DPYSL4

Summary

DPYSL4 (dihydropyrimidinase like 4, HGNC:3016) is a protein-coding gene on chromosome 10q26.3, encoding Dihydropyrimidinase-related protein 4 (O14531). Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton.

Enables filamin binding activity. Predicted to be involved in nervous system development. Predicted to be located in cytoplasm. Predicted to be active in cytosol.

Source: NCBI Gene 10570 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 114 total — 2 pathogenic
• MANE Select transcript: NM_006426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3016
Approved symbol	DPYSL4
Name	dihydropyrimidinase like 4
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	ULIP4, DRP-4, CRMP3
Ensembl gene	ENSG00000151640
Ensembl biotype	protein_coding
OMIM	608407
Entrez	10570

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000338492, ENST00000368627, ENST00000471544, ENST00000493882, ENST00000493927, ENST00000905070, ENST00000905071, ENST00000905072, ENST00000905073, ENST00000930866, ENST00000949793

RefSeq mRNA: 1 — MANE Select: NM_006426 NM_006426

CCDS: CCDS7665

Canonical transcript exons

ENST00000338492 — 14 exons

Exon	Start	End
ENSE00001000772	132202646	132202825
ENSE00001000773	132198851	132198971
ENSE00001000775	132197021	132197101
ENSE00001000776	132198415	132198483
ENSE00001000777	132196861	132196922
ENSE00001000784	132200842	132200983
ENSE00001000785	132201946	132202116
ENSE00001153817	132203762	132203927
ENSE00001153842	132200356	132200512
ENSE00003323245	132204839	132205759
ENSE00003462525	132186948	132187102
ENSE00003522018	132194845	132195009
ENSE00003542602	132192658	132192842
ENSE00003580789	132190747	132190835

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1509 / max 108.1004, expressed in 1112 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107704	5.3039	1073
107703	0.8471	453

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.12	gold quality
ganglionic eminence	UBERON:0004023	96.20	gold quality
cortical plate	UBERON:0005343	94.08	gold quality
right frontal lobe	UBERON:0002810	93.33	gold quality
endothelial cell	CL:0000115	92.47	gold quality
prefrontal cortex	UBERON:0000451	90.95	gold quality
ventricular zone	UBERON:0003053	90.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.49	gold quality
cingulate cortex	UBERON:0003027	90.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.34	gold quality
anterior cingulate cortex	UBERON:0009835	90.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.15	gold quality
neocortex	UBERON:0001950	90.02	gold quality
frontal cortex	UBERON:0001870	89.84	gold quality
embryo	UBERON:0000922	89.79	gold quality
cerebral cortex	UBERON:0000956	89.45	gold quality
primary visual cortex	UBERON:0002436	89.15	gold quality
nucleus accumbens	UBERON:0001882	89.00	gold quality
heart left ventricle	UBERON:0002084	88.98	gold quality
caudate nucleus	UBERON:0001873	88.79	gold quality
middle temporal gyrus	UBERON:0002771	88.74	gold quality
amygdala	UBERON:0001876	88.55	gold quality
cardiac ventricle	UBERON:0002082	88.52	gold quality
telencephalon	UBERON:0001893	88.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.45	gold quality
Ammon’s horn	UBERON:0001954	88.39	gold quality
forebrain	UBERON:0001890	87.82	gold quality
spinal cord	UBERON:0002240	87.76	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.71	gold quality
putamen	UBERON:0001874	87.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting DPYSL4, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-342-5P	97.25	64.10	817
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-4509	96.19	65.80	900
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 4)

• Aberrant expression of dihydropyrimidinase related proteins-2,-3 and -4 in fetal Down syndrome brain. (PMID:11771764)
• DPYSL4 is a novel apoptosis-inducible factor controlled by p53 in response to DNA damage (PMID:20499313)
• DPYSL4 plays a key role in the tumor-suppressor function of p53 by regulating oxidative phosphorylation and the cellular energy supply via its association with mitochondrial supercomplexes, possibly linking to the pathophysiology of both cancer and obesity. (PMID:30061407)
• Identification of Metabolic Syndrome-Related miRNA-mRNA Regulatory Networks and Key Genes Based on Bioinformatics Analysis. (PMID:35877019)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dpysl4	ENSMUSG00000025478
rattus_norvegicus	Dpysl4	ENSRNOG00000027582

Paralogs (5): CRMP1 (ENSG00000072832), DPYSL2 (ENSG00000092964), DPYSL3 (ENSG00000113657), DPYS (ENSG00000147647), DPYSL5 (ENSG00000157851)

Protein

Protein identifiers

Dihydropyrimidinase-related protein 4 — O14531 (reviewed: O14531)

Alternative names: Collapsin response mediator protein 3, UNC33-like phosphoprotein 4

All UniProt accessions (2): O14531, Q5T0Q6

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, DPYSL3 or DPYSL5. Interacts with PLEXA1. Interacts with FLNA.

Subcellular location. Cytoplasm.

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

RefSeq proteins (1): NP_006417* (*=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 (47 total): helix 19, strand 18, turn 6, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5NKS	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14531-F1	90.45	0.83

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 (2): 537, 544

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-399956	CRMPs in Sema3A signaling

MSigDB gene sets: 116 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, PEREZ_TP63_TARGETS, MODULE_45, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, MODULE_66, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, GOBP_NUCLEOBASE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_88, PEREZ_TP53_AND_TP63_TARGETS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, LEF1_Q6, MODULE_11, MODULE_60

GO Biological Process (1): nervous system development (GO:0007399)

GO Molecular Function (5): hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides (GO:0016812), filamin binding (GO:0031005), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds (GO:0016810)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

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	2
system development	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
cytoskeletal protein binding	1
binding	1
catalytic activity	1
hydrolase activity	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPYSL4	SGSM1	Q2NKQ1	502
DPYSL4	INPP5A	Q14642	485
DPYSL4	CACNA1B	Q00975	474
DPYSL4	HSPBAP1	Q96EW2	448
DPYSL4	ARHGEF10L	Q9HCE6	434
DPYSL4	TCERG1L	Q5VWI1	426
DPYSL4	PHACTR3	Q96KR7	420
DPYSL4	DPYSL5	Q9BPU6	414
DPYSL4	GALNT5	Q7Z7M9	403
DPYSL4	NGF	P01138	385
DPYSL4	POLR1D	P0DPB6	383
DPYSL4	C1orf159	Q96HA4	370
DPYSL4	ATP6V1G2	O95670	364
DPYSL4	GART	P22102	353
DPYSL4	MACO1	Q8N5G2	347

IntAct

74 interactions, top by confidence:

A	B	Type	Score
DPYSL4	DPYSL2	psi-mi:“MI:0915”(physical association)	0.660
DPYSL5	DPYSL4	psi-mi:“MI:0914”(association)	0.640
DPYSL3	DPYSL4	psi-mi:“MI:0914”(association)	0.640
DPYSL4	TRIP13	psi-mi:“MI:0915”(physical association)	0.560
DPYSL4	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
TRIP13	DPYSL4	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	DPYSL4	psi-mi:“MI:0915”(physical association)	0.560
GRN	DPYSL4	psi-mi:“MI:0915”(physical association)	0.560
PRKACA	DPYSL4	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	DPYSL4	psi-mi:“MI:0915”(physical association)	0.560
DPYSL4	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DPYSL4	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
DPYSL4	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (77): DPYSL4 (Two-hybrid), RBPMS (Two-hybrid), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A2VDS1, A5GFY8, A5GFZ6, A6H791, A7MBC0, D4AAT7, E1BNQ4, E2QUI9, O14531, O35098, O43175, O75600, O95396, O95571, P13439, P31754, P38918, P43353, Q14117, Q16555, Q3T094, Q42942, Q4V831, Q4V9P6, Q5BJY6, Q5R7M2, Q5R824, Q5R9Y6, Q5RDK5, Q5U4Q9, Q5ZKP6, Q60HD7, Q62951, Q66IQ6, Q68FT9, Q6AY46, Q6P0U0, Q80XC2, Q8IW45

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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
Factors involved in megakaryocyte development and platelet production	5	9.8×	5e-03
Membrane Trafficking	6	6.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
microtubule cytoskeleton organization	5	13.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	100
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
57403	GRCh38/hg38 10q26.12-26.3(chr10:120454430-133620674)x1	Pathogenic
815385	GRCh37/hg19 10q26.2-26.3(chr10:129009772-135427143)x1	Pathogenic

SpliceAI

2486 predictions. Top by Δscore:

Variant	Effect	Δscore
10:132190741:C:A	acceptor_gain	1.0000
10:132190745:A:AG	acceptor_gain	1.0000
10:132190746:G:GG	acceptor_gain	1.0000
10:132190746:GA:G	acceptor_gain	1.0000
10:132190746:GAGT:G	acceptor_gain	1.0000
10:132190832:TAAA:T	donor_gain	1.0000
10:132190832:TAAAG:T	donor_loss	1.0000
10:132190833:AAA:A	donor_gain	1.0000
10:132190833:AAAG:A	donor_loss	1.0000
10:132190834:AA:A	donor_gain	1.0000
10:132190834:AAG:A	donor_loss	1.0000
10:132190835:AGT:A	donor_loss	1.0000
10:132190836:G:GG	donor_gain	1.0000
10:132190837:TAA:T	donor_loss	1.0000
10:132192655:CAG:C	acceptor_loss	1.0000
10:132192656:A:AG	acceptor_gain	1.0000
10:132192656:A:C	acceptor_loss	1.0000
10:132192657:G:GA	acceptor_gain	1.0000
10:132192657:GA:G	acceptor_gain	1.0000
10:132192657:GAC:G	acceptor_gain	1.0000
10:132192657:GACA:G	acceptor_gain	1.0000
10:132192657:GACAA:G	acceptor_gain	1.0000
10:132192825:G:GT	donor_gain	1.0000
10:132192838:GATCT:G	donor_gain	1.0000
10:132192839:ATCT:A	donor_gain	1.0000
10:132192840:TCT:T	donor_gain	1.0000
10:132192840:TCTGT:T	donor_loss	1.0000
10:132192841:CTG:C	donor_loss	1.0000
10:132192842:TG:T	donor_loss	1.0000
10:132192843:G:GG	donor_gain	1.0000

AlphaMissense

3762 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:132200864:A:C	S331R	0.999
10:132200866:C:A	S331R	0.999
10:132200866:C:G	S331R	0.999
10:132201988:A:C	S385R	0.999
10:132201990:T:A	S385R	0.999
10:132201990:T:G	S385R	0.999
10:132203915:T:C	F539L	0.999
10:132203917:C:A	F539L	0.999
10:132203917:C:G	F539L	0.999
10:132198873:G:C	R238P	0.998
10:132198888:C:A	A243D	0.998
10:132201977:T:A	V381D	0.998
10:132202069:T:A	W412R	0.998
10:132202069:T:C	W412R	0.998
10:132198875:G:C	A239P	0.997
10:132198876:C:A	A239D	0.997
10:132202030:G:A	G399R	0.997
10:132202030:G:C	G399R	0.997
10:132192723:T:A	V65D	0.996
10:132196869:T:C	S163P	0.996
10:132198863:G:C	A235P	0.996
10:132198887:G:C	A243P	0.996
10:132200449:T:A	V302D	0.996
10:132200955:G:C	R361P	0.996
10:132200969:T:A	W366R	0.996
10:132200969:T:C	W366R	0.996
10:132202001:C:A	A389D	0.996
10:132202030:G:T	G399W	0.996
10:132202031:G:A	G399E	0.996
10:132202061:T:C	L409P	0.996

dbSNP variants (sampled 300 via entrez): RS1000082329 (10:132188867 G>A), RS1000128060 (10:132204303 C>T), RS1000160771 (10:132204551 G>A,C), RS1000318235 (10:132201040 T>C), RS1000329989 (10:132193947 A>C,G), RS1000433941 (10:132188319 G>A), RS1000440454 (10:132204321 G>T), RS1000486420 (10:132188605 C>G,T), RS1000656822 (10:132196607 G>A), RS1000708918 (10:132196760 G>C), RS1000757768 (10:132187586 C>T), RS1000927051 (10:132192534 C>T), RS1000942245 (10:132192603 C>A,T), RS1001063528 (10:132187784 C>G), RS1001193496 (10:132186890 T>C,G)

Disease associations

OMIM: gene MIM:608407 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_559	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009769	histidine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases methylation, increases expression	6
Benzo(a)pyrene	increases expression, affects methylation	5
methylmercuric chloride	increases expression, affects cotreatment	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Dactinomycin	affects cotreatment, increases expression, increases secretion	2
Doxorubicin	affects expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
tungsten carbide	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	increases abundance, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
tobacco tar	decreases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
caffeic acid	increases expression, increases reaction	1
beta-methylcholine	affects expression	1
4-methoxycinnamate methyl ester	increases expression, increases reaction	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1

Clinical trials (associated diseases)

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