ACTR8

Summary

ACTR8 (actin related protein 8, HGNC:14672) is a protein-coding gene on chromosome 3p21.1, encoding Actin-related protein 8 (Q9H981). Plays an important role in the functional organization of mitotic chromosomes. It is a selective cancer dependency (DepMap: 62.9% of cell lines).

Predicted to enable ATP binding activity. Involved in several processes, including chromatin remodeling; regulation of chromosome organization; and regulation of nucleobase-containing compound metabolic process. Located in centrosome and nucleoplasm. Part of Ino80 complex.

Source: NCBI Gene 93973 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 129 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 62.9% of screened cell lines
• MANE Select transcript: NM_022899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14672
Approved symbol	ACTR8
Name	actin related protein 8
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Aliases	INO80N, ARP8
Ensembl gene	ENSG00000113812
Ensembl biotype	protein_coding
OMIM	619716
Entrez	93973

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000335754, ENST00000482349, ENST00000486794, ENST00000488802, ENST00000495993, ENST00000498740, ENST00000888052, ENST00000888053, ENST00000963856

RefSeq mRNA: 2 — MANE Select: NM_022899 NM_001410774, NM_022899

CCDS: CCDS2875, CCDS93290

Canonical transcript exons

ENST00000335754 — 13 exons

Exon	Start	End
ENSE00000771777	53875948	53876080
ENSE00000771780	53871232	53871496
ENSE00000771781	53869982	53870145
ENSE00000861051	53874211	53874364
ENSE00000861052	53873032	53873127
ENSE00001885871	53881979	53882152
ENSE00001957834	53867066	53868862
ENSE00002241867	53877214	53877387
ENSE00002301457	53877647	53877751
ENSE00003477594	53879939	53880109
ENSE00003492535	53876620	53876713
ENSE00003575248	53872384	53872524
ENSE00003619351	53878357	53878467

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 88.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1721 / max 195.1946, expressed in 1804 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42522	16.8281	1799
42523	0.7349	431
42520	0.6091	338

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	88.88	gold quality
islet of Langerhans	UBERON:0000006	87.75	gold quality
ganglionic eminence	UBERON:0004023	87.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.58	gold quality
left testis	UBERON:0004533	87.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.46	gold quality
cortical plate	UBERON:0005343	87.13	gold quality
right testis	UBERON:0004534	86.73	gold quality
testis	UBERON:0000473	86.46	gold quality
metanephros cortex	UBERON:0010533	86.34	gold quality
calcaneal tendon	UBERON:0003701	86.32	gold quality
adrenal tissue	UBERON:0018303	86.19	gold quality
granulocyte	CL:0000094	86.05	gold quality
rectum	UBERON:0001052	85.94	gold quality
sperm	CL:0000019	85.76	gold quality
body of pancreas	UBERON:0001150	85.65	gold quality
monocyte	CL:0000576	85.43	gold quality
apex of heart	UBERON:0002098	85.42	gold quality
right atrium auricular region	UBERON:0006631	85.34	gold quality
heart left ventricle	UBERON:0002084	85.27	gold quality
pancreas	UBERON:0001264	85.18	gold quality
cardiac ventricle	UBERON:0002082	85.17	gold quality
leukocyte	CL:0000738	85.13	gold quality
mononuclear cell	CL:0000842	85.10	gold quality
ventricular zone	UBERON:0003053	84.60	gold quality
heart	UBERON:0000948	84.41	gold quality
lymph node	UBERON:0000029	84.06	gold quality
lower esophagus mucosa	UBERON:0035834	83.96	gold quality
gall bladder	UBERON:0002110	83.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.70	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting ACTR8, 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-3646	100.00	73.56	5283
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-3913-3P	99.74	66.53	938

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 62.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Expression of truncated hArp8 proteins and depletion of endogenous hArp8 by RNA interference caused misalignment of mitotic chromosomes, suggesting that chromosome-associated hArp8 has a role in chromosome behavior. (PMID:18163988)
• These results suggest that ARP8 is required for the recruitment of the mammalian INO80 complex to the laser-induced DNA damage sites. (PMID:20971067)
• Binding studies reveal that Arp8 and the Arp8-Arp4-actin-HSA sub-complex of INO80 strongly prefer nucleosomes and H3-H4 tetramers over H2A-H2B dimers, suggesting that Arp8 functions as a nucleosome recognition module. (PMID:22977180)
• Plays a regulatory role in the binding of Arp8 to DNA. (PMID:25299602)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	actr8	ENSDARG00000103610
mus_musculus	Actr8	ENSMUSG00000015971
rattus_norvegicus	Actr8	ENSRNOG00000015280
drosophila_melanogaster	Arp8	FBGN0030877

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), ACTL6B (ENSG00000077080), ACTR5 (ENSG00000101442), ACTR3C (ENSG00000106526), ACTA2 (ENSG00000107796), ACTR1B (ENSG00000115073), ACTR3 (ENSG00000115091), ACTL8 (ENSG00000117148), ACTRT1 (ENSG00000123165), ACTR10 (ENSG00000131966), ACTR3B (ENSG00000133627), ACTL6A (ENSG00000136518), ACTR2 (ENSG00000138071), ACTR1A (ENSG00000138107), ACTA1 (ENSG00000143632), ACTL7B (ENSG00000148156), ACTC1 (ENSG00000159251), ACTG2 (ENSG00000163017), ACTBL2 (ENSG00000169067), ACTRT2 (ENSG00000169717), ACTL9 (ENSG00000181786), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Protein

Protein identifiers

Actin-related protein 8 — Q9H981 (reviewed: Q9H981)

Alternative names: INO80 complex subunit N

All UniProt accessions (3): C9J7L6, Q9H981, H0Y849

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the functional organization of mitotic chromosomes. Exhibits low basal ATPase activity, and unable to polymerize. Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Required for the recruitment of INO80 (and probably the INO80 complex) to sites of DNA damage. Strongly prefer nucleosomes and H3-H4 tetramers over H2A-H2B dimers, suggesting it may act as a nucleosome recognition module within the complex.

Subunit / interactions. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80. Interacts with ACTR5; the interaction is observed in asynchronous (interphase) cells but not in metaphase-arrested cells indicative for a possible dissociation of the INO80 complex in mitotic cells. Exists as monomers and dimers, but the dimer is most probably the biologically relevant form required for stable interactions with histones that exploits the twofold symmetry of the nucleosome core.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the actin family. ARP8 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H981-1	1	yes
Q9H981-2	2
Q9H981-3	3

RefSeq proteins (2): NP_001397703, NP_075050* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004000	Actin	Family
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022

UniProt features (61 total): helix 24, strand 18, turn 4, splice variant 3, binding site 3, modified residue 3, region of interest 2, chain 1, sequence variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4FO0	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H981-F1	87.30	0.78

Functional residue map

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

Ligand- & substrate-binding residues (3): 55; 56; 283–286

Post-translational modifications (3): 1, 132, 412

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5689603	UCH proteinases
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-5696398	Nucleotide Excision Repair
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-597592	Post-translational protein modification
R-HSA-73894	DNA Repair

MSigDB gene sets: 125 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR, GGCNKCCATNK_UNKNOWN, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, YY1_02, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_STRAND_ELONGATION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR, GOBP_POSITIVE_REGULATION_OF_TELOMERE_MAINTENANCE

GO Biological Process (20): telomere maintenance (GO:0000723), regulation of DNA replication (GO:0006275), regulation of DNA repair (GO:0006282), double-strand break repair (GO:0006302), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of chromosome organization (GO:0033044), positive regulation of DNA repair (GO:0045739), positive regulation of DNA-templated transcription (GO:0045893), regulation of embryonic development (GO:0045995), cell division (GO:0051301), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), DNA repair (GO:0006281), DNA damage response (GO:0006974), positive regulation of macromolecule metabolic process (GO:0010604), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935), regulation of DNA metabolic process (GO:0051052)

GO Molecular Function (3): ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), Ino80 complex (GO:0031011), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Deubiquitination	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Post-translational protein modification	1
DNA Repair	1
Nucleotide Excision Repair	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	4
regulation of DNA metabolic process	3
DNA repair	3
DNA-templated transcription	2
positive regulation of response to stimulus	2
regulation of macromolecule metabolic process	2
telomere organization	1
DNA replication	1
regulation of cellular response to stress	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of organelle organization	1
chromosome organization	1
regulation of DNA repair	1
positive regulation of DNA metabolic process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
embryo development	1
regulation of multicellular organismal development	1
cellular process	1
cell cycle	1
regulation of cellular process	1
DNA strand elongation	1
positive regulation of telomere maintenance	1
telomere maintenance in response to DNA damage	1
regulation of telomere maintenance in response to DNA damage	1
DNA damage response	1
cellular response to stress	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2589 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACTR8	RUVBL1	P82276	822
ACTR8	ACTR5	Q9H9F9	798
ACTR8	RUVBL2	Q9Y230	779
ACTR8	K7ENP7	K7ENP7	744
ACTR8	INO80C	Q6PI98	744
ACTR8	NFRKB	Q6P4R8	627
ACTR8	INO80B	Q9C086	575
ACTR8	INO80	Q9ULG1	459
ACTR8	ATPAF2	Q8N5M1	456
ACTR8	SRCAP	Q6ZRS2	454
ACTR8	TFPT	P0C1Z6	452
ACTR8	ANKRD45	Q5TZF3	432
ACTR8	RCBTB1	Q8NDN9	432
ACTR8	INO80E	Q8NBZ0	427
ACTR8	SPC24	Q8NBT2	424

IntAct

65 interactions, top by confidence:

A	B	Type	Score
INO80E	YY1	psi-mi:“MI:0914”(association)	0.900
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
YY1	ACTL6A	psi-mi:“MI:0914”(association)	0.830
INO80E	TFPT	psi-mi:“MI:0914”(association)	0.790
YY1	TFPT	psi-mi:“MI:0914”(association)	0.740
INO80C	YY1	psi-mi:“MI:0914”(association)	0.740
ACTR8	UCHL5	psi-mi:“MI:0915”(physical association)	0.710
ACTR8	ACTR5	psi-mi:“MI:0915”(physical association)	0.670
INO80E	ACTL6A	psi-mi:“MI:0914”(association)	0.640
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
YY1	YY2	psi-mi:“MI:0914”(association)	0.570
ACTR8	INO80B	psi-mi:“MI:0914”(association)	0.530
Cep78	ING5	psi-mi:“MI:0914”(association)	0.350
Ruvbl1	AAR2	psi-mi:“MI:0914”(association)	0.350
Ruvbl2	TTI2	psi-mi:“MI:0914”(association)	0.350
SGTB	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
BAG6	CNOT1	psi-mi:“MI:0914”(association)	0.350
ACTR5	TBRG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (130): DCAF10 (Affinity Capture-MS), AMY1C (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), NFRKB (Co-fractionation), ACTR8 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS), RUVBL2 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS), ACTR8 (Affinity Capture-MS)

ESM2 similar proteins: A4D1U4, A4IJ06, A6QNT4, B5X2S3, D2I1E3, F1M5F3, F1N2W9, F1QDI9, I0IUP4, O88910, O88954, P50747, P52633, P55266, P59679, P97616, Q05AA6, Q09M05, Q0IEG8, Q0PGW2, Q12767, Q13474, Q14164, Q1LZF2, Q2KHI9, Q2YDD2, Q3UHG7, Q496Y0, Q4U2V3, Q5RDA1, Q641K1, Q69ZK0, Q6NTL4, Q6ZT62, Q7ZU92, Q8HXH0, Q8K2I9, Q8NFZ0, Q8R2S9, Q8TCU6

Diamond homologs: A5DQP9, B5X2S3, D2I1E3, O74258, P14235, P17128, P45891, P59679, P60009, P60010, P60011, Q09849, Q0IEG8, Q1LZF2, Q29G73, Q54JV5, Q5RDA1, Q75D00, Q8R2S9, Q9H981, Q9P4D1, Q9UVF3, Q9UVZ8, Q9VX09, A2XLF2, A3C6D7, P02580, P0C539, P0C540, P0C542, P0CJ46, P0CJ47, P10988, P10990, P10992, P10993, P11426, P12432, P12433, P18602

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ACTR8	“form complex”	“INO80 complex”	binding
ATM	“down-regulates activity”	ACTR8	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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
Global Genome Nucleotide Excision Repair (GG-NER)	11	132.2×	1e-19
Formation of the canonical BAF (cBAF) complex	6	100.2×	6e-10
DNA Damage Recognition in GG-NER	12	90.2×	2e-19
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	7	84.2×	5e-11
Nucleotide Excision Repair	11	82.6×	2e-17
Formation of the embryonic stem cell BAF (esBAF) complex	5	79.1×	1e-07
Regulation of endogenous retroelements	5	48.5×	1e-06
UCH proteinases	14	45.7×	1e-18

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance in response to DNA damage	13	251.8×	8e-29
regulation of DNA strand elongation	13	236.1×	2e-28
regulation of chromosome organization	13	209.8×	2e-27
regulation of DNA replication	14	88.4×	9e-23
positive regulation of DNA repair	14	86.5×	1e-22
regulation of G0 to G1 transition	7	81.3×	5e-11
regulation of embryonic development	14	79.8×	3e-22
regulation of nucleotide-excision repair	7	72.6×	1e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1783 predictions. Top by Δscore:

Variant	Effect	Δscore
3:53871230:A:AC	donor_gain	1.0000
3:53871231:C:CC	donor_gain	1.0000
3:53871231:CAA:C	donor_gain	1.0000
3:53871281:T:A	donor_gain	1.0000
3:53871307:T:TA	donor_gain	1.0000
3:53871390:T:TA	donor_gain	1.0000
3:53871493:CAGA:C	acceptor_gain	1.0000
3:53871497:C:CC	acceptor_gain	1.0000
3:53871498:T:C	acceptor_gain	1.0000
3:53871505:C:CT	acceptor_gain	1.0000
3:53871506:A:T	acceptor_gain	1.0000
3:53872379:CGGA:C	donor_loss	1.0000
3:53872380:GGA:G	donor_loss	1.0000
3:53872520:GGAGC:G	acceptor_gain	1.0000
3:53872521:GAGC:G	acceptor_gain	1.0000
3:53872522:AGC:A	acceptor_gain	1.0000
3:53872523:GC:G	acceptor_gain	1.0000
3:53872523:GCCTG:G	acceptor_loss	1.0000
3:53872524:CCTG:C	acceptor_gain	1.0000
3:53872525:C:CC	acceptor_gain	1.0000
3:53872525:CT:C	acceptor_loss	1.0000
3:53872527:G:C	acceptor_gain	1.0000
3:53872530:CA:C	acceptor_gain	1.0000
3:53872531:A:C	acceptor_gain	1.0000
3:53873135:C:CT	acceptor_gain	1.0000
3:53875944:TTACC:T	donor_loss	1.0000
3:53875945:TA:T	donor_loss	1.0000
3:53875946:A:AC	donor_gain	1.0000
3:53875947:C:CT	donor_gain	1.0000
3:53876076:AATCC:A	acceptor_gain	1.0000

AlphaMissense

4096 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:53874239:A:G	L346P	1.000
3:53868724:A:G	W624R	0.999
3:53868724:A:T	W624R	0.999
3:53868790:A:G	W602R	0.999
3:53868790:A:T	W602R	0.999
3:53868832:C:G	G588R	0.999
3:53868832:C:T	G588R	0.999
3:53868838:A:G	W586R	0.999
3:53868838:A:T	W586R	0.999
3:53870061:A:G	L551P	0.999
3:53871245:G:C	S518R	0.999
3:53871245:G:T	S518R	0.999
3:53871247:T:G	S518R	0.999
3:53871259:C:G	A514P	0.999
3:53872490:C:T	G399E	0.999
3:53872523:G:T	A388D	0.999
3:53874235:T:A	K347N	0.999
3:53874235:T:G	K347N	0.999
3:53874314:A:G	L321P	0.999
3:53874347:C:A	G310V	0.999
3:53874347:C:T	G310E	0.999
3:53876019:A:C	C280W	0.999
3:53877264:A:G	W212R	0.999
3:53877264:A:T	W212R	0.999
3:53878380:G:T	R128S	0.999
3:53878436:C:T	G109D	0.999
3:53878437:C:G	G109R	0.999
3:53880006:G:T	A76D	0.999
3:53868738:C:G	R619P	0.998
3:53868744:C:G	R617P	0.998

dbSNP variants (sampled 300 via entrez): RS1000007560 (3:53866228 T>TA), RS1000200108 (3:53880201 C>A,T), RS1000438448 (3:53868766 G>A,C), RS1000532778 (3:53878554 G>A), RS1000782666 (3:53862706 T>C), RS1000869919 (3:53884060 G>A), RS1001064326 (3:53864374 A>G), RS1001328332 (3:53860025 TAAAA>T,TAA,TAAA,TAAAAA), RS1001355464 (3:53880306 G>A,C), RS1001550079 (3:53862461 T>C), RS1001689977 (3:53873592 A>C), RS1001703495 (3:53880664 T>A), RS1001763598 (3:53874114 G>A), RS1001880752 (3:53863771 T>A), RS1001934906 (3:53863396 A>G)

Disease associations

OMIM: gene MIM:619716 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002115_6	Axial length	8.000000e-06
GCST005951_50	Body mass index	5.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725020 (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

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
7.24	Kd	57	nM	MOLIBRESIB
7.10	IC50	80	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179227: Binding affinity against ACTR8 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0570	uM

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Ozone	increases abundance, affects expression, affects cotreatment, increases oxidation	2
Valproic Acid	affects expression, decreases methylation	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
CGP 52608	affects binding, increases reaction	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Quercetin	decreases phosphorylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697645	Binding	Inhibition of ACTR8 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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