DPYSL3

Summary

DPYSL3 (dihydropyrimidinase like 3, HGNC:3015) is a protein-coding gene on chromosome 5q32, encoding Dihydropyrimidinase-related protein 3 (Q14195). Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton.

Enables filamin binding activity. Predicted to be involved in several processes, including actin filament organization; regulation of plasma membrane bounded cell projection organization; and response to axon injury. Predicted to act upstream of or within nervous system development. Predicted to be located in several cellular components, including exocytic vesicle; growth cone; and lamellipodium. Predicted to be part of filamentous actin. Predicted to be active in cytosol and synapse.

Source: NCBI Gene 1809 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 82 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_001197294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3015
Approved symbol	DPYSL3
Name	dihydropyrimidinase like 3
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	DRP-3, ULIP, CRMP4
Ensembl gene	ENSG00000113657
Ensembl biotype	protein_coding
OMIM	601168
Entrez	1809

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000343218, ENST00000398514, ENST00000504965, ENST00000507309, ENST00000508042, ENST00000512722, ENST00000519672, ENST00000520473, ENST00000523458, ENST00000891850, ENST00000938658, ENST00000938659

RefSeq mRNA: 2 — MANE Select: NM_001197294 NM_001197294, NM_001387

CCDS: CCDS43381, CCDS56387

Canonical transcript exons

ENST00000343218 — 14 exons

Exon	Start	End
ENSE00000766839	147395559	147395721
ENSE00000766842	147400692	147400833
ENSE00000875419	147418447	147418631
ENSE00001388244	147415709	147415873
ENSE00001475588	147509478	147510068
ENSE00001758493	147405610	147405730
ENSE00002065061	147390808	147394123
ENSE00003480555	147401540	147401696
ENSE00003542259	147399082	147399252
ENSE00003585367	147397666	147397845
ENSE00003597594	147412608	147412688
ENSE00003598682	147408728	147408796
ENSE00003626816	147413596	147413657
ENSE00003638301	147424875	147424963

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.2998 / max 1389.1310, expressed in 1401 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64035	15.5166	1097
64043	10.3658	1209
64046	6.4983	967
64038	2.9053	782
64048	2.4767	912
64044	1.0273	620
64036	1.0063	427
64039	0.8289	355
64040	0.6388	327
64034	0.6290	349

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.71	gold quality
ganglionic eminence	UBERON:0004023	99.49	gold quality
ventricular zone	UBERON:0003053	99.15	gold quality
saphenous vein	UBERON:0007318	99.00	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.85	gold quality
lower esophagus	UBERON:0013473	98.79	gold quality
mucosa of stomach	UBERON:0001199	98.33	gold quality
cauda epididymis	UBERON:0004360	98.25	gold quality
right coronary artery	UBERON:0001625	98.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.10	gold quality
popliteal artery	UBERON:0002250	98.09	gold quality
tibial artery	UBERON:0007610	98.09	gold quality
aorta	UBERON:0000947	98.07	gold quality
ascending aorta	UBERON:0001496	98.07	gold quality
thoracic aorta	UBERON:0001515	98.06	gold quality
urethra	UBERON:0000057	97.95	gold quality
cranial nerve II	UBERON:0000941	97.93	gold quality
smooth muscle tissue	UBERON:0001135	97.91	gold quality
descending thoracic aorta	UBERON:0002345	97.82	gold quality
dorsal root ganglion	UBERON:0000044	97.66	gold quality
myometrium	UBERON:0001296	97.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.38	gold quality
blood vessel layer	UBERON:0004797	97.35	gold quality
body of uterus	UBERON:0009853	97.25	gold quality
gall bladder	UBERON:0002110	97.24	gold quality
right ovary	UBERON:0002118	97.23	gold quality
left uterine tube	UBERON:0001303	97.22	gold quality
calcaneal tendon	UBERON:0003701	97.11	gold quality
left ovary	UBERON:0002119	97.01	gold quality
synovial joint	UBERON:0002217	96.93	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-CURD-10	yes	264.60
E-GEOD-100618	yes	236.51
E-GEOD-135922	yes	52.63
E-HCAD-5	yes	17.54
E-MTAB-5061	yes	14.09
E-ANND-3	yes	12.53
E-CURD-114	yes	11.92
E-GEOD-81608	yes	8.86
E-ENAD-27	yes	4.52
E-GEOD-81547	yes	4.46
E-GEOD-137537	yes	4.05
E-MTAB-11121	no	1029.35
E-ENAD-20	no	128.80
E-GEOD-83139	no	3.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

105 targeting DPYSL3, 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-3120-5P	100.00	65.56	965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4755-5P	99.71	70.34	2716

Literature-anchored findings (GeneRIF, showing 22)

• Aberrant expression of dihydropyrimidinase related proteins-2,-3 and -4 in fetal Down syndrome brain. (PMID:11771764)
• HUlip was expressed in late fetal and early postnatal brains in the neurons of the brain stem, basal ganglia/thalamus, and dentate gyrus of the hippocampus. HUlip expression was easily detected in tumor cells undergoing neuronal differentiation. [Ulip] (PMID:15933812)
• GSK3 alters phosphorylation of CRMP-1, -2, and -4 isoforms (PMID:16611631)
• new function of CRMP4 as a metastasis-suppressor in lymph node metastasis of prostate cancer (PMID:20543870)
• Data show that two genes, LTB4DH and DPYSL3, were confirmed to be candidate genes for the predictor of a good immune response. (PMID:20804502)
• Ulip1 was downregulated and HIF1a was upregulated in hypoxic neuroblastoma cells. (PMID:20977846)
• CRMP4 is a key physiological substrate of GSK3 in regulating chromosomal alignment and mitotic progression through its effect on spindle microtubules (PMID:21179545)
• High collapsin response mediator protein 4 expression is associated with liver metastasis in pancreatic cancer. (PMID:22805864)
• study found the association between the rs147541241 variant and amyotrophic lateral scerosis was limited to the French population (PMID:23568759)
• Downregulation of MYCN by small interfering RNA (siRNA) increased DPYSL3 levels, while upregulation of MYCN in non-MYCN NB cells decreased DPYSL3 levels. (PMID:24011394)
• DPYSL3 as pancreatic ductal adenocarcinoma-associated molecule that regulates cell adhesion and migration by stabilization of focal adhesion complex (PMID:24339867)
• structures provide further insight into the effects of medically relevant mutations of the DPYSL-3 gene encoding CRMP-4 and the putative enzymatic activities of CRMPs (PMID:24914979)
• Expression status of DPYSL3 in gastric cancer tissues may represent a promising biomarker for the malignant behavior of GC. (PMID:25096402)
• DPYSL3 expression levels inversely correlated with those of VEGF and FAK. Down-regulation of DPYSL3 expression in HCC tissues may serve as a predictive biomarker for HCC after curative resection. (PMID:25173447)
• Data indicate that CRMP4a and CRMP4b isoforms have opposite effects on cell proliferation, migration, and invasion in gastric cancer. CRMP4a expression was reduced in gastric carcinoma tissues and cell lines and seems to act as a tumor suppressor in gastric carcinoma. CRMP4b expression was higher in tumor tissue and cell lines. (PMID:27475326)
• CRMP4 methylation levels >/=15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis (PMID:28382925)
• Data found a damaging de novo missense CRMP4 mutation in a male autism spectrum disorders (ASD). Accumulating evidence suggests that a disturbance in the regulatory function of CRMP4 in forming neuronal networks is an important aspect underlying some characteristics of ASD, including sexual differences. These findings provide CRMP4 as a novel candidate gene contributing to ASD. (PMID:29196732)
• DPYSL3 expression identifies claudin-low (CLOW) tumors that will be sensitive to approaches that promote vimentin phosphorylation during mitosis and inhibitors of PAK signaling during migration and EMT. (PMID:30498031)
• Diabetes, an independent poor prognostic factor of non-B non-C hepatocellular carcinoma, correlates with dihydropyrimidinase-like 3 promoter methylation. (PMID:31980687)
• Upregulation of Thr/Tyr kinase Increases the Cancer Progression by Neurotensin and Dihydropyrimidinase-Like 3 in Lung Cancer. (PMID:32121246)
• Collapsin response mediator protein 4 enhances the radiosensitivity of colon cancer cells through calciummediated cell signaling. (PMID:33655336)
• Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma. (PMID:37380971)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpysl3	ENSDARG00000002587
mus_musculus	Dpysl3	ENSMUSG00000024501
rattus_norvegicus	Dpysl3	ENSRNOG00000018992

Paralogs (5): CRMP1 (ENSG00000072832), DPYSL2 (ENSG00000092964), DPYS (ENSG00000147647), DPYSL4 (ENSG00000151640), DPYSL5 (ENSG00000157851)

Protein

Protein identifiers

Dihydropyrimidinase-related protein 3 — Q14195 (reviewed: Q14195)

Alternative names: Collapsin response mediator protein 4, Unc-33-like phosphoprotein 1

All UniProt accessions (5): A0A140VK07, D6RF19, Q14195, H0YB87, H0YBT4

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration.

Subunit / interactions. Homotetramer, and heterotetramer with CRMP1, DPYSL2, DPYSL4 or DPYSL5. Interacts with synaptic vesicle protein 2 and SH3A domain of intersectin. Interacts with FLNA.

Subcellular location. Cytoplasm. Cell projection. Growth cone.

Tissue specificity. Mainly expressed in heart and skeletal muscle. Also strongly expressed in fetal brain and spinal cord.

Post-translational modifications. Phosphorylation on Ser-522 by DYRK2 promotes subsequent phosphorylation on Thr-509, Thr-514 and Ser-518 by GSK3.

Similarity. Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14195-1	1	yes
Q14195-2	LCRMP-4

RefSeq proteins (2): NP_001184223, NP_001378 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006680	Amidohydro-rel	Domain
IPR011059	Metal-dep_hydrolase_composite	Homologous_superfamily
IPR011778	Hydantoinase/dihydroPyrase	Family
IPR032466	Metal_Hydrolase	Homologous_superfamily
IPR050378	Metallo-dep_Hydrolases_sf	Family

Pfam: PF01979

UniProt features (60 total): helix 19, strand 16, modified residue 12, turn 6, sequence conflict 2, chain 1, region of interest 1, splice variant 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4BKN	X-RAY DIFFRACTION	2.1
4CNS	X-RAY DIFFRACTION	2.4
4CNT	X-RAY DIFFRACTION	2.65
4CNU	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14195-F1	90.49	0.84

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 (12): 536, 539, 541, 543, 259, 431, 499, 102, 509, 514, 518, 522

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-399956	CRMPs in Sema3A signaling

MSigDB gene sets: 324 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MODULE_52, RRAGTTGT_UNKNOWN, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, JI_RESPONSE_TO_FSH_UP, GGTGTGT_MIR329, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_RESPONSE_TO_PEPTIDE, ATACCTC_MIR202, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS

GO Biological Process (10): positive regulation of neuron projection development (GO:0010976), negative regulation of neuron projection development (GO:0010977), negative regulation of cell migration (GO:0030336), neuron development (GO:0048666), response to axon injury (GO:0048678), actin filament bundle assembly (GO:0051017), positive regulation of filopodium assembly (GO:0051491), actin crosslink formation (GO:0051764), cellular response to cytokine stimulus (GO:0071345), nervous system development (GO:0007399)

GO Molecular Function (9): hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides (GO:0016812), SH3 domain binding (GO:0017124), filamin binding (GO:0031005), chondroitin sulfate binding (GO:0035374), identical protein binding (GO:0042802), phosphoprotein binding (GO:0051219), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds (GO:0016810)

GO Cellular Component (10): obsolete extracellular space (GO:0005615), cytosol (GO:0005829), lamellipodium (GO:0030027), growth cone (GO:0030426), filamentous actin (GO:0031941), cell body (GO:0044297), synapse (GO:0045202), exocytic vesicle (GO:0070382), cytoplasm (GO:0005737), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Semaphorin interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of neuron projection development	2
neuron projection development	2
protein binding	2
positive regulation of cell projection organization	1
negative regulation of cell projection organization	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
neuron differentiation	1
cell development	1
response to wounding	1
cellular component assembly	1
actin filament bundle organization	1
filopodium assembly	1
regulation of filopodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
actin filament organization	1
response to cytokine	1
system development	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
protein domain specific binding	1
cytoskeletal protein binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
catalytic activity	1
hydrolase activity	1
cytoplasm	1
cell leading edge	1
plasma membrane bounded cell projection	1
site of polarized growth	1
distal axon	1
actin filament	1
protein-containing complex	1
cell junction	1
transport vesicle	1
secretory vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPYSL3	RHOA	P06749	774
DPYSL3	SEMA3A	Q14563	690
DPYSL3	STK32A	Q8WU08	651
DPYSL3	PLXNA2	O75051	585
DPYSL3	PLXNA1	Q9UIW2	567
DPYSL3	GAP43	P17677	561
DPYSL3	DPYD	Q12882	519
DPYSL3	ITSN1	Q15811	481
DPYSL3	CDK5	Q00535	477
DPYSL3	SMIM24	O75264	464
DPYSL3	DBN1	Q16643	457
DPYSL3	EPDR1	Q9UM22	456
DPYSL3	ROBO1	Q9Y6N7	452
DPYSL3	DUS2	Q9NX74	443
DPYSL3	EZR	P15311	435

IntAct

82 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
DPYSL3	DPYSL2	psi-mi:“MI:0915”(physical association)	0.750
DPYSL2	DPYSL3	psi-mi:“MI:0915”(physical association)	0.750
DPYSL5	DPYSL4	psi-mi:“MI:0914”(association)	0.640
DPYSL3	DPYSL4	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
RWDD2A	ATG7	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
DPYS	DPYSL3	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
POLR2A	URI1	psi-mi:“MI:0914”(association)	0.530
RRP7A	ATP4A	psi-mi:“MI:0914”(association)	0.530
PRKAA1	MTIF2	psi-mi:“MI:0914”(association)	0.530
DPYSL4	PLCG1	psi-mi:“MI:0914”(association)	0.530
ACD	DPYSL3	psi-mi:“MI:0915”(physical association)	0.510
DPYSL3	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
C3orf49	DPYSL3	psi-mi:“MI:0915”(physical association)	0.400
TERF1	DPYSL3	psi-mi:“MI:0915”(physical association)	0.370
DPYSL3	POT1	psi-mi:“MI:0915”(physical association)	0.370
DPYSL3	DPYSL2	psi-mi:“MI:0915”(physical association)	0.370
Odf2	DPYSL3	psi-mi:“MI:0914”(association)	0.350
ORF73	ECI2	psi-mi:“MI:0914”(association)	0.350

BioGRID (127): DPYSL3 (Two-hybrid), DPYSL3 (Two-hybrid), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Proximity Label-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0F7GG06, A0A1I9LN01, B9FDB8, D4B2N2, D4DEJ7, F4JXC5, M1VV65, O08553, O13022, O14057, O14124, O14531, O35098, O50039, O81220, P14671, P32375, P34480, P47942, P97427, Q07729, Q0JJD1, Q10LR9, Q14117, Q14194, Q14195, Q2QMN7, Q2UPB0, Q52PJ5, Q5RAV9, Q62188, Q62950, Q62951, Q62952, Q63150, Q640K6, Q6GL72, Q6Q886, Q94AP0, Q9BPU6

Diamond homologs: A1AF64, A7ZQY1, A7ZXG5, A8A415, B1ITC8, B1IZ89, B1XEG2, B6I0G2, B6I707, B7L7D8, B7LF59, B7LYD8, B7M4L5, B7MM60, B7MZ27, B7N7B8, B7N966, B7NW14, B7UHS3, C5A0E6, O02675, O08553, O13022, O14531, O35098, O69809, P47942, P81006, P97427, Q02C42, Q0TDX8, Q14117, Q14194, Q14195, Q16555, Q18677, Q1AS71, Q1J391, Q1R7F8, Q21773

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
CDK5	“up-regulates activity”	DPYSL3	phosphorylation
DYRK2	“up-regulates activity”	DPYSL3	phosphorylation
GSK3B	“up-regulates activity”	DPYSL3	phosphorylation
GSK3B	“down-regulates activity”	DPYSL3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Signaling by Rho GTPases	9	4.8×	9e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	9	4.7×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
nervous system development	13	7.6×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2446 predictions. Top by Δscore:

Variant	Effect	Δscore
5:147397661:TTTAC:T	donor_loss	1.0000
5:147397662:TTAC:T	donor_loss	1.0000
5:147397663:TA:T	donor_loss	1.0000
5:147397664:ACCTT:A	donor_gain	1.0000
5:147397665:CCT:C	donor_loss	1.0000
5:147397665:CCTTC:C	donor_gain	1.0000
5:147397668:T:A	donor_gain	1.0000
5:147399080:A:AC	donor_gain	1.0000
5:147399081:C:CC	donor_gain	1.0000
5:147399081:CAGA:C	donor_gain	1.0000
5:147399084:A:AC	donor_gain	1.0000
5:147399085:C:CC	donor_gain	1.0000
5:147399248:GTGGC:G	acceptor_gain	1.0000
5:147399249:TGGC:T	acceptor_gain	1.0000
5:147399252:CCTA:C	acceptor_loss	1.0000
5:147399253:C:CC	acceptor_gain	1.0000
5:147400829:CCCCG:C	acceptor_gain	1.0000
5:147400830:CCCG:C	acceptor_gain	1.0000
5:147400830:CCCGC:C	acceptor_gain	1.0000
5:147400831:CCG:C	acceptor_gain	1.0000
5:147400831:CCGC:C	acceptor_gain	1.0000
5:147400832:CGC:C	acceptor_gain	1.0000
5:147400834:C:CC	acceptor_gain	1.0000
5:147401535:CCAA:C	donor_loss	1.0000
5:147401536:CAA:C	donor_loss	1.0000
5:147401537:AAC:A	donor_loss	1.0000
5:147401538:A:C	donor_loss	1.0000
5:147401539:C:CG	donor_loss	1.0000
5:147401693:TTTC:T	acceptor_gain	1.0000
5:147401694:TTC:T	acceptor_gain	1.0000

AlphaMissense

4521 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:147395569:A:C	F538L	0.999
5:147395569:A:T	F538L	0.999
5:147395571:A:G	F538L	0.999
5:147399129:A:G	W412R	0.999
5:147399129:A:T	W412R	0.999
5:147399167:C:T	G399E	0.999
5:147399168:C:G	G399R	0.999
5:147399168:C:T	G399R	0.999
5:147399197:G:T	A389D	0.999
5:147399208:G:C	S385R	0.999
5:147399208:G:T	S385R	0.999
5:147399210:T:G	S385R	0.999
5:147400809:A:C	S331R	0.999
5:147400809:A:T	S331R	0.999
5:147400811:T:G	S331R	0.999
5:147424878:A:T	I42K	0.999
5:147394066:C:T	G561D	0.998
5:147395695:C:A	R496S	0.998
5:147395695:C:G	R496S	0.998
5:147395696:C:A	R496M	0.998
5:147395702:A:T	V494D	0.998
5:147399137:A:G	L409P	0.998
5:147399161:A:T	I401K	0.998
5:147400706:A:G	W366R	0.998
5:147400706:A:T	W366R	0.998
5:147400720:C:G	R361P	0.998
5:147401612:G:T	A299D	0.998
5:147424929:A:T	V25D	0.998
5:147395570:A:G	F538S	0.997
5:147395696:C:G	R496T	0.997

dbSNP variants (sampled 300 via entrez): RS1000045998 (5:147445791 C>T), RS1000048506 (5:147429667 T>C), RS1000051878 (5:147482091 A>G), RS1000086614 (5:147460423 T>A), RS1000136532 (5:147479051 G>C), RS1000146291 (5:147451930 C>T), RS1000170394 (5:147404227 A>G), RS1000184252 (5:147422467 G>A), RS1000205679 (5:147424902 T>A,C), RS1000209444 (5:147478866 G>A,T), RS1000241616 (5:147470960 C>T), RS1000262300 (5:147442099 T>G), RS1000278993 (5:147398337 T>A), RS1000314142 (5:147441788 C>A,T), RS1000326926 (5:147458219 G>C,T)

Disease associations

OMIM: gene MIM:601168 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003979_5	Excessive daytime sleepiness	1.000000e-07
GCST009391_119	Metabolite levels	6.000000e-06
GCST009391_1560	Metabolite levels	8.000000e-06
GCST009391_473	Metabolite levels	6.000000e-06
GCST009391_603	Metabolite levels	5.000000e-06
GCST010702_118	Subcortical volume (MOSTest)	2.000000e-09
GCST010703_57	Brain morphology (MOSTest)	1.000000e-08
GCST012490_15	Femur bone mineral density x serum urate levels interaction	3.000000e-13

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007875	excessive daytime sleepiness measurement
EFO:0010354	diacylglycerol 36:1 measurement
EFO:0009776	ornithine measurement
EFO:0010505	isocitrate measurement
EFO:0004346	neuroimaging measurement
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067145 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.45	Kd	358.9	nM	CHEMBL3752910
6.42	ED50	378.9	nM	CHEMBL3752910
6.22	Kd	605.7	nM	CHEMBL5653589
6.19	ED50	639.3	nM	CHEMBL5653589

PubChem BioAssay actives

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

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148263: Binding affinity to human DPYSL3 incubated for 45 mins by Kinobead based pull down assay	kd	0.3589	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148263: Binding affinity to human DPYSL3 incubated for 45 mins by Kinobead based pull down assay	kd	0.6057	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression	7
Benzo(a)pyrene	increases expression, increases methylation, affects cotreatment, affects methylation	5
bisphenol A	decreases expression, increases expression	3
sodium arsenite	affects methylation, decreases expression, increases abundance	3
methylmercuric chloride	decreases expression	2
trichostatin A	decreases expression	2
(+)-JQ1 compound	increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Doxorubicin	affects expression, decreases expression	2
Hydrogen Peroxide	affects expression, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	increases expression, decreases expression	2
Aflatoxin B1	decreases methylation	2
GSK-J4	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
OTX015	increases expression	1
FR900359	decreases phosphorylation	1
mivebresib	increases expression	1
chloroacetaldehyde	affects expression	1
salinomycin	decreases expression	1
arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
cylindrospermopsin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
adefovir dipivoxil	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651305	Binding	Binding affinity to human DPYSL3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms