ACR

Summary

ACR (acrosin, HGNC:126) is a protein-coding gene on chromosome 22q13.33, encoding Acrosin (P10323). Acrosin is the major protease of mammalian spermatozoa.

Acrosin is the major proteinase present in the acrosome of mature spermatozoa. It is a typical serine proteinase with trypsin-like specificity. It is stored in the acrosome in its precursor form, proacrosin. The active enzyme functions in the lysis of the zona pellucida, thus facilitating penetration of the sperm through the innermost glycoprotein layers of the ovum. The mRNA for proacrosin is synthesized only in the postmeiotic stages of spermatogenesis. In humans proacrosin first appears in the haploid spermatids.

Source: NCBI Gene 49 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 199 total — 103 pathogenic
• GTEx eGene: eQTL in 21 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 4
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.94 (unconstrained)
• MANE Select transcript: NM_001097
• Notable: 199 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:126
Approved symbol	ACR
Name	acrosin
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100312
Ensembl biotype	protein_coding
OMIM	102480
Entrez	49

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000216139

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 5: 2

ENST00000216139, ENST00000527761, ENST00000529621, ENST00000533930, ENST00001130073, ENST00001135378

RefSeq mRNA: 1 — MANE Select: NM_001097 NM_001097

CCDS: CCDS14101

Canonical transcript exons

ENST00000216139 — 5 exons

Exon	Start	End
ENSE00000657865	50744061	50744206
ENSE00000935813	50739694	50739977
ENSE00001294892	50744653	50745339
ENSE00003676371	50738204	50738312
ENSE00003680460	50739271	50739474

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 95.94.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3868 / max 396.0526, expressed in 4 samples.

Highest expression (Bgee): testis, male germ line stem cell (sensu Vertebrata) in testis, subcutaneous adipose tissue, mucosa of stomach, spleen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 24 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Prostate	sqtl	5.8e-08	+0.53	22:50723631:G:A
Skin Sun Exposed Lower leg	eqtl	1.0e-07	-0.18	22:50733265:G:A
Testis	sqtl	3.3e-06	-0.41	22:50744589:C:T
Colon Sigmoid	eqtl	4.4e-06	-0.31	22:50733265:G:A
Adipose Subcutaneous	eqtl	1.0e-05	-0.16	22:50718238:C:T
Nerve Tibial	eqtl	3.7e-05	-0.18	22:50733265:G:A
Brain Nucleus accumbens basal ganglia	eqtl	1.2e-04	-0.34	22:50733265:G:A
Esophagus Muscularis	eqtl	9.4e-04	-0.18	22:50204348:C:T
Muscle Skeletal	eqtl	1.4e-03	-0.16	22:50733265:G:A
Skin Not Sun Exposed Suprapubic	eqtl	2.9e-03	-0.16	22:50733265:G:A
Adipose Visceral Omentum	eqtl	4.1e-03	-0.71	22:50738115:C:T
Brain Caudate basal ganglia	eqtl	4.2e-03	-0.28	22:50733265:G:A
Pituitary	eqtl	1.5e-02	-0.27	22:50733265:G:A
Brain Frontal Cortex BA9	eqtl	1.7e-02	-0.33	22:50733265:G:A
Lung	eqtl	2.1e-02	+0.13	22:50712343:A:G
Spleen	eqtl	3.0e-02	-0.20	22:50733265:G:A
Uterus	eqtl	3.1e-02	+2.58	22:49774617:G:A
Heart Left Ventricle	eqtl	3.5e-02	-0.76	22:50738115:C:T
Brain Cortex	eqtl	3.7e-02	-0.30	22:50716723:T:C
Adrenal Gland	eqtl	4.2e-02	-0.28	22:50743491:G:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
193055	0.3868	4

Top tissues by expression

showing 100 of 132 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.94	gold quality
testis	UBERON:0000473	95.75	gold quality
right testis	UBERON:0004534	95.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.52	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.89	gold quality
mucosa of stomach	UBERON:0001199	73.87	gold quality
spleen	UBERON:0002106	72.55	gold quality
upper lobe of left lung	UBERON:0008952	72.28	gold quality
right lung	UBERON:0002167	72.05	gold quality
adipose tissue	UBERON:0001013	72.00	gold quality
thoracic mammary gland	UBERON:0005200	70.91	gold quality
gastrocnemius	UBERON:0001388	68.58	gold quality
apex of heart	UBERON:0002098	68.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.24	gold quality
left uterine tube	UBERON:0001303	67.79	gold quality
omental fat pad	UBERON:0010414	67.59	gold quality
muscle of leg	UBERON:0001383	66.90	gold quality
ectocervix	UBERON:0012249	66.28	gold quality
right uterine tube	UBERON:0001302	66.03	gold quality
skin of leg	UBERON:0001511	65.71	gold quality
tibial nerve	UBERON:0001323	64.85	gold quality
body of uterus	UBERON:0009853	64.70	gold quality
zone of skin	UBERON:0000014	64.49	gold quality
myometrium	UBERON:0001296	64.28	gold quality
skin of abdomen	UBERON:0001416	63.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.26	gold quality
lower esophagus	UBERON:0013473	63.23	gold quality
lung	UBERON:0002048	63.21	gold quality
cortex of kidney	UBERON:0001225	63.07	gold quality
fallopian tube	UBERON:0003889	62.52	gold quality
heart left ventricle	UBERON:0002084	62.30	gold quality
sural nerve	UBERON:0015488	62.27	gold quality
metanephros cortex	UBERON:0010533	62.07	gold quality
uterine cervix	UBERON:0000002	61.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.68	gold quality
vagina	UBERON:0000996	61.43	gold quality
saliva-secreting gland	UBERON:0001044	61.42	gold quality
minor salivary gland	UBERON:0001830	61.33	gold quality
right lobe of liver	UBERON:0001114	60.89	gold quality
smooth muscle tissue	UBERON:0001135	60.82	gold quality
tibial artery	UBERON:0007610	60.65	gold quality
putamen	UBERON:0001874	60.61	gold quality
popliteal artery	UBERON:0002250	60.36	gold quality
endocervix	UBERON:0000458	59.89	gold quality
left lobe of thyroid gland	UBERON:0001120	59.61	gold quality
esophagus	UBERON:0001043	59.58	gold quality
thyroid gland	UBERON:0002046	59.49	gold quality
adult mammalian kidney	UBERON:0000082	59.41	gold quality
heart	UBERON:0000948	59.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	59.32	gold quality
right atrium auricular region	UBERON:0006631	59.18	gold quality
caudate nucleus	UBERON:0001873	58.97	gold quality
multicellular organism	UBERON:0000468	58.87	gold quality
left coronary artery	UBERON:0001626	58.79	gold quality
nucleus accumbens	UBERON:0001882	58.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	58.46	gold quality
mucosa of transverse colon	UBERON:0004991	58.34	gold quality
prostate gland	UBERON:0002367	58.21	gold quality
transverse colon	UBERON:0001157	58.13	gold quality
prefrontal cortex	UBERON:0000451	58.03	gold quality
right lobe of thyroid gland	UBERON:0001119	57.88	gold quality
right coronary artery	UBERON:0001625	57.68	gold quality
kidney	UBERON:0002113	57.30	gold quality
muscle tissue	UBERON:0002385	57.22	gold quality
colon	UBERON:0001155	57.05	gold quality
frontal cortex	UBERON:0001870	56.96	gold quality
adenohypophysis	UBERON:0002196	56.93	gold quality
lower esophagus mucosa	UBERON:0035834	56.75	gold quality
esophagus mucosa	UBERON:0002469	56.73	gold quality
pituitary gland	UBERON:0000007	56.69	gold quality
liver	UBERON:0002107	56.63	gold quality
descending thoracic aorta	UBERON:0002345	56.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	56.25	gold quality
skeletal muscle tissue	UBERON:0001134	56.16	gold quality
right frontal lobe	UBERON:0002810	55.99	gold quality
primary visual cortex	UBERON:0002436	55.80	gold quality
intestine	UBERON:0000160	55.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	55.62	gold quality
brain	UBERON:0000955	55.02	gold quality
fundus of stomach	UBERON:0001160	54.86	gold quality
superior frontal gyrus	UBERON:0002661	54.80	gold quality
amygdala	UBERON:0001876	54.63	gold quality
cerebral cortex	UBERON:0000956	54.58	gold quality
gall bladder	UBERON:0002110	54.42	gold quality
temporal lobe	UBERON:0001871	54.26	gold quality
ascending aorta	UBERON:0001496	54.06	gold quality
thoracic aorta	UBERON:0001515	53.95	gold quality
small intestine	UBERON:0002108	53.85	gold quality
anterior cingulate cortex	UBERON:0009835	53.81	gold quality
substantia nigra	UBERON:0002038	53.62	gold quality
hypothalamus	UBERON:0001898	53.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	53.51	gold quality
Ammon’s horn	UBERON:0001954	53.13	gold quality
right ovary	UBERON:0002118	53.13	gold quality
rectum	UBERON:0001052	53.06	gold quality
tonsil	UBERON:0002372	53.01	silver quality
right adrenal gland cortex	UBERON:0035827	52.98	gold quality
body of stomach	UBERON:0001161	52.78	gold quality
cerebellar cortex	UBERON:0002129	52.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	52.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.20

HPA expression

RNA tissue specificity: Tissue enriched

59 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	29.2	high
Choroid plexus	tissue	5.0
Caudate putamen	tissue	1.1
Epididymis	tissue	0.7	not detected
Spleen	tissue	0.7	not detected
Vagina	tissue	0.6	not detected
Frontal cortex	tissue	0.6
Nucleus accumbens	tissue	0.6
Pituitary gland	tissue	0.5
Postcentral gyrus	tissue	0.5
Periaqueductal gray	tissue	0.5
Adipose tissue	tissue	0.4	not detected
Salivary gland	tissue	0.4	not detected
Fallopian tube	tissue	0.4	not detected
Cerebral cortex	tissue	0.3	not detected
Basal ganglia	tissue	0.3	not detected
Hypothalamus	tissue	0.3
Locus coeruleus	tissue	0.3
Hippocampus	tissue	0.3	not detected
Retrosplenial cortex	tissue	0.3
Temporal cortex	tissue	0.3
Occipital cortex	tissue	0.3
Skin 1	tissue	0.2	not detected
Heart muscle	tissue	0.2	not detected
Seminal vesicle	tissue	0.2	not detected
Skeletal muscle	tissue	0.2	not detected
Endometrium 1	tissue	0.2	not detected
Putamen	tissue	0.2
Medulla oblongata	tissue	0.2
Superior colliculi	tissue	0.2
Cerebellum	tissue	0.2	not detected
Lung	tissue	0.2	not detected
Liver	tissue	0.2	not detected
Gallbladder	tissue	0.2	not detected
Kidney	tissue	0.2	not detected
Hippocampal formation	tissue	0.2
Entorhinal cortex	tissue	0.2
Ventral forebrain	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Olfactory bulb	tissue	0.2
Septum	tissue	0.2
Somatosensory cortex	tissue	0.2
Insular cortex	tissue	0.2
Cervix	tissue	0.1	not detected
Breast	tissue	0.1	not detected
Prefrontal cortex	tissue	0.1
Retina	tissue	0.1
Pons	tissue	0.1
Smooth muscle	tissue	0.1	not detected
Colon	tissue	0.1	not detected
Motor cortex	tissue	0.1
Amygdala	tissue	0.1
Midbrain	tissue	0.1
Thalamus	tissue	0.1
Placenta	tissue	0.1	not detected
Thyroid gland	tissue	0.1	not detected
Duodenum	tissue	0.1	not detected
Spinal cord	tissue	0.1
Prostate	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Caudate nucleus (0.7), Reticular pontine nucleus, oral (0.7), Precentral gyrus (0.6), Blood vessel (0.5), Cervical spinal cord, central gray (0.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREM, SREBF2, YY1

Functional genomics

gnomAD constraint: pLI 0.000309, LOEUF 0.943, missense Z 1.29 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000216139 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
22:50,738,236–50,744,770	314 / 372.0	0.84	no
22:50,744,771–50,744,896	29 / 59.4	0.49	no
22:50,744,897–50,745,204	92 / 87.8	1.05	no

Literature-anchored findings (GeneRIF, showing 19)

• a constitutively active arrestin mutant can both induce agonist-independent internalization and stabilize the agonist-high affinity state of an arrestin-insensitive G protein coupled receptor. (PMID:12695524)
• news: beta-arrestin is now identified as a regulator of ubiquination and degradation of the Notch receptor (PMID:16319967)
• data suggest a novel model of arrestin-2 regulation mediated by inositol hexakisphosphate (PMID:16439357)
• Data show that the endocytic adapter protein AP-2 is essential for rhodopsin endocytosis through an arrestin2-AP-2beta interaction. (PMID:16835270)
• CaMKII is involved in the negative regulation of the visual response affecting light adaptation, possibly by catalyzing phosphorylation of Arr2 (PMID:19254957)
• We developed a steady-state stochastic model to interpret the dependence of the PDA on effective light intensity and arrestin content and to help deduce the arrestin to rhodopsin ratio from the sensitivity and PDA data. (PMID:19924417)
• Findings demonstrate that light-induced translocation of Arr2 occurs through a noncanonical rhodopsin/Rac2 pathway, which is distinct from the classical phototransduction cascade. (PMID:20176938)
• This study indicated that Arr2 translocation in Drosophila photoreceptors is driven by diffusion, but profoundly accelerated by phototransduction and Ca2+ influx. (PMID:20869596)
• Rapid calcium/calmodulin-dependent release of arrestin (Arr)2 from NINAC upon Ca2+ influx accounts for the acceleration of translocation by phototransduction. (PMID:22764229)
• identify a previously uncharacterized enzyme of ecdysone biosynthesis, GstE14, and find that ecdysone triggers pri expression to define the onset of epidermal trichome development (PMID:25344753)
• The pleiotropic functions of Pri smORF peptides synchronize leg development regulators. (PMID:37903161)
• crystal structure of an inactive T4 endo VII(N62D) complexed with an immobile four-way junction with alternating arm lengths of 10 and 14 base pairs (PMID:17873859)
• endo VII is the enzyme that recognizes mismatches in recombinational heteroduplexes and performs their incision (PMID:21237725)
• Binding sites for recombinant human zona pellucida (ZP) glycoproteins located at the N- and C-termini of proacrosin reveal a key role of the proenzyme in the interaction. (PMID:15950651)
• DNA immunization against proacrosin impairs fertility in male mice. (PMID:22452365)
• Sperm DNA damage is closely related with sperm-nucleoprotein transition, acrosin activity and seminal parameters. (PMID:23297503)
• Data indicate that the positive expression of studied genes fertilization rate for GAPDHS positive subset was 66%, ACR - 71%, SPATA22 - 68%, MND1 - 70%, pregnancy rates were 8%, 6%, 18% and 36% respectively. (PMID:23675907)
• Study revealed significantly higher acrosin activity and a lower DNA fragmentation index in subjects with moderate or high mitochondrial membrane potential (MMP) compared to those with low MMP. (PMID:30428044)
• Low acrosin activity is associated with decreased Spam1/acrosin expression and GSH deficiency-caused premature acrosome release of human sperm cells. (PMID:37833433)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Acr	ENSMUSG00000022622
rattus_norvegicus	Acr	ENSRNOG00000029762

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87884) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
delayed fertilization	2

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R5E8	99.3%	Diamond
Glossina austeni	Q4TTV7	98.2%	Diamond
Glossina fuscipes fuscipes	Q8MUG0	98.2%	Diamond
Manduca sexta	P35046	96.1%	Diamond
Capra hircus	P10626	90.0%	Diamond
Canis lupus familiaris	Q867B0	89.9%	Diamond
Sus scrofa	P08419	85.9%	Diamond
Bos taurus	Q29461	85.9%	Diamond
Streptomyces exfoliatus	P80420	82.7%	Diamond
Streptomyces griseus	P00775	81.1%	Diamond
Oryctolagus cuniculus	P48038	76.7%	Diamond
Ovis aries	Q9GL10	76.5%	Diamond
Streptomyces glaucescens	Q54179	71.3%	Diamond
Salmo salar	Q7SIG3	70.9%	Diamond
Bombus pensylvanicus	Q7M4I3	67.2%	Diamond
Drosophila melanogaster	Q9VWU1	66.9%	Diamond
Olivierus martensii	P0C8M2	59.5%	Diamond
Agelenopsis aperta	Q9TXD8	58.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SHANK3	protein-coding	85358
ARSA	protein-coding	410
RABL2B	protein-coding	11158

Protein

Protein identifiers

Acrosin — P10323 (reviewed: P10323)

All UniProt accessions (2): E9PLV5, P10323

UniProt curated annotations — full annotation on UniProt →

Function. Acrosin is the major protease of mammalian spermatozoa. It is a serine protease of trypsin-like cleavage specificity, it is synthesized in a zymogen form, proacrosin and stored in the acrosome.

Subunit / interactions. Heavy chain (catalytic) and a light chain linked by two disulfide bonds. Forms a heterodimer with SERPINA5.

Disease relevance. Spermatogenic failure 87 (SPGF87) [MIM:620500] An autosomal recessive male infertility disorder characterized by inability of mutant sperm to penetrate the zona pellucida, resulting in fertilization failure. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by SERPINA5.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_001088* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR012267	Pept_S1A_acrosin	Family
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504

Pfam: PF00089

Enzyme classification (BRENDA)

• EC 3.4.21.10 — acrosin (BRENDA: 49 organisms, 36 substrates, 243 inhibitors, 9 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
AMINOBENZOYL-SER-LYS-GLY-ARG-SER-LEU-ILE-GLY-LYS	0.022	1
NALPHA-BENZOYL-DL-LYSINE P-NITROANILIDE	0.65	1
NALPHA-BENZOYL-L-ARGININE 2-NAPHTHYLAMIDE	2.7	1
NALPHA-BENZOYL-L-ARGININE ETHYL ESTER	0.44	1
NALPHA-BENZOYL-L-ARGININE ETHYL ESTER HYDROCHLOR	0.28	1
NALPHA-BENZOYL-L-ARGININE P-NITROANILIDE	1.1	1
NALPHA-TOSYL-L-ARGININE METHYL ESTER	0.77	1
TOLUENE-P-SULFONYL-L-ARGININE METHYL ESTER	0.021	1
METHYL N2-[(4-METHYLPHENYL)SULFONYL]-L-ARGININAT	—	0

UniProt features (32 total): disulfide bond 6, sequence conflict 5, compositionally biased region 4, chain 3, active site 3, sequence variant 3, region of interest 3, glycosylation site 2, signal peptide 1, propeptide 1, domain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10323-F1	80.10	0.53

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted secreted proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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 (3)

Position	Role
88	charge relay system
142	charge relay system
240	charge relay system

Disulfide bonds (6)

Type	Positions
Interchain (between light and heavy chains)	25–154, 29–162
Disulfide bond	73–89, 177–246, 209–225, 236–266

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	22, 210

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-1300645	Acrosome Reaction and Sperm:Oocyte Membrane Binding	curated
R-HSA-1187000	Fertilization	—
R-HSA-1474165	Reproduction	—

MSigDB gene sets: 129 (showing top): GOBP_SINGLE_FERTILIZATION, MODULE_52, GOCC_SECRETORY_GRANULE, MODULE_45, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_LYASE_ACTIVITY, TGACCTY_ERR1_Q2, MODULE_16, GGGTGGRR_PAX4_03, MODULE_118, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_ADENYLATE_CYCLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, TGCTGAY_UNKNOWN, GOBP_SPERM_EGG_RECOGNITION

GO Biological Process (8): acrosome matrix dispersal (GO:0002077), activation of adenylate cyclase activity (GO:0007190), single fertilization (GO:0007338), acrosome reaction (GO:0007340), penetration of zona pellucida (GO:0007341), response to steroid hormone (GO:0048545), proteolysis (GO:0006508), protein catabolic process (GO:0030163)

GO Molecular Function (12): protease binding (GO:0002020), DNA binding (GO:0003677), amidase activity (GO:0004040), serine-type endopeptidase activity (GO:0004252), copper ion binding (GO:0005507), D-mannose binding (GO:0005537), serine-type peptidase activity (GO:0008236), zinc ion binding (GO:0008270), fucose binding (GO:0042806), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (6): extracellular region (GO:0005576), nucleus (GO:0005634), Golgi-associated vesicle (GO:0005798), protein-containing complex (GO:0032991), acrosomal matrix (GO:0043159), acrosomal vesicle (GO:0001669)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Fertilization	1
Reproduction	1

GO top-level categories

34 GO namespaces:

Category	Terms
single fertilization	2
protein metabolic process	2
transition metal ion binding	2
monosaccharide binding	2
cellular anatomical structure	2
acrosome reaction	1
protein catabolic process	1
positive regulation of adenylate cyclase activity	1
fertilization	1
membrane fusion involved in acrosome reaction	1
reproductive process	1
acrosomal vesicle exocytosis	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
response to hormone	1
response to lipid	1
macromolecule catabolic process	1
enzyme binding	1
nucleic acid binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasmic vesicle	1
cellular_component	1
acrosomal vesicle	1
vacuole	1
secretory granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
acrosome reaction	BP	mutant phenotype
activation of adenylate cyclase activity	BP	direct assay
nucleus	CC	high-throughput assay
protein-containing complex	CC	direct assay
D-mannose binding	MF	direct assay
serine-type endopeptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,218 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACR	SPATA16	Q9BXB7	696
ACR	ACRBP	Q8NEB7	691
ACR	TNP1	P09430	684
ACR	BOLL	Q8N9W6	656
ACR	CREM	Q03060	596
ACR	IZUMO1	Q8IYV9	589
ACR	SYCP3	Q8IZU3	572
ACR	SPA17	Q15506	555
ACR	ZAN	Q9Y493	551
ACR	ADGRA3	Q8IWK6	549
ACR	RIC3	Q7Z5B4	542
ACR	D6RI10	D6RI10	539
ACR	DAZL	Q92904	536
ACR	ZP3	P21754	526
ACR	STRA8	Q7Z7C7	524

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
ZP2	direct interaction	0.440	4
ZP3	direct interaction	0.440	2
ZP4	direct interaction	0.440	2

BioGRID (7 interactions; top human partners by supporting records): TP53BP1 (Two-hybrid; 2 records), GSK3A (Affinity Capture-MS), GSK3B (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), PTP4A3 (Positive Genetic), SERPINA5 (Reconstituted Complex)

Disease & clinical

Genetic variants

Variant evidence for ACR: 199 ClinVar records (103 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	103
Likely pathogenic	0
Uncertain significance	79
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 103 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
57193	GRCh38/hg38 22q13.31-13.33(chr22:47705262-50739836)x1	Pathogenic	criteria provided, multiple submitters, no conflicts	2
57264	GRCh38/hg38 22q13.31-13.33(chr22:45239376-50739836)x1	Pathogenic	criteria provided, single submitter	1
57672	GRCh38/hg38 22q13.31-13.33(chr22:44740175-50739836)x1	Pathogenic	criteria provided, single submitter	1
57673	GRCh38/hg38 22q13.31-13.33(chr22:45648256-50739836)x1	Pathogenic	criteria provided, single submitter	1
57674	GRCh38/hg38 22q13.31-13.33(chr22:47122613-50739836)x1	Pathogenic	criteria provided, single submitter	1
57675	GRCh38/hg38 22q13.31-13.33(chr22:47234701-50739836)x1	Pathogenic	criteria provided, single submitter	1
57701	GRCh38/hg38 22q13.32-13.33(chr22:48138038-50739836)x1	Pathogenic	criteria provided, single submitter	1
57704	GRCh38/hg38 22q13.33(chr22:49395349-50738932)x1	Pathogenic	criteria provided, single submitter	1
57947	GRCh38/hg38 22q13.31-13.33(chr22:44811200-50739836)x3	Pathogenic	criteria provided, single submitter	1
160852	GRCh38/hg38 22q13.33(chr22:50685063-50739836)x1	Pathogenic	criteria provided, single submitter	1
161055	GRCh38/hg38 22q13.33(chr22:50658268-50739836)x1	Pathogenic	criteria provided, single submitter	1
253555	GRCh37/hg19 22q13.33(chr22:50922386-51205985)x1	Pathogenic	criteria provided, single submitter	1
564973	GRCh37/hg19 22q13.33(chr22:51121452-51183840)x1	Pathogenic	criteria provided, single submitter	1
565012	GRCh37/hg19 22q13.33(chr22:50190425-51183767)x1	Pathogenic	criteria provided, single submitter	1
565013	GRCh37/hg19 22q13.33(chr22:50134203-51183840)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ACR’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 331):

Position(s)	Effect	Δscore	Sites
22:50739831	donor_gain	1.0000
22:50744207–50744208	donor_loss	0.9900	6
22:50740531	donor_gain	0.9800
22:50744059–50744060	acceptor_loss	0.9800	5
22:50744059	acceptor_loss	0.9700
22:50738313–50738314	donor_loss	0.9600	4
22:50739692–50739693	acceptor_loss	0.9600	5
22:50739915	donor_gain	0.9600
22:50744455	donor_gain	0.9600
22:50738313	donor_loss	0.9500

AlphaMissense

733 missense substitutions predicted likely pathogenic (of 2,697 scored), across 179 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D234	8	0.985	0.994
D239	8	0.983	0.994
D142	8	0.981	0.995
H88	8	0.943	0.966
S261	8	0.932	0.994
S240	8	0.931	0.979
S59	8	0.907	0.995
F90	8	0.877	0.977
H71	8	0.875	0.955
C209	7	0.997	0.999
C236	7	0.997	0.999
C266	7	0.996	0.999
C225	7	0.995	0.998
C89	7	0.993	0.996
W182	7	0.991	0.999
C73	7	0.986	0.995
C177	7	0.985	0.994
W284	7	0.984	0.999
C162	7	0.975	0.987
C246	7	0.968	0.991

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:102480 | disease phenotypes: MIM:620500, MIM:606232

GenCC curated gene-disease

Mondo (4): epilepsy (MONDO:0005027), autism spectrum disorder (MONDO:0005258), spermatogenic failure 87 (MONDO:0957594), Phelan-McDermid syndrome (MONDO:0011652)

Orphanet (2): Phelan-McDermid syndrome (Orphanet:48652), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

4 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:6000501	Ruffled acrosome

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
C536801	Telomeric 22q13 Monosomy Syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2738 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 9 [PMID: 3514912]	Inhibition	8.48	pIC50

Binding affinities (BindingDB)

162 measured of 164 human assays (164 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3287446	IC50	1400 nM
CHEMBL3287445	IC50	2300 nM
CHEMBL3287450	IC50	5700 nM
CHEMBL3287455	IC50	6400 nM
CHEMBL3287459	IC50	6600 nM
CHEMBL3287448	IC50	7800 nM
CHEMBL3287458	IC50	8400 nM
CHEMBL3287447	IC50	9300 nM
CHEMBL3287462	IC50	9400 nM
CHEMBL2397955	IC50	10000 nM
CHEMBL3287449	IC50	10100 nM
CHEMBL3287464	IC50	11500 nM
CHEMBL3287452	IC50	12100 nM
CHEMBL3287453	IC50	14400 nM
CHEMBL3287454	IC50	14400 nM
CHEMBL3287456	IC50	20300 nM
CHEMBL3287465	IC50	20500 nM
CHEMBL3287444	IC50	21400 nM
CHEMBL3287463	IC50	23900 nM
CHEMBL3287443	IC50	24600 nM
CHEMBL3287451	IC50	25400 nM
CHEMBL3287457	IC50	26800 nM
CHEMBL1911252	IC50	27000 nM
CHEMBL3287460	IC50	27900 nM
CHEMBL3287461	IC50	29900 nM
CHEMBL1834511	IC50	32000 nM
CHEMBL3287437	IC50	60000 nM
CHEMBL2397954	IC50	60000 nM
CHEMBL2023317	IC50	63000 nM
CHEMBL2316070	IC50	80000 nM
CHEMBL2397958	IC50	90000 nM
CHEMBL1834501	IC50	110000 nM
CHEMBL1911232	IC50	130000 nM
CHEMBL3287438	IC50	140000 nM
CHEMBL1911231	IC50	210000 nM
CHEMBL3287439	IC50	240000 nM
CHEMBL2316076	IC50	280000 nM
CHEMBL2022136	IC50	310000 nM
CHEMBL2397948	IC50	330000 nM
CHEMBL2316073	IC50	340000 nM
CHEMBL3287440	IC50	380000 nM
CHEMBL2397947	IC50	380000 nM
CHEMBL2316083	IC50	410000 nM
CHEMBL1834503	IC50	440000 nM
CHEMBL3287436	IC50	460000 nM
CHEMBL1834509	IC50	470000 nM
CHEMBL2023314	IC50	470000 nM
CHEMBL2397945	IC50	530000 nM
CHEMBL2316081	IC50	540000 nM
CHEMBL2397953	IC50	540000 nM

ChEMBL bioactivities

47 potent at pChembl≥5 of 82 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.17	IC50	0.67	nM	CHEMBL554140
8.92	IC50	1.2	nM	CHEMBL151747
8.52	IC50	3	nM	CHEMBL357455
8.48	IC50	3.3	nM	CHEMBL151454
8.46	IC50	3.5	nM	CHEMBL358868
8.27	IC50	5.4	nM	CHEMBL542258
8.25	IC50	5.6	nM	CHEMBL149324
8.18	IC50	6.6	nM	CHEMBL149135
8.14	IC50	7.2	nM	CHEMBL542261
8.10	IC50	8	nM	CHEMBL539058
8.03	IC50	9.3	nM	CHEMBL540096
7.94	IC50	11.4	nM	CHEMBL147344
7.89	IC50	12.9	nM	CHEMBL148957
7.86	IC50	13.7	nM	CHEMBL149157
7.79	IC50	16.3	nM	CHEMBL148731
7.75	IC50	17.6	nM	CHEMBL357708
7.70	IC50	19.8	nM	CHEMBL543454
7.56	IC50	27.3	nM	CHEMBL148833
7.54	IC50	28.5	nM	CHEMBL146905
7.48	IC50	33	nM	CHEMBL356950
7.42	IC50	38.5	nM	CHEMBL150009
7.00	IC50	99.7	nM	CHEMBL440176
6.52	IC50	300	nM	CHEMBL545564
6.52	IC50	300	nM	CHEMBL149156
5.90	IC50	1260	nM	CHEMBL3596546
5.85	IC50	1400	nM	CHEMBL3287446
5.64	IC50	2300	nM	CHEMBL3287445
5.62	IC50	2380	nM	CHEMBL3596545
5.62	IC50	2420	nM	CHEMBL3596567
5.62	IC50	2410	nM	CHEMBL1195245
5.46	IC50	3440	nM	CHEMBL3596564
5.37	IC50	4320	nM	CHEMBL3596563
5.24	IC50	5700	nM	CHEMBL3287450
5.24	IC50	5730	nM	CHEMBL3596551
5.23	IC50	5870	nM	CHEMBL3596562
5.19	IC50	6400	nM	CHEMBL3287455
5.18	IC50	6600	nM	CHEMBL3287459
5.13	IC50	7470	nM	CHEMBL3596558
5.11	IC50	7800	nM	CHEMBL3287448
5.08	IC50	8400	nM	CHEMBL3287458
5.07	IC50	8450	nM	CHEMBL3596556
5.03	IC50	9300	nM	CHEMBL3287447
5.03	IC50	9400	nM	CHEMBL3287462
5.03	IC50	9430	nM	CHEMBL3596547
5.02	IC50	9460	nM	CHEMBL3596554
5.00	IC50	1e+04	nM	CHEMBL2397955
5.00	IC50	1.01e+04	nM	CHEMBL3287449

PubChem BioAssay actives

34 with measured affinity, of 248 total; 34 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-methoxycarbonylphenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0007	uM
(4-cyanophenyl) 4-(diaminomethylideneamino)benzoate;4-methylbenzenesulfonic acid	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0012	uM
(4-chlorophenyl) 4-(diaminomethylideneamino)benzoate;4-methylbenzenesulfonic acid	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0030	uM
(4-methylphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0033	uM
(4-bromophenyl) 4-(diaminomethylideneamino)benzoate;4-methylbenzenesulfonic acid	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0035	uM
methyl 3-[4-(diaminomethylideneamino)benzoyl]oxybenzoate;hydrochloride	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0054	uM
phenyl 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0056	uM
(4-propan-2-ylphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0066	uM
(3-cyanophenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0072	uM
(4-acetamidophenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0080	uM
(4-ethoxycarbonylphenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0093	uM
(4-butoxyphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0114	uM
methyl 2-[4-(diaminomethylideneamino)benzoyl]oxybenzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0129	uM
(2-methoxy-4-prop-2-enylphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0137	uM
(4-methoxyphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0163	uM
(3-methoxyphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0176	uM
quinolin-8-yl 4-(diaminomethylideneamino)benzoate;hydrochloride	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0198	uM
(2-methoxyphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0273	uM
(4-tert-butylphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0285	uM
[4-(trifluoromethyl)phenyl] 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0330	uM
[3-(trifluoromethyl)phenyl] 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0385	uM
(4-hexyl-3-hydroxyphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.0997	uM
(2-carbamoylphenyl) 4-(diaminomethylideneamino)benzoate;hydrochloride	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.3000	uM
4-methylbenzenesulfonic acid;(5-methyl-2-propan-2-ylphenyl) 4-(diaminomethylideneamino)benzoate	30425: Inhibition of human acrosin and control activity being 11.3 umol/min/mg	ic50	0.3000	uM
5-[4-(diaminomethylideneamino)phenyl]-N-(2,4-dimethoxyphenyl)-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	1.4000	uM
5-[4-(diaminomethylideneamino)phenyl]-N-(2,5-dimethoxyphenyl)-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	2.3000	uM
5-[4-(diaminomethylideneamino)phenyl]-N-(2,6-dimethylphenyl)-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	5.7000	uM
5-[4-(diaminomethylideneamino)phenyl]-N-(4-ethoxyphenyl)-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	6.4000	uM
5-[4-(diaminomethylideneamino)phenyl]-N-(3-methoxyphenyl)-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	6.6000	uM
N-(4-tert-butylphenyl)-5-[4-(diaminomethylideneamino)phenyl]-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	7.8000	uM
5-[4-(diaminomethylideneamino)phenyl]-N-(2-methoxyphenyl)-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	8.4000	uM
ethyl 4-[[5-[4-(diaminomethylideneamino)phenyl]-1,2-oxazole-3-carbonyl]amino]benzoate;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	9.3000	uM
5-[4-(diaminomethylideneamino)phenyl]-N-(3-methylphenyl)-1,2-oxazole-3-carboxamide;hydrochloride	1153329: Inhibition of human acrosin using N-alpha-benzoyl-L-arginine p-nitroanilide as substrate after 3 hrs by spectrophotometry	ic50	9.4000	uM
N,N-bis(2-hydroxypropyl)-3-phenyl-1H-pyrazole-5-carboxamide	756546: Inhibition of human sperm acrosin using BAPNA as substrate after 3 hrs by spectrophotometric analysis	ic50	10.0000	uM

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Testosterone	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

20 unique, capped per target: 18 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1839245	Binding	Inhibition of human acrosin using N-alpha-benzoyl-DL-arginine para-nitroanilide-HCl as substrate after 3 hrs by spectrophotometry	Synthesis and acrosin inhibitory activities of substituted ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives. — *Bioorg Med Chem Lett*
CHEMBL639048	Functional	Compound was evaluated for the reactivity in the inactivation of trypsin like boar acrosin	Inactivation of trypsin-like proteases by depsipeptides of p-guanidinobenzoic acid. — *J Med Chem*

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00211796	Phase 4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	Phase 4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	Phase 4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	Phase 4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	Phase 4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	Phase 4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	Phase 4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	Phase 4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT00036231	Phase 3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	Phase 3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	Phase 3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	Phase 3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	Phase 3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	Phase 3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	Phase 3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	Phase 3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	Phase 3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	Phase 3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	Phase 3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms
NCT00549562	Phase 3	COMPLETED	Study of Paliperidone ER in Adolescents and Young Adults With Autism
NCT00584480	Phase 3	COMPLETED	Pilot Study of the Effect of Hyperbaric Oxygen Treatment on Behavioral and Biomarker Measures in Children With Autism
NCT00655174	Phase 3	COMPLETED	Fluvoxamine and Sertraline in Childhood Autism - Does SSRI Therapy Improve Behaviour and/or Mood?
NCT00881452	Phase 3	COMPLETED	A Trial of CM-AT in Children With Autism
NCT00912691	Phase 3	COMPLETED	A Trial of CM-AT in Children With Autism- Open Label Extension Study
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01740869	Phase 3	COMPLETED	Autologous Bone Marrow Stem Cells for Children With Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01911442	Phase 3	COMPLETED	Lurasidone Pediatric Autism Study
NCT01914393	Phase 3	COMPLETED	Pediatric Open-Label Extension Study
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02410902	Phase 3	COMPLETED	A Trial of CM-AT in Children With Autism With All Levels of FCT (The Blum Study)
NCT02649959	Phase 3	ACTIVE_NOT_RECRUITING	An Open Label Study of CM-AT for the Treatment of Children With Autism
NCT02654743	Phase 3	COMPLETED	Open Label of Clinical Trial of Sulforaphane in Children With Autism
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACR across ~30M SureChEMBL compounds — explore on Sugi Predict.