTNR1A	physical association	0.000	1

BioGRID (38 interactions; top human partners by supporting records): CRK (Two-hybrid; 3 records), ACAD11 (Affinity Capture-MS; 2 records), ASAP1 (Affinity Capture-MS; 2 records), ASAP2 (Affinity Capture-MS; 2 records), BACH1 (Affinity Capture-MS; 2 records), ELP2 (Affinity Capture-MS; 2 records), GOLGA2 (Affinity Capture-MS; 2 records), HSPA1A (Affinity Capture-MS; 2 records), KIAA1161 (Affinity Capture-MS; 2 records), PDZD3 (Two-hybrid; 2 records), REL (Two-hybrid; 2 records), CRKL (Affinity Capture-MS), ENTHD2 (Two-hybrid), HRAS (Proximity Label-MS), IKBKG (Affinity Capture-Western)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
EGFR	“up-regulates activity”	ASAP3	phosphorylation
ASAP3	“up-regulates activity”	ARHGEF6	binding
STK26	“up-regulates activity”	ASAP3	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for ASAP3: 152 ClinVar records (2 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	112
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3247719	NC_000001.10:g.(?23395012)(24673151_?)del	Pathogenic	criteria provided, single submitter	1
4888366	GRCh38/hg38 1p36.12-36.11(chr1:23200857-23914935)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ASAP3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 2,442):

Position(s)	Effect	Δscore	Sites
1:23431927	acceptor_gain	1.0000
1:23433273–23433274	acceptor_loss	1.0000	6
1:23433381	donor_gain	1.0000
1:23433423–23433424	donor_loss	1.0000	5
1:23434252–23434253	donor_loss	1.0000	4
1:23434272–23434274	donor_gain	1.0000	2
1:23434370–23434371	acceptor_loss	1.0000	6
1:23434384	acceptor_gain	1.0000
1:23434388	acceptor_gain	1.0000
1:23434531–23434532	donor_loss	1.0000	5

AlphaMissense

1,467 missense substitutions predicted likely pathogenic (of 5,911 scored), across 418 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
F363	8	0.976	0.998
H336	8	0.975	0.996
D443	8	0.971	0.985
F374	8	0.969	0.999
N391	8	0.953	0.989
H468	8	0.951	0.985
D484	8	0.948	0.981
N499	8	0.946	0.991
N438	8	0.934	0.990
F99	8	0.922	0.993
F226	8	0.921	0.987
F105	8	0.892	0.980
F607	8	0.885	0.984
D228	8	0.864	0.961
D17	8	0.854	0.945
F27	8	0.843	0.964
F502	8	0.819	0.973
H627	8	0.815	0.904
W385	7	0.993	0.999
W451	7	0.990	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000194
Glioblastoma Multiforme (validation)	favorable	0.000483

Disease associations

OMIM: gene MIM:616594 | disease phenotypes: MIM:105650

GenCC curated gene-disease

Mondo (1): Diamond-Blackfan anemia (MONDO:0015253)

Orphanet (1): Diamond-Blackfan anemia (Orphanet:124)

GWAS associations

6 associations:

Study	Trait	p-value
GCST90013407_94	Liver enzyme levels (gamma-glutamyl transferase)	1e-27
GCST010244_202	Triglyceride levels	3e-11
GCST010245_64	LDL cholesterol levels	2e-9
GCST002221_29	Cholesterol, total	6e-9
GCST004235_78	Total cholesterol levels	1e-7
GCST90026414_2	Severe insulin-resistant type 2 diabetes	5e-7

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D029503	Anemia, Diamond-Blackfan	C15.378.050.085.080.090; C15.378.050.750.500; C15.378.190.223.500.500.090; C16.320.077.090

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
entinostat	increases expression, affects cotreatment	2
Arsenic	decreases expression, increases abundance, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	affects cotreatment, 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
ICG 001	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Rotenone	decreases expression	1
Selenium	increases expression	1
T-2 Toxin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8ZI	Ubigene HEK293 ASAP3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

38 trials:

NCT	Phase	Status	Title
NCT00673608	Phase 4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT00235391	Phase 3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
NCT00001962	Phase 2	TERMINATED	A Study to Determine Whether Therapy With Daclizumab Will Benefit Patients With Bone Marrow Failure
NCT00011505	Phase 2	COMPLETED	Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia
NCT00301834	Phase 2	COMPLETED	Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders
NCT00957931	Phase 2	COMPLETED	Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
NCT01529827	Phase 2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT02386267	Phase 2	UNKNOWN	L-leucine in Diamond Blackfan Anemia Patients
NCT02512679	Phase 2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT03333486	Phase 2	TERMINATED	Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
NCT04099966	Phase 2	RECRUITING	AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
NCT04965597	Phase 2	COMPLETED	Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)
NCT01586455	Phase 1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT01917708	Phase 1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT00176852	Phase 2/3	COMPLETED	Stem Cell Transplant for Hemoglobinopathy
NCT00176878	Phase 2/3	COMPLETED	Stem Cell Transplant for Bone Marrow Failure Syndromes
NCT00305708	Phase 1/2	COMPLETED	Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
NCT01362595	Phase 1/2	COMPLETED	Pilot Phase I/II Study of Amino Acid Leucine in Treatment of Patients With Transfusion-Dependent Diamond Blackfan Anemia
NCT01419704	Phase 1/2	WITHDRAWN	Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies
NCT01464164	Phase 1/2	TERMINATED	Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
NCT01966367	Phase 1/2	ACTIVE_NOT_RECRUITING	CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation
NCT02065869	Phase 1/2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03513328	Phase 1/2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT03653338	Phase 1/2	RECRUITING	T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias
NCT03733249	Phase 1/2	TERMINATED	Long Term Follow-up Study for Patients Enrolled on the BP-004 Clinical Study
NCT03966053	Phase 1/2	TERMINATED	The Use of Trifluoperazine in Transfusion Dependent DBA
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT00244010	Not specified	COMPLETED	Partially Matched Stem Cell Transplantation for Patients With Refractory Severe Aplastic Anemia or Refractory Cytopenias
NCT00290628	Not specified	TERMINATED	Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer
NCT01114776	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Pilot Study
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT01758042	Not specified	COMPLETED	Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders
NCT01913548	Not specified	COMPLETED	Multi-Center Study of Iron Overload: Survey Study (MCSIO)
NCT02179359	Not specified	TERMINATED	Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT07186179	Not specified	RECRUITING	Mobilization of CD34+ Peripheral Blood Stem Cells in Patients With Diamond Blackfan Anemia Syndrome (DBAS)