ACBD3

Summary

ACBD3 (acyl-CoA binding domain containing 3, HGNC:15453) is a protein-coding gene on chromosome 1q42.12, encoding Golgi resident protein GCP60 (Q9H3P7). Involved in the maintenance of Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and Golgi.

The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is involved in the maintenance of Golgi structure and function through its interaction with the integral membrane protein giantin. It may also be involved in the hormonal regulation of steroid formation.

Source: NCBI Gene 64746 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 82 total — 4 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_022735

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15453
Approved symbol	ACBD3
Name	acyl-CoA binding domain containing 3
Location	1q42.12
Locus type	gene with protein product
Status	Approved
Aliases	GCP60, PAP7
Ensembl gene	ENSG00000182827
Ensembl biotype	protein_coding
OMIM	606809
Entrez	64746

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000366812, ENST00000464927, ENST00000912077, ENST00000912078, ENST00000912079, ENST00000959691, ENST00000959692

RefSeq mRNA: 1 — MANE Select: NM_022735 NM_022735

CCDS: CCDS1551

Canonical transcript exons

ENST00000366812 — 8 exons

Exon	Start	End
ENSE00001298070	226161531	226161689
ENSE00001305005	226154647	226154833
ENSE00001317373	226164789	226164929
ENSE00001320821	226165859	226166000
ENSE00001322552	226152335	226152619
ENSE00001324185	226159184	226159358
ENSE00001442667	226144679	226146821
ENSE00001442668	226186390	226186741

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.2151 / max 913.1803, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17746	66.2151	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	98.16	gold quality
buccal mucosa cell	CL:0002336	98.00	gold quality
choroid plexus epithelium	UBERON:0003911	97.82	gold quality
esophagus squamous epithelium	UBERON:0006920	97.69	gold quality
amniotic fluid	UBERON:0000173	97.61	gold quality
gingival epithelium	UBERON:0001949	97.25	gold quality
endothelial cell	CL:0000115	97.14	gold quality
palpebral conjunctiva	UBERON:0001812	97.02	gold quality
secondary oocyte	CL:0000655	96.93	gold quality
squamous epithelium	UBERON:0006914	96.91	gold quality
gingiva	UBERON:0001828	96.88	gold quality
tongue squamous epithelium	UBERON:0006919	96.88	gold quality
oocyte	CL:0000023	96.76	gold quality
epithelium of esophagus	UBERON:0001976	96.73	gold quality
cartilage tissue	UBERON:0002418	96.73	gold quality
germinal epithelium of ovary	UBERON:0001304	96.40	gold quality
visceral pleura	UBERON:0002401	96.24	gold quality
pleura	UBERON:0000977	95.76	gold quality
parietal pleura	UBERON:0002400	95.76	gold quality
oral cavity	UBERON:0000167	95.68	gold quality
pharyngeal mucosa	UBERON:0000355	95.58	gold quality
oviduct epithelium	UBERON:0004804	95.52	gold quality
calcaneal tendon	UBERON:0003701	95.33	gold quality
pancreatic ductal cell	CL:0002079	95.28	gold quality
corpus epididymis	UBERON:0004359	94.93	gold quality
epithelium of nasopharynx	UBERON:0001951	94.85	gold quality
cauda epididymis	UBERON:0004360	94.75	gold quality
skin of hip	UBERON:0001554	94.61	gold quality
sural nerve	UBERON:0015488	94.61	gold quality
islet of Langerhans	UBERON:0000006	94.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TBC1D22A

miRNA regulators (miRDB)

182 targeting ACBD3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
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-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 32)

• Molecular cloning, chromosomal localization and expression pattern of PAP7. (PMID:12692076)
• GCP60 interacts preferentially with one of the golgin-160 caspase cleavage fragments (residues 140-311). This strong interaction prevented the golgin-160 fragment from accumulating in the nucleus when this fragment and GCP60 were overexpressed. (PMID:16870622)
• nuclear translocation of golgin-160-(140-311) is a highly coordinated event regulated not only by cleavage of the golgin-160 head but also by the oxidation state of GCP60 (PMID:17711851)
• results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication (PMID:22124328)
• The 3A protein of picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIbeta. (PMID:22258260)
• The data were consistent with PAP7 interacting with DMT1 and regulating DMT1 expression in K562 cells by modulating expression of DMT1 protein. (PMID:22383495)
• identified ACBD3 as an interacting partner of PPM1L, and showed that this association, which recruits PPM1L to ER-Golgi membrane contact sites, is mediated by a GOLD (Golgi dynamics) domain in ACBD3 (PMID:22796112)
• ACBD3 plays an essential role in maintaining lipid homeostasis via regulating SREBP1’s processing pathway and thus impacting cellular lipogenesis. (PMID:23166793)
• Using affinity purification-mass spectrometry, we identified the putative Rab33 GTPase-activating proteins TBC1D22A and TBC1D22B as ACBD3-interacting factors. (PMID:23572552)
• Authors found that the Golgi protein acyl-coenzyme A binding domain-containing 3 (ACBD3), interacts with the 3A proteins of poliovaccine Sabintpe 2 and coxsackievirus A17 at viral RNA replication sites. (PMID:23926333)
• ACBD3 mediates mHtt cytotoxicity via a Rhes/mHtt/ACBD3 complex. (PMID:24012756)
• Host ACBD3, PI4KIIIBETA and Aichi virus proteins complexes enhances phosphatidylinositol 4-phosphate synthesis and is critical for viral replication. (PMID:24672044)
• Authors found that NS5A and PI4KB competed for association of acyl-coenzyme A binding domain containing protein 3 (ACBD3), which inhibited hepatitis C virus replication. (PMID:24792752)
• these findings suggest that ACBD3 has prominent impacts on cellular NAD(+) metabolism via regulating PARP1 activation-dependent auto-modification and thus cell metabolism and function. (PMID:25940138)
• ACBD3 was found as a gene expression variability marker in 8-cell human embryos. (PMID:26288249)
• The authors propose a model in which interaction between Salmonella enterica serovar Typhimurium SseF and SseG enables both proteins to bind ACBD3, thereby anchoring Salmonella-containing vacuoles at the Golgi network and facilitating bacterial replication. (PMID:27406559)
• Results show that Aichi virus 3A protein activates the lipid kinase activity of PI4KIIIb,which activation is sensitized by the protein ACBD3. The interfaces between PI4KIIIbeta-ACBD3 and ACBD3-3A were mapped with hydrogen-deuterium exchange mass spectrometry. (PMID:27989622)
• Kobuviral non-structural 3A proteins act as molecular harnesses to hijack the host ACBD3 protein. (PMID:28065508)
• These results reveal a mechanism of EV71 replication that involves host ACBD3 for viral replication. (PMID:28303920)
• that ACBD3 may represent candidate therapeutic targets to enable the elimination of breast cancer stem cells (PMID:29307786)
• the component proteins of the machinery, OSBP, VAP, SAC1, and PITPNB, are all essential host factors for AiV replication. Importantly, the machinery is directly recruited to the RNA replication sites through previously unknown interactions of VAP/OSBP/SAC1 with the AiV proteins and with ACBD3. (PMID:29367253)
• In vitro reconstitution revealed that the membrane is necessary for the formation of ACBD3:PI4KB:Rab11 protein complex at physiological (nanomolar) concentrations. (PMID:30679637)
• Altogether, these data provide new insight into the central role of ACBD3 in recruiting PI4KB by enterovirus 3A and reveal the minimal domains of ACBD3 involved in recruiting PI4KB and supporting enterovirus replication. (PMID:30755512)
• This review aims to give a timely overview of recent findings on Acyl-CoA-binding domain-containing 3 protein, including its emerging role in membrane domain organization at the Golgi and the mitochondria. [review] (PMID:31022988)
• The picornaviruses use their small nonstructural protein 3A that binds the Golgi dynamics domain of the ACBD3 protein. (PMID:31583778)
• Knock-Out of ACBD3 Leads to Dispersed Golgi Structure, but Unaffected Mitochondrial Functions in HEK293 and HeLa Cells. (PMID:34298889)
• ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner. (PMID:34332983)
• ACBD3 Bioinformatic Analysis and Protein Expression in Breast Cancer Cells. (PMID:36012147)
• An A-kinase anchoring protein (ACBD3) coordinates traffic-induced PKA activation at the Golgi. (PMID:37044218)
• The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi. (PMID:37195633)
• Identification of ACBD3 as a new molecular biomarker in pan-cancers through bioinformatic analysis: a preclinical study. (PMID:38098097)
• Recruitment of PI4KIIIbeta to the Golgi by ACBD3 is dependent on an upstream pathway of a SNARE complex and golgins. (PMID:38134218)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ACBD3	ENSDARG00000024602
danio_rerio	acbd3	ENSDARG00000042623
mus_musculus	Acbd3	ENSMUSG00000026499
drosophila_melanogaster	CG14232	FBGN0031061
caenorhabditis_elegans		WBGENE00012765

Paralogs (1): TMED8 (ENSG00000100580)

Protein

Protein identifiers

Golgi resident protein GCP60 — Q9H3P7 (reviewed: Q9H3P7)

Alternative names: Acyl-CoA-binding domain-containing protein 3, Golgi complex-associated protein 1, Golgi phosphoprotein 1, PBR- and PKA-associated protein 7, Peripheral benzodiazepine receptor-associated protein PAP7

All UniProt accessions (1): Q9H3P7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the maintenance of Golgi structure by interacting with giantin, affecting protein transport between the endoplasmic reticulum and Golgi. Involved in hormone-induced steroid biosynthesis in testicular Leydig cells. Recruits PI4KB to the Golgi apparatus membrane; enhances the enzyme activity of PI4KB activity via its membrane recruitment thereby increasing the local concentration of the substrate in the vicinity of the kinase. (Microbial infection) Plays an essential role in Aichi virus RNA replication by recruiting PI4KB at the viral replication sites.

Subunit / interactions. Homodimer. Interacts with the C-terminal cytoplasmic domain of giantin/GOLGB1. Interacts with PBR and PKA regulatory subunit RI-alpha. Does not interact with PKA regulatory subunit RI-beta nor PKA regulatory subunit RII-alpha. Interacts (via Q domain) with PI4KB (via N-terminus). Interacts (via Q domain) with TBC1D22A and TBC1D22B; interactions with PI4KB and with TBC1D22A and TBC1D22B are mutually exclusive. Interacts with C10ORF76 and RAB11B. (Microbial infection) Interacts (via GOLD domain) with 3A proteins from various picornaviruses, including poliovirus, enterovirus A71, enterovirus D68, hepatitis A virus, human parechovirus 1, poliovirus, Human rhinovirus-14 (Hrv-14), coysackievirus B2, coysackievirus B3, coysackievirus B5, Aichi virus and human klassevirus. Interacts (via GOLD domain) with Aichi virus protein 3A; this interaction allows the formation of a 3A/ACBD3/PI4KB complex in order to synthesize PI4P at the viral RNA replication sites. Interacts with Aichi virus protein 2B. Interacts with Aichi virus protein 2C.

Subcellular location. Golgi apparatus membrane. Mitochondrion.

Tissue specificity. Ubiquitous, with highest expression in testis and ovary.

Domain organisation. The central Gln-rich region (Q domain) is involved in binding to PI4KB, TBC1D22A and TBC1D22B. The C-terminal GOLD domain is essential for giantin binding. The GOLD domain is also involved in homodimerization. (Microbial infection) The GOLD domain is involved in binding to the picornaviral protein 3A.

RefSeq proteins (1): NP_073572* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000582	Acyl-CoA-binding_protein	Domain
IPR009038	GOLD_dom	Domain
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR022408	Acyl-CoA-binding_prot_CS	Conserved_site
IPR035984	Acyl-CoA-binding_sf	Homologous_superfamily
IPR036598	GOLD_dom_sf	Homologous_superfamily
IPR052269	Golgi-PI4KB_interaction	Family

Pfam: PF00887, PF13897

UniProt features (85 total): mutagenesis site 39, strand 11, sequence conflict 7, region of interest 6, modified residue 6, helix 4, compositionally biased region 3, chain 2, domain 2, initiator methionine 1, coiled-coil region 1, site 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
5LZ1	X-RAY DIFFRACTION	2
6HLN	X-RAY DIFFRACTION	2.1
6HMV	X-RAY DIFFRACTION	2.24
6HM8	X-RAY DIFFRACTION	2.28
5TDQ	X-RAY DIFFRACTION	2.49
6HLV	X-RAY DIFFRACTION	2.5
5LZ6	X-RAY DIFFRACTION	2.6
6HLW	X-RAY DIFFRACTION	2.73
6HLT	X-RAY DIFFRACTION	2.81
5LZ3	X-RAY DIFFRACTION	3
2N72	SOLUTION NMR
2N73	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3P7-F1	80.50	0.64

Functional residue map

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

Catalytic / active sites (1): 399 (membrane-binding)

Post-translational modifications (6): 2, 13, 18, 20, 43, 47

Mutagenesis-validated functional residues (39):

Position	Phenotype
243	no effect on pi4kb- and tbc1d22b-binding.
244	no effect on pi4kb- and tbc1d22b-binding.
245	no effect on pi4kb- and tbc1d22b-binding.
246	partial loss of pi4kb- and tbc1d22b-binding.
253	no effect on pi4kb- and tbc1d22b-binding.
254	no effect on pi4kb- and tbc1d22b-binding.
256–258	loss of pi4kb-, tbc1d22a- and tbc1d22b-binding.
257	partial loss of pi4kb- and tbc1d22b-binding.
258–259	complete loss of interaction with pi4kb.
258–259	loss of interaction with pi4kb.
258	differential effect on pi4kb- and tbc1d22b-binding, with pi4kb-binding being much more affected than tbc1d22b-binding.
259	no effect on pi4kb- and tbc1d22b-binding.
260	no effect on pi4kb- and tbc1d22b-binding.
261	no effect on pi4kb- and tbc1d22b-binding.
264–266	no effect on pi4kb-, tbc1d22a- and tbc1d22b-binding.
266	no loss of interaction with pi4kb.
267–269	loss of pi4kb-, tbc1d22a- and tbc1d22b-binding.
275	no effect on pi4kb- and tbc1d22b-binding.
276	no effect on pi4kb- and tbc1d22b-binding.
282–285	loss of pi4kb-, tbc1d22a- and tbc1d22b-binding.
284	almost complete loss of pi4kb- and tbc1d22b-binding.
285	differential loss of pi4kb- and tbc1d22b-binding, with pi4kb-binding being much more affected than tbc1d22b-binding.
286	no effect on pi4kb- and tbc1d22b-binding.
287	no effect on pi4kb- and tbc1d22b-binding.
288	almost complete loss of pi4kb- and tbc1d22b-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis

MSigDB gene sets: 212 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, REACTOME_MEMBRANE_TRAFFICKING, TTGGGAG_MIR150, ATGTTAA_MIR302C, PATIL_LIVER_CANCER, MARTINEZ_RB1_TARGETS_UP, MODULE_239, WANG_LMO4_TARGETS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GROSS_HYPOXIA_VIA_ELK3_DN, GOBP_STEROID_BIOSYNTHETIC_PROCESS, CYTAGCAAY_UNKNOWN, GOBP_LIPID_METABOLIC_PROCESS, AACTTT_UNKNOWN, GOBP_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (2): steroid biosynthetic process (GO:0006694), lipid metabolic process (GO:0006629)

GO Molecular Function (3): fatty-acyl-CoA binding (GO:0000062), protein kinase A regulatory subunit binding (GO:0034237), protein binding (GO:0005515)

GO Cellular Component (4): Golgi membrane (GO:0000139), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
steroid metabolic process	1
lipid biosynthetic process	1
primary metabolic process	1
acyl-CoA binding	1
fatty acid derivative binding	1
protein kinase A binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACBD3	GOLGB1	Q14789	987
ACBD3	TSPO	P30536	986
ACBD3	VDAC1	P21796	955
ACBD3	PI4KB	P78405	925
ACBD3	DBI	P07108	886
ACBD3	BPNT1	O95861	851
ACBD3	EPRS1	P07814	833
ACBD3	SLC11A2	P49281	827
ACBD3	BLZF1	Q9H2G9	819
ACBD3	STAR	P49675	797
ACBD3	GOLGA3	Q08378	791
ACBD3	OSBP	P22059	750
ACBD3	ARMH3	Q5T2E6	722
ACBD3	TSPOAP1	O95153	713
ACBD3	NUMBL	Q9Y6R0	641

IntAct

206 interactions, top by confidence:

A	B	Type	Score
ACBD3	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.740
ACBD3		psi-mi:“MI:0915”(physical association)	0.740
ACBD3		psi-mi:“MI:0914”(association)	0.740
ACBD3	TBC1D22B	psi-mi:“MI:0914”(association)	0.740
	ACBD3	psi-mi:“MI:0915”(physical association)	0.740
	ACBD3	psi-mi:“MI:0407”(direct interaction)	0.740
ACBD3	TBC1D22A	psi-mi:“MI:0915”(physical association)	0.720
TBC1D22A	ACBD3	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ACBD3		psi-mi:“MI:0915”(physical association)	0.590
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
	ACBD3	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (354): ACBD3 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), ACBD3 (Co-fractionation), ACBD3 (Co-fractionation), ACBD3 (Co-fractionation), ACBD3 (Affinity Capture-MS), ACBD3 (Proximity Label-MS), ACBD3 (Proximity Label-MS), ACBD3 (Proximity Label-MS), ACBD3 (Proximity Label-MS), ACBD3 (Two-hybrid), ACBD3 (Proximity Label-MS), ACBD3 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS)

ESM2 similar proteins: A6QR44, O15169, O35144, O35589, O35625, O54828, O88974, P49140, P53349, Q02225, Q08BR4, Q12789, Q13233, Q13506, Q15047, Q15554, Q1LZ89, Q2V2M9, Q3MHI4, Q3ULM0, Q3UWM4, Q53F19, Q5HYC2, Q5RGA4, Q5XJV7, Q61122, Q62315, Q62722, Q62925, Q63068, Q6INA9, Q6P1H6, Q6ZMT4, Q7TP65, Q80TJ7, Q86XL3, Q8BZR9, Q8K284, Q8WVT3, Q8WYQ5

Diamond homologs: A0FKI7, A2VDR2, A5WV69, O01805, O04066, O09035, O22643, O75521, P07106, P07107, P07108, P11030, P12026, P31786, P31787, P42281, P45882, P45883, P56702, P57752, P61867, P61868, P82934, Q20507, Q2KHT9, Q39315, Q39779, Q3SZF0, Q4V869, Q4V8X4, Q502L1, Q54GC8, Q5FXM5, Q5R7P6, Q5R7V3, Q5RJK8, Q5T8D3, Q5VRM0, Q5XG73, Q5XIC0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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
EPHA-mediated growth cone collapse	6	18.3×	1e-04
EPH-ephrin mediated repulsion of cells	8	14.1×	3e-05
PI3K Cascade	5	10.9×	6e-03
NCAM signaling for neurite out-growth	5	10.9×	6e-03
Transport of vitamins, nucleosides, and related molecules	5	10.9×	6e-03
EPH-Ephrin signaling	8	10.6×	1e-04
Constitutive Signaling by Aberrant PI3K in Cancer	10	10.2×	3e-05
SLC transporter disorders	6	9.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	9	26.5×	3e-08
regulation of ERK1 and ERK2 cascade	5	20.3×	5e-04
ephrin receptor signaling pathway	8	19.2×	2e-06
cell surface receptor protein tyrosine kinase signaling pathway	15	18.2×	5e-12
protein autophosphorylation	9	9.1×	1e-04
positive regulation of neuron projection development	9	8.6×	1e-04
positive regulation of MAPK cascade	15	8.5×	1e-07
axon guidance	13	8.2×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	68
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1527559	GRCh37/hg19 1q41-42.13(chr1:221303919-227461343)	Pathogenic
253654	GRCh37/hg19 1q31.3-42.13(chr1:197811907-228997888)x3	Pathogenic
3148877	GRCh37/hg19 1q41-42.12(chr1:216147522-226765691)x1	Pathogenic
814166	GRCh37/hg19 1q41-42.13(chr1:222641389-228137574)x1	Pathogenic

SpliceAI

1677 predictions. Top by Δscore:

Variant	Effect	Δscore
1:226146817:GTTTT:G	acceptor_gain	1.0000
1:226146818:TTTT:T	acceptor_gain	1.0000
1:226146819:TTT:T	acceptor_gain	1.0000
1:226146820:TT:T	acceptor_gain	1.0000
1:226146822:C:CC	acceptor_gain	1.0000
1:226146822:CTGTA:C	acceptor_loss	1.0000
1:226146831:C:CT	acceptor_gain	1.0000
1:226152340:T:TA	donor_gain	1.0000
1:226154642:CCTA:C	donor_loss	1.0000
1:226154643:CTA:C	donor_loss	1.0000
1:226154644:TACCT:T	donor_loss	1.0000
1:226154645:A:AC	donor_gain	1.0000
1:226154645:A:AT	donor_loss	1.0000
1:226154645:AC:A	donor_gain	1.0000
1:226154646:C:CC	donor_gain	1.0000
1:226154646:CC:C	donor_gain	1.0000
1:226154830:CTGC:C	acceptor_gain	1.0000
1:226154832:GCCT:G	acceptor_loss	1.0000
1:226154834:C:T	acceptor_loss	1.0000
1:226154835:T:G	acceptor_loss	1.0000
1:226156710:T:TA	donor_gain	1.0000
1:226159178:TCGTA:T	donor_loss	1.0000
1:226159179:CGTA:C	donor_loss	1.0000
1:226159180:GTAC:G	donor_loss	1.0000
1:226159181:TA:T	donor_loss	1.0000
1:226159357:GCCTA:G	acceptor_loss	1.0000
1:226159359:C:CA	acceptor_loss	1.0000
1:226161526:CTTA:C	donor_gain	1.0000
1:226161527:TTAC:T	donor_loss	1.0000
1:226161528:TA:T	donor_loss	1.0000

AlphaMissense

3435 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:226146633:A:C	Y522D	1.000
1:226146638:A:T	V520D	1.000
1:226146643:T:A	K518N	1.000
1:226146643:T:G	K518N	1.000
1:226146644:T:A	K518I	1.000
1:226146667:G:C	N510K	1.000
1:226146667:G:T	N510K	1.000
1:226146674:A:G	F508S	1.000
1:226146680:A:G	L506P	1.000
1:226146683:A:G	L505P	1.000
1:226146692:C:T	G502E	1.000
1:226146705:A:C	Y498D	1.000
1:226146711:G:C	H496D	1.000
1:226146716:C:T	G494D	1.000
1:226146717:C:G	G494R	1.000
1:226146719:G:T	A493D	1.000
1:226146743:C:G	R485P	1.000
1:226152421:C:T	G430E	1.000
1:226152422:C:A	G430W	1.000
1:226152423:A:C	F429L	1.000
1:226152423:A:T	F429L	1.000
1:226152425:A:G	F429L	1.000
1:226152433:T:A	D426V	1.000
1:226152448:G:T	A421D	1.000
1:226152449:C:G	A421P	1.000
1:226152450:A:C	F420L	1.000
1:226152450:A:T	F420L	1.000
1:226152451:A:G	F420S	1.000
1:226152452:A:G	F420L	1.000
1:226152456:C:A	W418C	1.000

dbSNP variants (sampled 300 via entrez): RS1000004133 (1:226176250 G>A), RS1000095051 (1:226156343 A>G), RS1000098866 (1:226175959 T>C), RS1000177280 (1:226162795 C>T), RS1000192656 (1:226159518 T>A,C,G), RS1000247944 (1:226169198 A>T), RS1000347591 (1:226156985 A>G), RS1000355070 (1:226178664 A>C), RS1000369393 (1:226181829 A>G), RS1000401037 (1:226163097 G>A), RS1000513210 (1:226164119 A>G,T), RS1000531033 (1:226178949 T>G), RS1000668232 (1:226167260 T>C), RS1000799627 (1:226157939 G>A), RS1000804902 (1:226166945 T>C)

Disease associations

OMIM: gene MIM:606809 | disease phenotypes: MIM:602966

GenCC curated gene-disease

Mondo (1): orofacial cleft 2 (MONDO:0011276)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003473_31	Aggressiveness in attention deficit hyperactivity disorder	7.000000e-06
GCST009391_205	Metabolite levels	9.000000e-06
GCST010396_214	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010488	glycerol-3-phosphate measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566419	Orofacial Cleft 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067245 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.38	Kd	41.55	nM	CHEMBL5653589
7.38	ED50	41.55	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147782: Binding affinity to human ACBD3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0415	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
tetrahydropalmatine	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
pentabromodiphenyl ether	increases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650824	Binding	Binding affinity to human ACBD3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SB16	HAP1 ACBD3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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