ACAP3

Summary

ACAP3 (ArfGAP with coiled-coil, ankyrin repeat and PH domains 3, HGNC:16754) is a protein-coding gene on chromosome 1p36.33, encoding Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 3 (Q96P50). GTPase-activating protein for the ADP ribosylation factor family.

Predicted to enable GTPase activator activity and zinc ion binding activity. Predicted to act upstream of or within neuron migration and regulation of neuron projection development. Predicted to be located in endosome membrane and growth cone.

Source: NCBI Gene 116983 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 277 total — 79 pathogenic, 4 likely-pathogenic
• GTEx eGene: eQTL in 25 tissues, sQTL in 8 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.82 (unconstrained)
• MANE Select transcript: NM_030649
• Notable: 277 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16754
Approved symbol	ACAP3
Name	ArfGAP with coiled-coil, ankyrin repeat and PH domains 3
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1716
Ensembl gene	ENSG00000131584
Ensembl biotype	protein_coding
Entrez	116983

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 21 protein_coding, 14 nonsense_mediated_decay, 8 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000354700

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

ENST00000354700, ENST00000354980, ENST00000379037, ENST00000438966, ENST00000467278, ENST00000470659, ENST00000472541, ENST00000476572, ENST00000478065, ENST00000479108, ENST00000492936, ENST00000493992, ENST00000892719, ENST00000892720, ENST00000969099, ENST00000969100, ENST00000969101, ENST00000969102, ENST00000969103, ENST00000969104, ENST00000969105, ENST00000969106, ENST00000969107, ENST00000969108, ENST00000969109, ENST00000969110, ENST00000969111, ENST00001007889, ENST00001007890, ENST00001007891, ENST00001007892, ENST00001007893, ENST00001007894, ENST00001007895, ENST00001032004, ENST00001032005, ENST00001032006, ENST00001032007, ENST00001032008, ENST00001032009, ENST00001032010, ENST00001032011, ENST00001032012, ENST00001032013, ENST00001145699

RefSeq mRNA: 1 — MANE Select: NM_030649 NM_030649

CCDS: CCDS19

Canonical transcript exons

ENST00000354700 — 24 exons

Exon	Start	End
ENSE00001889322	1292391	1293708
ENSE00001927436	1307769	1307930
ENSE00003487130	1303162	1303281
ENSE00003495947	1294090	1294199
ENSE00003515599	1299831	1299905
ENSE00003517853	1300509	1300692
ENSE00003522844	1302922	1302975
ENSE00003524130	1294718	1294816
ENSE00003542543	1293823	1293933
ENSE00003547404	1298567	1298679
ENSE00003555901	1301988	1302046
ENSE00003556959	1304086	1304143
ENSE00003563439	1296425	1296633
ENSE00003576054	1295736	1295938
ENSE00003582087	1299345	1299356
ENSE00003582645	1295447	1295554
ENSE00003591650	1296015	1296109
ENSE00003615234	1297822	1297933
ENSE00003622960	1300158	1300202
ENSE00003640098	1298370	1298421
ENSE00003655822	1296211	1296280
ENSE00003673334	1299973	1300068
ENSE00003673746	1294402	1294628
ENSE00003689281	1298013	1298113

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2250 / max 64.1136, expressed in 1654 samples.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, cerebellum, frontal lobe.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACAP3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 33 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.6e-15	+0.21	1:1366427:AGTGTGATTGAATGAGT:A
Artery Tibial	eqtl	5.6e-12	-0.20	1:1395346:A:G
Artery Aorta	eqtl	3.0e-07	+0.21	1:1308516:C:T
Heart Atrial Appendage	eqtl	2.6e-06	+0.23	1:1352542:G:A
Cells Cultured fibroblasts	eqtl	3.6e-06	-0.18	1:1295039:T:C
Skin Sun Exposed Lower leg	sqtl	5.3e-06	-1.03	1:1296276:G:A
Nerve Tibial	eqtl	1.8e-05	+0.15	1:1327982:G:A
Heart Left Ventricle	eqtl	5.2e-05	+0.20	1:1306420:A:G
Pancreas	eqtl	6.4e-05	+0.23	1:1312114:T:C
Colon Sigmoid	eqtl	8.3e-05	+0.23	1:1363153:T:G
Adipose Subcutaneous	eqtl	3.6e-04	-0.18	1:1517976:T:C
Brain Cerebellar Hemisphere	sqtl	8.4e-04	-0.69	1:1303800:G:A
Esophagus Mucosa	eqtl	1.3e-03	+0.11	1:1312114:T:C
Lung	eqtl	1.3e-03	+0.16	1:1368047:ACT:A
Esophagus Muscularis	eqtl	1.4e-03	-0.15	1:1331945:G:GC
Testis	sqtl	1.4e-03	-1.32	1:1296276:G:A
Skin Not Sun Exposed Suprapubic	sqtl	1.5e-03	-0.26	1:1296939:G:A
Colon Transverse	eqtl	2.2e-03	+0.19	1:1307327:A:G
Esophagus Gastroesophageal Junction	eqtl	2.5e-03	-0.47	1:1375389:C:T
Stomach	eqtl	2.7e-03	+0.26	1:1307603:G:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
9748	4.0329	1551
9750	0.3796	198
9749	0.3047	171
9747	0.2748	122
201311	0.2330	95

Top tissues by expression

showing 100 of 243 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.74	gold quality
cerebellar hemisphere	UBERON:0002245	99.68	gold quality
cerebellar cortex	UBERON:0002129	99.64	gold quality
cerebellum	UBERON:0002037	99.15	gold quality
right frontal lobe	UBERON:0002810	98.80	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.36	gold quality
adenohypophysis	UBERON:0002196	98.28	gold quality
skin of abdomen	UBERON:0001416	98.08	gold quality
skin of leg	UBERON:0001511	97.99	gold quality
pituitary gland	UBERON:0000007	97.68	gold quality
ectocervix	UBERON:0012249	97.66	gold quality
nucleus accumbens	UBERON:0001882	97.65	gold quality
lower esophagus mucosa	UBERON:0035834	97.62	gold quality
anterior cingulate cortex	UBERON:0009835	97.61	gold quality
left uterine tube	UBERON:0001303	97.52	gold quality
body of uterus	UBERON:0009853	97.49	gold quality
putamen	UBERON:0001874	97.45	gold quality
apex of heart	UBERON:0002098	97.37	gold quality
cortical plate	UBERON:0005343	97.21	gold quality
endocervix	UBERON:0000458	97.15	gold quality
caudate nucleus	UBERON:0001873	97.09	gold quality
right ovary	UBERON:0002118	97.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.96	gold quality
amygdala	UBERON:0001876	96.95	gold quality
left ovary	UBERON:0002119	96.79	gold quality
lower esophagus	UBERON:0013473	96.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.60	gold quality
ganglionic eminence	UBERON:0004023	96.54	gold quality
minor salivary gland	UBERON:0001830	96.27	gold quality
upper arm skin	UBERON:0004263	96.27	gold quality
esophagus mucosa	UBERON:0002469	96.22	gold quality
esophagus	UBERON:0001043	96.16	gold quality
metanephros cortex	UBERON:0010533	96.07	gold quality
zone of skin	UBERON:0000014	95.95	gold quality
body of stomach	UBERON:0001161	95.78	gold quality
hypothalamus	UBERON:0001898	95.78	gold quality
tibial nerve	UBERON:0001323	95.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.66	gold quality
right atrium auricular region	UBERON:0006631	95.65	gold quality
spinal cord	UBERON:0002240	95.43	gold quality
transverse colon	UBERON:0001157	95.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.30	gold quality
mucosa of stomach	UBERON:0001199	95.24	gold quality
cardiac atrium	UBERON:0002081	94.92	gold quality
right adrenal gland	UBERON:0001233	94.90	gold quality
granulocyte	CL:0000094	94.86	gold quality
left adrenal gland cortex	UBERON:0035825	94.80	gold quality
brain	UBERON:0000955	94.72	gold quality
stromal cell of endometrium	CL:0002255	94.67	gold quality
right adrenal gland cortex	UBERON:0035827	94.67	gold quality
mouth mucosa	UBERON:0003729	94.62	gold quality
forebrain	UBERON:0001890	94.58	gold quality
right lobe of thyroid gland	UBERON:0001119	94.41	gold quality
heart left ventricle	UBERON:0002084	94.34	gold quality
left adrenal gland	UBERON:0001234	94.32	gold quality
neocortex	UBERON:0001950	94.26	gold quality
left lobe of thyroid gland	UBERON:0001120	94.25	gold quality
upper lobe of left lung	UBERON:0008952	94.22	gold quality
omental fat pad	UBERON:0010414	94.19	gold quality
Ammon’s horn	UBERON:0001954	94.15	gold quality
peritoneum	UBERON:0002358	94.10	gold quality
vagina	UBERON:0000996	94.09	gold quality
mucosa of transverse colon	UBERON:0004991	94.05	gold quality
uterine cervix	UBERON:0000002	93.97	gold quality
frontal cortex	UBERON:0001870	93.84	gold quality
cerebral cortex	UBERON:0000956	93.71	gold quality
cerebellar vermis	UBERON:0004720	93.69	gold quality
cardiac ventricle	UBERON:0002082	93.68	gold quality
right lung	UBERON:0002167	93.61	gold quality
adrenal cortex	UBERON:0001235	93.60	gold quality
right lobe of liver	UBERON:0001114	93.59	gold quality
stomach	UBERON:0000945	93.58	gold quality
spleen	UBERON:0002106	93.51	gold quality
sural nerve	UBERON:0015488	93.49	gold quality
right coronary artery	UBERON:0001625	93.40	gold quality
prefrontal cortex	UBERON:0000451	93.31	gold quality
saliva-secreting gland	UBERON:0001044	93.31	gold quality
small intestine	UBERON:0002108	93.24	gold quality
fundus of stomach	UBERON:0001160	93.21	gold quality
left coronary artery	UBERON:0001626	93.19	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.12	gold quality
gastrocnemius	UBERON:0001388	92.99	gold quality
body of pancreas	UBERON:0001150	92.92	gold quality
ascending aorta	UBERON:0001496	92.78	gold quality
temporal lobe	UBERON:0001871	92.78	gold quality
coronary artery	UBERON:0001621	92.75	gold quality
thoracic aorta	UBERON:0001515	92.69	gold quality
popliteal artery	UBERON:0002250	92.63	gold quality
muscle of leg	UBERON:0001383	92.62	gold quality
tibial artery	UBERON:0007610	92.62	gold quality
aorta	UBERON:0000947	92.54	gold quality
heart	UBERON:0000948	92.53	gold quality
adrenal gland	UBERON:0002369	92.53	gold quality
thyroid gland	UBERON:0002046	92.47	gold quality
gall bladder	UBERON:0002110	92.43	gold quality
corpus callosum	UBERON:0002336	92.39	gold quality
upper lobe of lung	UBERON:0008948	92.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	58.7
Hippocampus	tissue	48.8	not detected
Caudate putamen	tissue	45.8
Pituitary gland	tissue	43.3
Nucleus accumbens	tissue	42.8
Postcentral gyrus	tissue	37.2
Vagina	tissue	26.5	not detected
Putamen	tissue	26.1
Cerebral cortex	tissue	25.5	low
Insular cortex	tissue	25.5
Basal ganglia	tissue	24.9	not detected
Hippocampal formation	tissue	24.6
Temporal cortex	tissue	24.1
Amygdala	tissue	23.5
Entorhinal cortex	tissue	23.0
Motor cortex	tissue	22.5
Prefrontal cortex	tissue	22.0
Somatosensory cortex	tissue	21.4
Retrosplenial cortex	tissue	21.1
Ventral forebrain	tissue	21.0
Corpus callosum	tissue	20.8
Retrosplenial and cingulate cortex	tissue	20.1
Skin 1	tissue	19.8	low
Occipital cortex	tissue	19.7
Thalamus	tissue	18.6
Spinal cord	tissue	17.4
Midbrain	tissue	16.7
Locus coeruleus	tissue	16.5
Septum	tissue	16.5
Cerebellum	tissue	16.4	low
Substantia nigra	tissue	15.8
Superior colliculi	tissue	15.6
Hypothalamus	tissue	15.5
Pons	tissue	14.8
Medulla oblongata	tissue	14.7
Olfactory bulb	tissue	12.3
Periaqueductal gray	tissue	11.8
Skeletal muscle	tissue	11.3	low
Retina	tissue	11.2
Salivary gland	tissue	10.9	low
Choroid plexus	tissue	9.5
Bone marrow	tissue	8.5	not detected
Esophagus	tissue	6.9	low
Adipose tissue	tissue	6.3	not detected
Stomach 1	tissue	5.8	medium
Duodenum	tissue	5.6	high
Heart muscle	tissue	5.4	medium
Pancreas	tissue	5.4	medium
Tongue	tissue	5.4
Small intestine	tissue	5.3	high
Adrenal gland	tissue	5.1	high
Seminal vesicle	tissue	4.7	not detected
Spleen	tissue	4.5	not detected
Thymus	tissue	4.5
Colon	tissue	4.3	high
Endometrium 1	tissue	3.9	medium
Cervix	tissue	3.8	low
Prostate	tissue	3.7	low
Smooth muscle	tissue	3.5	not detected
Urinary bladder	tissue	3.4	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Posterior cingulate cortex (54.0), Caudate nucleus (51.3), Hippocampus, CA3 (50.9), Temporo-occipital transitional zone (50.7), Flocculonodular lobe (47.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ACAP3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 74 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-6837-5P	99.25	65.47	1632

Functional genomics

gnomAD constraint: pLI 1.64e-12, LOEUF 0.816, missense Z -1.95 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000354700 — one region, missense o/e 1.03.

Literature-anchored findings (GeneRIF, showing 3)

• minisatellite locus UPS29 can regulate an activity of CENTB5, SCNN1D and ACOT7 in nervous system cells. (PMID:19548526)
• Length Polymorphism and Methylation Status of UPS29 Minisatellite of the ACAP3 Gene as Molecular Biomarker of Epilepsy. Sex Differences in Seizure Types and Symptoms. (PMID:33276684)
• ACAP3 negatively regulated by HDAC2 inhibits the malignant development of papillary thyroid carcinoma cells. (PMID:39098591)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	acap3a	ENSDARG00000075990
danio_rerio	acap3b	ENSDARG00000099240
		ENSDARG00000115609
mus_musculus	Acap3	ENSMUSG00000029033
rattus_norvegicus	Acap3	ENSRNOG00000022307

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), 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:2153589) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body length	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
Oryctolagus cuniculus	Q6IVG4	98.1%	Diamond
Macaca fascicularis	Q4R4C9	97.1%	Diamond
Pongo abelii	Q5R787	97.1%	Diamond
Bos taurus	Q5EA00	95.1%	Diamond
Xenopus laevis	Q6NRL1	89.5%	Diamond
Drosophila mojavensis	B4K6T8	87.6%	Diamond
Gallus gallus	Q5ZK62	87.6%	Diamond
Arabidopsis thaliana	Q8LFN9	86.9%	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
MIR6726	ncRNA	102465434
SNORD167	snoRNA	109623456
UBE2J2	protein-coding	118424
C1QTNF12	protein-coding	388581
SCNN1D	protein-coding	6339
LINC01786	ncRNA	101928895
PUSL1	protein-coding	126789
INTS11	protein-coding	54973
DVL1	protein-coding	1855
CPTP	protein-coding	80772
TAS1R3	protein-coding	83756
MIR6727	ncRNA	102465435
B3GALT6	protein-coding	126792

Protein

Protein identifiers

Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 3 — Q96P50 (reviewed: Q96P50)

Alternative names: Centaurin-beta-5

All UniProt accessions (2): F8W850, Q96P50

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein for the ADP ribosylation factor family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96P50-3	1	yes
Q96P50-1	2
Q96P50-4	3

RefSeq proteins (1): NP_085152* (*=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
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO_Zfn_sf	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR042695	ACAP3_BAR	Domain
IPR045258	ACAP1/2/3-like	Family

Pfam: PF00169, PF01412, PF12796, PF16746

UniProt features (15 total): splice variant 3, repeat 3, domain 2, compositionally biased region 2, region of interest 2, chain 1, sequence conflict 1, zinc finger region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96P50-F1	76.31	0.52

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; golgi apparatus

Antibody reliability (HPA): IH approved · IF approved

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: 115 (showing top): GOBP_NEUROGENESIS, USF_C, NFKB_C, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, TGACATY_UNKNOWN, GOBP_NEURON_MIGRATION, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, RYTTCCTG_ETS2_B, GOCC_NEURON_PROJECTION, KEGG_ENDOCYTOSIS, GOBP_CELL_PROJECTION_ORGANIZATION, MARIADASON_REGULATED_BY_HISTONE_ACETYLATION_UP, USF2_Q6, GOCC_AXON, MYC_Q2

GO Biological Process (3): neuron migration (GO:0001764), regulation of neuron projection development (GO:0010975), actin cytoskeleton organization (GO:0030036)

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): cytoplasm (GO:0005737), growth cone (GO:0030426), plasma membrane (GO:0005886), endosome membrane (GO:0010008)

GO top-level categories

21 GO namespaces:

Category	Terms
cell migration	1
generation of neurons	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
cytoskeleton organization	1
actin filament-based process	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
site of polarized growth	1
distal axon	1
membrane	1
cell periphery	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

showing 15 of 550 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACAP3	PUSL1	Q8N0Z8	617
ACAP3	INTS11	Q5TA45	578
ACAP3	SCNN1D	P51172	530
ACAP3	MXRA8	Q9BRK3	515
ACAP3	UBE2J2	Q8N2K1	491
ACAP3	AGFG2	O95081	476
ACAP3	PRSS36	Q5K4E3	370
ACAP3	FURIN	P09958	370
ACAP3	PCSK4	Q6UW60	362
ACAP3	C1QTNF12	Q5T7M4	343
ACAP3	FITM2	Q8N6M3	337
ACAP3	NEMF	O60524	330
ACAP3	ANKRD46	Q86W74	328
ACAP3	C19orf47	Q8N9M1	310
ACAP3	ZNF410	Q86VK4	296

IntAct

Human interaction partners of ACAP3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
ACAP2	physical association	0.640	3
TAB1	physical association	0.370	1
SEPTIN6	association	0.350	1
ITGB3BP	physical association	0.000	1
SLC35G2	physical association	0.000	1

BioGRID (24 interactions; top human partners by supporting records): ACAP2 (Affinity Capture-MS; 4 records), DDX58 (Affinity Capture-RNA), EIF6 (Two-hybrid), FBXW11 (Affinity Capture-MS), HIF1AN (Affinity Capture-MS), NUDT21 (Affinity Capture-RNA), PARP4 (Proximity Label-MS), RBM25 (Affinity Capture-MS), SEPT10 (Affinity Capture-MS), SEPT11 (Affinity Capture-MS), SEPT2 (Affinity Capture-MS), SEPT3 (Affinity Capture-MS), SEPT5 (Affinity Capture-MS), SEPT6 (Affinity Capture-MS), SEPT7 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ACAP3: 277 ClinVar records (83 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	79
Likely pathogenic	4
Uncertain significance	148
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 83 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
160923	GRCh38/hg38 1p36.33-36.32(chr1:844347-2627474)x1	Pathogenic	criteria provided, multiple submitters, no conflicts	2
57049	GRCh38/hg38 1p36.33-36.31(chr1:844347-5682587)x1	Pathogenic	criteria provided, single submitter	1
57052	GRCh38/hg38 1p36.33-36.32(chr1:844347-3319395)x1	Pathogenic	criteria provided, single submitter	1
57201	GRCh38/hg38 1p36.33-36.32(chr1:844347-3006252)x1	Pathogenic	criteria provided, single submitter	1
57218	GRCh38/hg38 1p36.33-36.32(chr1:844347-3712147)x1	Pathogenic	criteria provided, single submitter	1
58037	GRCh38/hg38 1p36.33-36.32(chr1:826553-4719105)x3	Pathogenic	criteria provided, single submitter	1
58242	GRCh38/hg38 1p36.33-36.23(chr1:629025-8537745)x1	Pathogenic	criteria provided, single submitter	1
58243	GRCh38/hg38 1p36.33-36.32(chr1:629044-3346226)x1	Pathogenic	criteria provided, single submitter	1
58244	GRCh38/hg38 1p36.33-36.31(chr1:629044-7008678)x1	Pathogenic	criteria provided, single submitter	1
58289	GRCh38/hg38 1p36.33-36.32(chr1:844347-4665295)x1	Pathogenic	criteria provided, single submitter	1
58292	GRCh38/hg38 1p36.33(chr1:844347-2131805)x1	Pathogenic	criteria provided, single submitter	1
58294	GRCh38/hg38 1p36.33-36.23(chr1:859215-8747647)x1	Pathogenic	criteria provided, single submitter	1
58311	GRCh38/hg38 1p36.33-36.32(chr1:870177-4426613)x1	Pathogenic	criteria provided, single submitter	1
58313	GRCh38/hg38 1p36.33-36.32(chr1:872305-3054463)x1	Pathogenic	criteria provided, single submitter	1
58314	GRCh38/hg38 1p36.33-36.32(chr1:872305-4133409)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ACAP3’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; 35 predictions of 2,137):

Position(s)	Effect	Δscore	Sites
1:1295445	donor_loss	1.0000	2
1:1295939–1295940	acceptor_loss	1.0000	6
1:1296210	donor_loss	1.0000	2
1:1296281–1296282	acceptor_loss	1.0000	5
1:1296424	donor_loss	1.0000	2
1:1298565–1298566	donor_loss	1.0000	6
1:1298680	acceptor_loss	1.0000
1:1300507–1300508	donor_loss	1.0000	5
1:1303291	acceptor_gain	1.0000
1:1307767–1307768	donor_loss	1.0000	5

AlphaMissense

2,496 missense substitutions predicted likely pathogenic (of 5,472 scored), across 578 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
M271	9	0.868	0.970
D461	8	0.998	1.000
F332	8	0.996	1.000
H445	8	0.996	1.000
D783	8	0.996	0.999
F291	8	0.995	1.000
D11	8	0.992	0.999
F283	8	0.992	0.999
D420	8	0.989	0.997
D314	8	0.983	0.998
F582	8	0.980	0.997
D733	8	0.980	0.994
N415	8	0.979	0.999
F15	8	0.977	0.998
F591	8	0.973	0.995
F57	8	0.967	0.998
D170	8	0.966	0.990
H240	8	0.965	0.993
F755	8	0.960	0.999
N476	8	0.957	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	4.82e-06
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000792
Glioblastoma Multiforme (validation)	favorable	0.00096
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000983
Thyroid Carcinoma (TCGA)	unfavorable	0.000993

Disease associations

OMIM: gene `` | disease phenotypes: MIM:607872

GenCC curated gene-disease

Mondo (2): chromosome 1p36 deletion syndrome (MONDO:0011929), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): 1p36 deletion syndrome (Orphanet:1606)

GWAS associations

2 associations:

Study	Trait	p-value
GCST004131_103	Inflammatory bowel disease	2e-7
GCST004133_8	Ulcerative colitis	3e-6

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C535362	Chromosome 1p36 Deletion Syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
beta-lapachone	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Aspirin	increases expression	1
Catechin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	decreases expression, increases methylation	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F5AJ	EDITGENE ACAP3 Knockout Hela Cell Line	Cancer cell line	Female

Clinical trials (associated diseases)

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

showing 60 of 214 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02381457	Not specified	COMPLETED	SNP-based Microdeletion and Aneuploidy RegisTry (SMART)
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT03440697	Not specified	ACTIVE_NOT_RECRUITING	Pathogenetic Basis of Aortopathy and Aortic Valve Disease
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03577756	Not specified	COMPLETED	Neurodevelopmental Assessment of Infants With Cystic Fibrosis
NCT03654248	Not specified	COMPLETED	Let’s Get Organized in Adult Psychiatric/habilitation Care
NCT03659279	Not specified	COMPLETED	Let’s Get Organized Feasibility Study
NCT03722615	Not specified	COMPLETED	Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
NCT03770832	Not specified	ACTIVE_NOT_RECRUITING	Wearable Sensors and Video Recordings to Monitor Motor Development
NCT03830879	Not specified	RECRUITING	Shenzhen Birth Cohort Study
NCT03835689	Not specified	COMPLETED	Strongest FamiliesTM Neurodevelopmental
NCT03882788	Not specified	COMPLETED	The Effect of Anesthesia on Neurodevelopmental Outcome (NDO)
NCT03922087	Not specified	COMPLETED	No-worry Baby Project
NCT03977259	Not specified	ACTIVE_NOT_RECRUITING	Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development
NCT04043572	Not specified	UNKNOWN	The Biomarkers of Neurological Disease in Utero Study
NCT04096430	Not specified	RECRUITING	Evaluation of Effectiveness of Child-oriented Goal-setting in Paediatric Rehabilitation (the ENGAGE Approach)