ACIN1

Summary

ACIN1 (apoptotic chromatin condensation inducer 1, HGNC:17066) is a protein-coding gene on chromosome 14q11.2, encoding Apoptotic chromatin condensation inducer in the nucleus (Q9UKV3). Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. It is a selective cancer dependency (DepMap: 84.4% of cell lines).

Apoptosis is defined by several morphologic nuclear changes, including chromatin condensation and nuclear fragmentation. This gene encodes a nuclear protein that induces apoptotic chromatin condensation after activation by caspase-3, without inducing DNA fragmentation. This protein has also been shown to be a component of a splicing-dependent multiprotein exon junction complex (EJC) that is deposited at splice junctions on mRNAs, as a consequence of pre-mRNA splicing. It may thus be involved in mRNA metabolism associated with splicing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 22985 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 200 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 84.4% of screened cell lines
• MANE Select transcript: NM_001386863

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17066
Approved symbol	ACIN1
Name	apoptotic chromatin condensation inducer 1
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0670, fSAP152
Ensembl gene	ENSG00000100813
Ensembl biotype	protein_coding
OMIM	604562
Entrez	22985

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 25 protein_coding, 10 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000262710, ENST00000338631, ENST00000357481, ENST00000397341, ENST00000457657, ENST00000473758, ENST00000553501, ENST00000553721, ENST00000553790, ENST00000554680, ENST00000554708, ENST00000554979, ENST00000555053, ENST00000555352, ENST00000555395, ENST00000555478, ENST00000555566, ENST00000555807, ENST00000556052, ENST00000557039, ENST00000557432, ENST00000557515, ENST00000605057, ENST00000897552, ENST00000897553, ENST00000897554, ENST00000897555, ENST00000897556, ENST00000897557, ENST00000897558, ENST00000897559, ENST00000897560, ENST00000897561, ENST00000897562, ENST00000916201, ENST00000916202, ENST00000916203, ENST00000916204, ENST00000941951

RefSeq mRNA: 6 — MANE Select: NM_001386863 NM_001164814, NM_001164815, NM_001164816, NM_001164817, NM_001386863, NM_014977

CCDS: CCDS53887, CCDS53888, CCDS53889, CCDS55905, CCDS91850, CCDS9587

Canonical transcript exons

ENST00000605057 — 19 exons

Exon	Start	End
ENSE00000653853	23079547	23080809
ENSE00000653856	23089982	23090101
ENSE00000653863	23090522	23090633
ENSE00000653870	23093479	23093544
ENSE00000889201	23081748	23081836
ENSE00002463385	23058564	23059474
ENSE00003503403	23063436	23063577
ENSE00003512587	23062168	23062275
ENSE00003515758	23078820	23079038
ENSE00003524252	23065966	23066008
ENSE00003525916	23062929	23063074
ENSE00003558997	23069476	23069617
ENSE00003582614	23061298	23061622
ENSE00003594887	23094975	23095136
ENSE00003643304	23062416	23062523
ENSE00003668369	23064105	23064257
ENSE00003671194	23064355	23064488
ENSE00003673940	23061084	23061184
ENSE00003715910	23078151	23078266

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.3502 / max 1096.3428, expressed in 1828 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142308	78.8544	1827
142302	36.9354	1818
142299	0.6027	317
142303	0.4190	206
142301	0.1770	74
142300	0.1309	53
142305	0.0985	28
142306	0.0911	29
142307	0.0250	4
142304	0.0161	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.06	gold quality
right lobe of thyroid gland	UBERON:0001119	98.90	gold quality
sural nerve	UBERON:0015488	98.75	gold quality
left lobe of thyroid gland	UBERON:0001120	98.71	gold quality
right ovary	UBERON:0002118	98.65	gold quality
left ovary	UBERON:0002119	98.57	gold quality
body of uterus	UBERON:0009853	98.56	gold quality
endocervix	UBERON:0000458	98.55	gold quality
metanephros cortex	UBERON:0010533	98.48	gold quality
right adrenal gland cortex	UBERON:0035827	98.46	gold quality
right adrenal gland	UBERON:0001233	98.44	gold quality
adenohypophysis	UBERON:0002196	98.39	gold quality
lower esophagus mucosa	UBERON:0035834	98.38	gold quality
granulocyte	CL:0000094	98.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.35	gold quality
ganglionic eminence	UBERON:0004023	98.35	gold quality
ventricular zone	UBERON:0003053	98.22	gold quality
mucosa of stomach	UBERON:0001199	98.21	gold quality
left uterine tube	UBERON:0001303	98.19	gold quality
ectocervix	UBERON:0012249	98.18	gold quality
stromal cell of endometrium	CL:0002255	98.17	gold quality
left adrenal gland	UBERON:0001234	98.15	gold quality
left adrenal gland cortex	UBERON:0035825	98.15	gold quality
gall bladder	UBERON:0002110	98.12	gold quality
body of pancreas	UBERON:0001150	98.11	gold quality
minor salivary gland	UBERON:0001830	98.09	gold quality
body of stomach	UBERON:0001161	98.03	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.01	gold quality
transverse colon	UBERON:0001157	97.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.04
E-CURD-112	no	2.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting ACIN1, 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-4455	100.00	65.48	1587
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 84.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 16)

• Akt phosphorylation of acinus on serine 422 and 573 results in its resistance to caspase cleavage in the nucleus and the inhibition of acinus-dependent chromatin condensation. (PMID:16177823)
• Acinus is not involved in DNA condensation but rather has a role in internucleosomal DNA cleavage during programmed cell death (PMID:16537548)
• We found hypermethylation of the ACIN1 gene in early stage lung adenocarcinoma. The role of methylation status in the development and malignant transformation of lung adenocarcinoma requires clarification. (PMID:17409846)
• identify Acinus-S’ as a novel RAR-interacting protein[Acinus-S’] (PMID:18250153)
• The authors report here that AAC-11, a survival protein whose expression prevents apoptosis that occurs on deprivation of growth factors, physiologically binds to Acinus and prevents Acinus-mediated DNA fragmentation. (PMID:19387494)
• A critical role for AKT activation in protecting cells from ionizing radiation-induced apoptosis and the regulation of acinus gene expression is reported. (PMID:19615784)
• Study shows that transcription corepressor CtBP2 directly binds acinus, which is regulated by nerve growth factor (NGF), inhibiting its stimulatory effect on cyclin A1, but not cyclin A2, expression in leukemia. (PMID:19668232)
• Chronic low-dose radiation increases the levels of AKT and acinus proteins via NF-kappaB activation (PMID:23205493)
• An electronegative region on acinusS restricts SRPK2 phosphorylation to a single specific site. (PMID:24444330)
• Differences in the nuclear localization of Acinus-S’ and Acinus-L may suggest that these two isoforms have different functional roles. (PMID:25079509)
• the ligand-dependent splicing activity of Acinus is related to the retinoic acid-activated retinoic acid receptor (PMID:25205379)
• acinus L was identified as a potential novel mTORC1 target. (PMID:25907765)
• Genome-wide identification of RNA targets of Acinus revealed its role in splicing regulation as well as its involvement in other cellular pathways, including cell cycle progression. (PMID:27365209)
• We conclude that RNPS1 is a key factor for the quality control of mRNAs that is essential for the phenotypes including cell division. (PMID:29366779)
• ACIN1 mRNA was highly expressed in platelets of lung cancer patients (PMID:30201066)
• The SRSF3-MBNL1-Acin1 circuit constitutes an emerging axis to lessen DNA fragmentation in colorectal cancer via an alternative splicing mechanism. (PMID:33142236)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	acin1b	ENSDARG00000026842
danio_rerio	acin1a	ENSDARG00000054290
mus_musculus	Acin1	ENSMUSG00000022185
rattus_norvegicus	Acin1	ENSRNOG00000013533
drosophila_melanogaster	Acn	FBGN0263198
caenorhabditis_elegans	acin-1	WBGENE00016601

Protein

Protein identifiers

Apoptotic chromatin condensation inducer in the nucleus — Q9UKV3 (reviewed: Q9UKV3)

All UniProt accessions (7): Q9UKV3, A0A087WYN3, A0A087X0D2, E7EQT4, G3V3B0, G3V3T3, S4R3H4

UniProt curated annotations — full annotation on UniProt →

Function. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells.

Subunit / interactions. Found in a mRNA splicing-dependent exon junction complex (EJC). Component of the heterotrimeric ASAP (apoptosis- and splicing-associated protein) complexes consisting of RNPS1, SAP18 and different isoforms of ACIN1; the association of SAP18 seems to require a preformed RNPS1:ACIN1 complex. Interacts with API5. Interacts with SRPK2 in a phosphorylation-dependent manner.

Subcellular location. Nucleus. Nucleus speckle. Nucleoplasm.

Tissue specificity. Ubiquitous. The Ser-1180 phosphorylated form (by SRPK2) is highly expressed and phosphorylated in patients with myeloid hematologic malignancies.

Post-translational modifications. Phosphorylation on Ser-1180 by SRPK2 up-regulates its stimulatory effect on cyclin A1. Undergoes proteolytic cleavage; the processed form is active, contrary to the uncleaved form.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UKV3-1	1, L	yes
Q9UKV3-2	2, S'
Q9UKV3-3	3, S
Q9UKV3-5	4

RefSeq proteins (6): NP_001158286, NP_001158287, NP_001158288, NP_001158289, NP_001373792, NP_055792 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003034	SAP_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR032552	RSB_motif	Conserved_site
IPR034257	Acinus_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR052793	EJC-associated_protein	Family

Pfam: PF02037, PF16294

UniProt features (117 total): modified residue 50, compositionally biased region 25, cross-link 11, region of interest 7, splice variant 6, sequence variant 6, helix 4, strand 3, chain 1, domain 1, mutagenesis site 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6G6S	X-RAY DIFFRACTION	1.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKV3-F1	51.21	0.06

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): 1093–1094 (cleavage; by caspase-3)

Post-translational modifications (61): 825, 132, 166, 169, 208, 210, 216, 240, 243, 254, 269, 295, 326, 328, 365, 384, 386, 388, 393, 400 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
1093	abolishes cleavage by casp3 and chromatin condensation activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-111465	Apoptotic cleavage of cellular proteins
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-109581	Apoptosis
R-HSA-5357801	Programmed Cell Death
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-75153	Apoptotic execution phase
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 209 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, RACCACAR_AML_Q6, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GGGTGGRR_PAX4_03, GOBP_CHROMOSOME_CONDENSATION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, TCF4_Q5, GOBP_REGULATION_OF_HEMOPOIESIS

GO Biological Process (8): mRNA processing (GO:0006397), RNA splicing (GO:0008380), erythrocyte differentiation (GO:0030218), apoptotic chromosome condensation (GO:0030263), positive regulation of apoptotic process (GO:0043065), positive regulation of monocyte differentiation (GO:0045657), negative regulation of mRNA splicing, via spliceosome (GO:0048025), apoptotic process (GO:0006915)

GO Molecular Function (5): nucleic acid binding (GO:0003676), RNA binding (GO:0003723), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear speck (GO:0016607), ASAP complex (GO:0061574), nucleolus (GO:0005730), nuclear lumen (GO:0031981), exon-exon junction complex (GO:0035145)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Apoptotic execution phase	1
mRNA Splicing	1
Programmed Cell Death	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1
Apoptosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
nuclear lumen	2
cellular anatomical structure	2
mRNA metabolic process	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
chromosome condensation	1
apoptotic nuclear changes	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
positive regulation of myeloid leukocyte differentiation	1
monocyte differentiation	1
regulation of monocyte differentiation	1
mRNA splicing, via spliceosome	1
negative regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
negative regulation of mRNA processing	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1
protein-containing complex	1
intracellular membraneless organelle	1
nucleus	1
intracellular organelle lumen	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

2072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACIN1	RNPS1	Q15287	992
ACIN1	SAP18	O00422	971
ACIN1	DFFB	O76075	875
ACIN1	HNRNPU	Q00839	853
ACIN1	PNN	Q9H307	817
ACIN1	MAGOHB	Q96A72	697
ACIN1	EIF4A3	P38919	694
ACIN1	MAGOH	P50606	691
ACIN1	SRRM1	Q8IYB3	670
ACIN1	DDX39B	Q13838	651
ACIN1	API5	Q9BZZ5	623
ACIN1	SRRM2	Q9UQ35	600
ACIN1	WIZ	O95785	587
ACIN1	RBM8A	Q9Y5S9	584
ACIN1	UPF3B	Q9BZI7	580

IntAct

236 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
PNN	ACIN1	psi-mi:“MI:0915”(physical association)	0.740
SARNP	DDX39A	psi-mi:“MI:0914”(association)	0.740
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
U2AF1	U2AF2	psi-mi:“MI:0914”(association)	0.670
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
LUC7L2	ZRANB2	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
SARNP	ZC3H11A	psi-mi:“MI:0914”(association)	0.610
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
INSL6	POTEF	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L2	AP3B1	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
TMEM184B	INPPL1	psi-mi:“MI:0914”(association)	0.530
DENND2D	HSPA8	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530

BioGRID (423): ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), ACIN1 (Affinity Capture-MS), RNPS1 (Co-fractionation)

ESM2 similar proteins: A0JNH1, A1A519, A4IH95, A6H7B4, A6NFA0, A6NGY1, A6NMN3, B2RQL2, D2J0Y4, F1N8V3, F1RDM5, P59598, Q05AH6, Q0P5X5, Q0VET5, Q14B48, Q1RN00, Q2YDE2, Q32LN6, Q3UXL4, Q4R7L6, Q52KN3, Q5EBJ4, Q5M831, Q5RJL0, Q5T0L3, Q64ET8, Q66H04, Q66LM5, Q66LM6, Q68A65, Q68D20, Q6DIA7, Q6GQV1, Q6NWJ0, Q6ZRS4, Q6ZVD7, Q80VY2, Q811R2, Q8BHW6

Diamond homologs: Q9JIX8, Q9UKV3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SRPK2	up-regulates	ACIN1	phosphorylation
“Caspase 3 complex”	up-regulates	ACIN1	cleavage
ACIN1	up-regulates	Chromatine_condensation
CASP3	up-regulates	ACIN1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 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
Transport of Mature Transcript to Cytoplasm	10	27.6×	9e-11
mRNA 3’-end processing	18	25.7×	4e-19
RNA Polymerase II Transcription Termination	14	22.3×	7e-14
mRNA Splicing	26	20.7×	3e-25
mRNA Polyadenylation	29	18.5×	1e-26
Transport of Mature mRNA derived from an Intron-Containing Transcript	16	17.6×	4e-14
mRNA Splicing - Major Pathway	43	17.0×	4e-39
Processing of Capped Intron-Containing Pre-mRNA	28	16.7×	1e-24

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	8	34.8×	7e-09
spliceosomal complex assembly	10	34.2×	5e-11
U2-type prespliceosome assembly	9	31.9×	1e-09
mRNA cis splicing, via spliceosome	5	28.2×	8e-05
regulation of mRNA splicing, via spliceosome	5	25.2×	1e-04
regulation of mRNA processing	5	25.2×	1e-04
RNA splicing, via transesterification reactions	7	24.8×	1e-06
alternative mRNA splicing, via spliceosome	5	19.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	170
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2968 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23059470:ACGAT:A	acceptor_gain	1.0000
14:23059471:CGAT:C	acceptor_gain	1.0000
14:23059471:CGATC:C	acceptor_gain	1.0000
14:23059472:GAT:G	acceptor_gain	1.0000
14:23059473:AT:A	acceptor_gain	1.0000
14:23059475:C:CA	acceptor_loss	1.0000
14:23059475:C:CC	acceptor_gain	1.0000
14:23059477:G:C	acceptor_gain	1.0000
14:23059481:CCAGG:C	acceptor_gain	1.0000
14:23059482:C:CT	acceptor_gain	1.0000
14:23059482:C:T	acceptor_gain	1.0000
14:23059483:A:T	acceptor_gain	1.0000
14:23059485:G:C	acceptor_gain	1.0000
14:23059485:G:GC	acceptor_gain	1.0000
14:23061080:TCAC:T	donor_loss	1.0000
14:23061081:CAC:C	donor_loss	1.0000
14:23061082:A:AC	donor_gain	1.0000
14:23061082:AC:A	donor_gain	1.0000
14:23061082:ACCTG:A	donor_loss	1.0000
14:23061083:C:CT	donor_gain	1.0000
14:23061083:CC:C	donor_gain	1.0000
14:23061083:CCT:C	donor_gain	1.0000
14:23061083:CCTG:C	donor_gain	1.0000
14:23061083:CCTGG:C	donor_gain	1.0000
14:23061180:TTTCT:T	acceptor_gain	1.0000
14:23061181:TTCT:T	acceptor_gain	1.0000
14:23061182:TCTC:T	acceptor_gain	1.0000
14:23061183:CT:C	acceptor_gain	1.0000
14:23061184:TCTGA:T	acceptor_loss	1.0000
14:23061185:C:CC	acceptor_gain	1.0000

AlphaMissense

8263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23061103:A:G	L1227P	1.000
14:23061105:C:A	W1226C	1.000
14:23061105:C:G	W1226C	1.000
14:23061107:A:G	W1226R	1.000
14:23061107:A:T	W1226R	1.000
14:23061110:A:C	Y1225D	1.000
14:23061110:A:G	Y1225H	1.000
14:23061112:A:C	I1224S	1.000
14:23061112:A:T	I1224N	1.000
14:23061118:G:T	P1222H	1.000
14:23061130:G:A	T1218I	1.000
14:23061132:C:A	K1217N	1.000
14:23061132:C:G	K1217N	1.000
14:23061138:G:C	F1215L	1.000
14:23061138:G:T	F1215L	1.000
14:23061139:A:C	F1215C	1.000
14:23061139:A:G	F1215S	1.000
14:23061140:A:C	F1215V	1.000
14:23061140:A:G	F1215L	1.000
14:23061140:A:T	F1215I	1.000
14:23061142:A:G	L1214P	1.000
14:23061142:A:T	L1214H	1.000
14:23061151:A:G	L1211P	1.000
14:23061151:A:T	L1211Q	1.000
14:23061160:G:T	A1208D	1.000
14:23061401:C:A	W1165C	1.000
14:23061401:C:G	W1165C	1.000
14:23061403:A:G	W1165R	1.000
14:23061403:A:T	W1165R	1.000
14:23061609:C:G	R1096P	1.000

dbSNP variants (sampled 300 via entrez): RS1000046308 (14:23064102 T>C), RS1000113709 (14:23074686 T>C), RS1000145646 (14:23058398 G>A), RS1000200489 (14:23070525 A>G), RS1000365059 (14:23058214 C>T), RS1000736301 (14:23073654 A>C), RS1000883684 (14:23095723 C>G,T), RS1000896021 (14:23085458 G>T), RS1000936687 (14:23069190 T>C), RS1000949332 (14:23085284 G>C), RS1001017570 (14:23092300 T>A), RS1001068227 (14:23085876 A>G), RS1001105117 (14:23091245 T>C), RS1001250862 (14:23071323 T>A,C), RS1001286486 (14:23069993 C>A,T)

Disease associations

OMIM: gene MIM:604562 | disease phenotypes: MIM:222700, MIM:245480

GenCC curated gene-disease

Mondo (2): lysinuric protein intolerance (MONDO:0009109), specific granule deficiency (MONDO:0009506)

Orphanet (2): Recurrent infections due to specific granule deficiency (Orphanet:169142), Lysinuric protein intolerance (Orphanet:470)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C562687	Lysinuric Protein Intolerance (supp.)
C562873	Specific Granule Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724741 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	MOLIBRESIB
7.64	Kd	23	nM	MOLIBRESIB
5.16	Kd	6971	nM	CHEMBL5653589
5.16	ED50	6971	nM	CHEMBL5653589

PubChem BioAssay actives

3 with measured affinity, of 9 total; 2 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178466: Inhibition of ACIN1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0200	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147783: Binding affinity to human ACIN1 incubated for 45 mins by Kinobead based pull down assay	kd	6.9708	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, affects cotreatment	3
Valproic Acid	decreases expression, decreases methylation, affects cotreatment, increases expression, affects expression	3
Aspirin	decreases expression, increases expression	2
Caffeine	affects phosphorylation, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
moringin	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
beauvericin	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
mono(2-ethyl-5-oxohexyl)phthalate	affects expression	1
CGP 52608	affects binding, increases reaction	1
panduratin A	increases degradation	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	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	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Cannabidiol	affects cotreatment, decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650825	Binding	Binding affinity to human ACIN1 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05706714	Not specified	COMPLETED	Th1, Th2, Th17 Phenotype in Urea Cycle Disorders