ACTR5

Summary

ACTR5 (actin related protein 5, HGNC:14671) is a protein-coding gene on chromosome 20q11.23, encoding Actin-related protein 5 (Q9H9F9). Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. It is a selective cancer dependency (DepMap: 20.4% of cell lines).

Involved in several processes, including DNA repair; chromatin remodeling; and regulation of nucleobase-containing compound metabolic process. Located in cytoplasm and nucleus. Part of Ino80 complex.

Source: NCBI Gene 79913 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 94 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 20.4% of screened cell lines
• MANE Select transcript: NM_024855

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14671
Approved symbol	ACTR5
Name	actin related protein 5
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12785, Arp5, INO80M
Ensembl gene	ENSG00000101442
Ensembl biotype	protein_coding
OMIM	619730
Entrez	79913

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000243903, ENST00000917421, ENST00000917422

RefSeq mRNA: 1 — MANE Select: NM_024855 NM_024855

CCDS: CCDS13308

Canonical transcript exons

ENST00000243903 — 9 exons

Exon	Start	End
ENSE00000661974	38750010	38750239
ENSE00000661975	38752131	38752300
ENSE00000661977	38755857	38756039
ENSE00000661978	38765402	38765518
ENSE00000661979	38766238	38766377
ENSE00000844672	38748460	38748853
ENSE00000844678	38767464	38767596
ENSE00000844679	38771559	38772520
ENSE00001338878	38754957	38755174

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 87.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7799 / max 85.4880, expressed in 1734 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184585	7.7799	1734

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hair follicle	UBERON:0002073	87.66	silver quality
tongue squamous epithelium	UBERON:0006919	87.30	silver quality
olfactory bulb	UBERON:0002264	87.07	gold quality
cervix squamous epithelium	UBERON:0006922	84.88	silver quality
type B pancreatic cell	CL:0000169	84.12	gold quality
gingival epithelium	UBERON:0001949	84.06	gold quality
saphenous vein	UBERON:0007318	83.98	gold quality
granulocyte	CL:0000094	83.31	gold quality
mucosa of urinary bladder	UBERON:0001259	83.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.09	gold quality
epithelial cell of pancreas	CL:0000083	82.69	silver quality
male germ cell	CL:0000015	81.58	silver quality
superior surface of tongue	UBERON:0007371	81.52	gold quality
tongue	UBERON:0001723	81.41	silver quality
vena cava	UBERON:0004087	81.27	gold quality
sperm	CL:0000019	81.09	silver quality
thymus	UBERON:0002370	81.07	silver quality
pylorus	UBERON:0001166	81.02	gold quality
cardia of stomach	UBERON:0001162	80.98	silver quality
nipple	UBERON:0002030	80.79	gold quality
tendon of biceps brachii	UBERON:0008188	80.75	silver quality
pharyngeal mucosa	UBERON:0000355	80.74	silver quality
epithelium of nasopharynx	UBERON:0001951	80.64	gold quality
gingiva	UBERON:0001828	80.63	gold quality
endothelial cell	CL:0000115	80.60	silver quality
right testis	UBERON:0004534	80.21	gold quality
left testis	UBERON:0004533	80.10	gold quality
pericardium	UBERON:0002407	79.79	silver quality
testis	UBERON:0000473	79.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, YY1

miRNA regulators (miRDB)

15 targeting ACTR5, 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-513A-5P	100.00	69.77	2465
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-3943	95.87	64.57	523

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Arp5 is involved in the process of DNA double strand break repair through the regulation of the chromatin remodelling machinery. (PMID:19014934)
• Arp5 is a key regulator of Myocd activity. (PMID:24567363)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	actr5	ENSDARG00000098235
mus_musculus	Actr5	ENSMUSG00000037761
rattus_norvegicus	Actr5	ENSRNOG00000023989
drosophila_melanogaster	Arp5	FBGN0038576

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), ACTL6B (ENSG00000077080), ACTR3C (ENSG00000106526), ACTA2 (ENSG00000107796), ACTR8 (ENSG00000113812), 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 5 — Q9H9F9 (reviewed: Q9H9F9)

Alternative names: Sarcoma antigen NY-SAR-16

All UniProt accessions (1): Q9H9F9

UniProt curated annotations — full annotation on UniProt →

Function. Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Involved in DNA double-strand break repair and UV-damage excision repair.

Subunit / interactions. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Interacts with DDB1. Interacts with ACTR8; 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.

Subcellular location. Nucleus. Cytoplasm.

Similarity. Belongs to the actin family. ARP5 subfamily.

RefSeq proteins (1): NP_079131* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004000	Actin	Family
IPR004001	Actin_CS	Conserved_site
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022

UniProt features (13 total): sequence variant 4, sequence conflict 2, coiled-coil region 2, compositionally biased region 2, chain 1, region of interest 1, cross-link 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7ZI4	ELECTRON MICROSCOPY	3.2
9GE5	ELECTRON MICROSCOPY	3.35
9GCG	ELECTRON MICROSCOPY	3.43
9GEV	ELECTRON MICROSCOPY	3.47
9GFB	ELECTRON MICROSCOPY	3.55
6HTS	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9F9-F1	83.75	0.62

Functional residue map

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

Post-translational modifications (1): 283

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: 97 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, MODULE_205, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_RESPONSE_TO_UV, GOBP_DNA_STRAND_ELONGATION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR

GO Biological Process (21): 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), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), UV-damage excision repair (GO:0070914), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), DNA metabolic process (GO:0006259), 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 (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Ino80 complex (GO:0031011)

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 repair	4
DNA metabolic process	3
regulation of DNA metabolic process	3
DNA-templated transcription	2
positive regulation of response to stimulus	2
cellular anatomical structure	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
cell cycle	1
regulation of cellular process	1
DNA strand elongation	1
cellular response to UV	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
nucleic acid metabolic process	1
DNA damage response	1
cellular response to stress	1
positive regulation of metabolic process	1
macromolecule metabolic process	1
regulation of macromolecule metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear chromosome	1
INO80-type complex	1

Protein interactions and networks

STRING

1228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACTR5	K7ENP7	K7ENP7	833
ACTR5	INO80C	Q6PI98	833
ACTR5	RUVBL1	P82276	822
ACTR5	NFRKB	Q6P4R8	806
ACTR5	ACTR8	Q9H981	798
ACTR5	RUVBL2	Q9Y230	743
ACTR5	UCHL5	Q9Y5K5	533
ACTR5	TFPT	P0C1Z6	500
ACTR5	INO80B	Q9C086	471
ACTR5	RFFL	Q8WZ73	435
ACTR5	INO80	Q9ULG1	428
ACTR5	MED27	Q6P2C8	420
ACTR5	XPA	P23025	414
ACTR5	RNF34	Q969K3	410
ACTR5	ERCC6	Q03468	408

IntAct

91 interactions, top by confidence:

A	B	Type	Score
INO80E	YY1	psi-mi:“MI:0914”(association)	0.900
INO80	ACTR5	psi-mi:“MI:0915”(physical association)	0.880
ACTR5	INO80	psi-mi:“MI:0915”(physical association)	0.880
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
UCHL5	PSMD11	psi-mi:“MI:0914”(association)	0.840
UCHL5	PSMD12	psi-mi:“MI:0914”(association)	0.840
YY1	ACTL6A	psi-mi:“MI:0914”(association)	0.830
RUVBL2	ZNHIT1	psi-mi:“MI:0914”(association)	0.810
INO80E	TFPT	psi-mi:“MI:0914”(association)	0.790
INO80C	YY1	psi-mi:“MI:0914”(association)	0.740
ACTR8	ACTR5	psi-mi:“MI:0915”(physical association)	0.670
ACTR5	INO80C	psi-mi:“MI:0915”(physical association)	0.670
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
INO80E	ACTL6A	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640

BioGRID (140): ACTR5 (Affinity Capture-MS), ACTR5 (Affinity Capture-MS), ACTR5 (Co-fractionation), ACTR5 (Co-fractionation), INO80 (Co-fractionation), ACTR5 (Synthetic Growth Defect), ACTL6A (Affinity Capture-MS), KLF5 (Affinity Capture-MS), FMNL1 (Affinity Capture-MS), EIF4G1 (Affinity Capture-MS), NFRKB (Affinity Capture-MS), PPM1A (Affinity Capture-MS), YY1 (Affinity Capture-MS), ZNF148 (Affinity Capture-MS), RUVBL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A2AGL3, B0LPN4, B5X2S3, D2I1E3, I3LHK5, O43929, O60733, O94844, P0C7A6, P42694, P97570, P97819, Q05B56, Q13889, Q15413, Q1LVW0, Q1LZF2, Q2KJA6, Q32PW3, Q3ZBD2, Q4R5Z4, Q561R7, Q5F361, Q5F477, Q5FVD6, Q5R6Z7, Q5RDA1, Q5ZKK2, Q63616, Q6NRC7, Q7SXV1, Q80US4, Q80YV4, Q84M92, Q8BHL5, Q8BM85, Q8K0F1, Q8K114, Q8R2S9

Diamond homologs: A2WKK5, A2XLF2, A2XNS1, A2ZP58, A3C6D7, D0LWX4, O16808, O18499, O65314, O65315, O65316, O81221, P02576, P04751, P07828, P07830, P07836, P07837, P08023, P0C539, P0C540, P0C542, P0CJ46, P0CJ47, P10981, P12716, P12717, P17126, P17304, P18601, P23343, P24902, P30162, P30164, P30165, P30167, P30168, P30169, P30171, P30172

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ACTR5	“form complex”	“INO80 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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	116.9×	3e-19
DNA Damage Recognition in GG-NER	14	93.0×	4e-23
Formation of the canonical BAF (cBAF) complex	5	73.8×	2e-07
Nucleotide Excision Repair	11	73.0×	1e-16
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	6	63.7×	2e-08
UCH proteinases	17	49.1×	4e-23
Deubiquitination	11	31.8×	2e-12
Regulation of MITF-M-dependent genes involved in pigmentation	5	30.9×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance in response to DNA damage	14	245.8×	1e-31
regulation of DNA strand elongation	14	230.4×	6e-31
regulation of chromosome organization	14	204.8×	1e-29
positive regulation of DNA repair	16	89.6×	3e-26
regulation of DNA replication	14	80.1×	3e-22
regulation of embryonic development	14	72.3×	2e-21
DNA recombination	12	63.2×	1e-17
regulation of G0 to G1 transition	6	63.2×	9e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1329 predictions. Top by Δscore:

Variant	Effect	Δscore
20:38748850:ACAGG:A	donor_loss	1.0000
20:38748852:AGGTG:A	donor_loss	1.0000
20:38748853:GG:G	donor_loss	1.0000
20:38748854:G:A	donor_loss	1.0000
20:38750207:GT:G	donor_gain	1.0000
20:38752129:A:AG	acceptor_gain	1.0000
20:38752130:G:GG	acceptor_gain	1.0000
20:38752130:GATTA:G	acceptor_gain	1.0000
20:38752288:GAT:G	donor_gain	1.0000
20:38752295:TGGA:T	donor_gain	1.0000
20:38752296:GGAA:G	donor_gain	1.0000
20:38752297:G:GT	donor_gain	1.0000
20:38752297:GAAG:G	donor_gain	1.0000
20:38752297:GAAGG:G	donor_loss	1.0000
20:38752298:A:T	donor_gain	1.0000
20:38752300:GGTAT:G	donor_loss	1.0000
20:38752301:GT:G	donor_loss	1.0000
20:38752312:G:GT	donor_gain	1.0000
20:38754939:A:AG	acceptor_gain	1.0000
20:38754940:A:G	acceptor_gain	1.0000
20:38754952:T:TA	acceptor_gain	1.0000
20:38754955:A:AG	acceptor_gain	1.0000
20:38754956:G:GG	acceptor_gain	1.0000
20:38754956:GA:G	acceptor_gain	1.0000
20:38754956:GAAT:G	acceptor_gain	1.0000
20:38755172:CAG:C	donor_gain	1.0000
20:38755173:AGG:A	donor_loss	1.0000
20:38755174:GGTAA:G	donor_loss	1.0000
20:38755175:G:GA	donor_loss	1.0000
20:38755176:T:G	donor_loss	1.0000

AlphaMissense

3959 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:38755161:T:C	L327P	1.000
20:38755933:T:C	L357P	1.000
20:38755095:T:C	L305P	0.999
20:38755116:G:C	R312P	0.999
20:38755152:T:C	L324P	0.999
20:38755900:T:C	L346P	0.999
20:38755954:T:C	L364P	0.999
20:38750079:T:C	S149P	0.998
20:38750086:T:C	L151P	0.998
20:38750091:T:C	F153L	0.998
20:38750093:T:A	F153L	0.998
20:38750093:T:G	F153L	0.998
20:38750142:A:C	S170R	0.998
20:38750144:C:A	S170R	0.998
20:38750144:C:G	S170R	0.998
20:38752154:G:C	R210P	0.998
20:38752199:T:C	L225P	0.998
20:38752202:T:C	L226P	0.998
20:38752208:T:C	L228P	0.998
20:38755014:T:C	L278P	0.998
20:38755092:G:C	R304P	0.998
20:38755109:G:C	A310P	0.998
20:38755119:G:C	R313P	0.998
20:38755131:T:C	L317P	0.998
20:38766269:T:C	L442P	0.998
20:38771592:T:A	W534R	0.998
20:38771592:T:C	W534R	0.998
20:38750068:G:C	R145P	0.997
20:38750091:T:A	F153I	0.997
20:38752153:C:A	R210S	0.997

dbSNP variants (sampled 300 via entrez): RS1000023887 (20:38747277 A>T), RS1000084184 (20:38748095 C>G), RS1000089273 (20:38753347 C>T), RS1000176750 (20:38747929 T>C), RS1000383968 (20:38754266 G>A,T), RS1000397709 (20:38760316 C>T), RS1000428736 (20:38760584 C>A), RS1000624031 (20:38748464 G>A,C), RS1000730055 (20:38758758 T>C), RS1000758626 (20:38759070 T>G), RS1000842449 (20:38765262 A>T), RS1001120890 (20:38752744 A>G), RS1001230756 (20:38764846 T>A), RS1001336823 (20:38765003 T>A,G), RS1001441522 (20:38747143 T>C)

Disease associations

OMIM: gene MIM:619730 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002539_92	Schizophrenia	1.000000e-11
GCST004521_49	Autism spectrum disorder or schizophrenia	1.000000e-09
GCST004938_1	Liver fibrosis in pediatric non-alcoholic fatty acid liver disease	1.000000e-06
GCST006803_7	Schizophrenia	8.000000e-17
GCST009600_55	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	1.000000e-09
GCST012490_220	Femur bone mineral density x serum urate levels interaction	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725012 (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
7.19	Kd	65	nM	MOLIBRESIB
6.92	IC50	120	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	2179237: Binding affinity against ACTR5 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0650	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
sodium arsenite	decreases expression	1
monomethylarsonous acid	decreases expression	1
abrine	increases expression	1
Leflunomide	decreases expression	1
Cadmium	increases abundance, increases expression	1
Cannabidiol	decreases expression	1
Clozapine	affects cotreatment, increases expression	1
Cuprizone	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	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
CHEMBL5697716	Binding	Inhibition of ACTR5 (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)

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

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia