DPYSL5

Summary

DPYSL5 (dihydropyrimidinase like 5, HGNC:20637) is a protein-coding gene on chromosome 2p23.3, encoding Dihydropyrimidinase-related protein 5 (Q9BPU6). Involved in the negative regulation of dendrite outgrowth.

This gene encodes a member of the CRMP (collapsing response mediator protein) family thought to be involved in neural development. Antibodies to the encoded protein were found in some patients with neurologic symptoms who had paraneoplastic syndrome. A pseudogene of this gene is found on chromosome 11. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 56896 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ritscher-Schinzel syndrome 4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 17
• Clinical variants (ClinVar): 132 total — 1 pathogenic
• Phenotypes (HPO): 109
• MANE Select transcript: NM_020134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20637
Approved symbol	DPYSL5
Name	dihydropyrimidinase like 5
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	CRMP5, Ulip6, CRMP-5, CRAM, CV2
Ensembl gene	ENSG00000157851
Ensembl biotype	protein_coding
OMIM	608383
Entrez	56896

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000288699, ENST00000401478, ENST00000431402, ENST00000434719, ENST00000450961, ENST00000484882, ENST00000614712, ENST00000896871, ENST00000967335

RefSeq mRNA: 3 — MANE Select: NM_020134 NM_001253723, NM_001253724, NM_020134

CCDS: CCDS1730

Canonical transcript exons

ENST00000288699 — 13 exons

Exon	Start	End
ENSE00001180845	26946910	26950351
ENSE00001275547	26848132	26848254
ENSE00001625030	26934578	26934734
ENSE00001681164	26933258	26933333
ENSE00001695162	26928255	26928323
ENSE00001744511	26924887	26925045
ENSE00001776901	26940031	26940172
ENSE00001797264	26927253	26927432
ENSE00001799955	26931640	26931684
ENSE00002173045	26898496	26898760
ENSE00003641641	26944656	26944824
ENSE00003649370	26942543	26942750
ENSE00003652708	26941950	26942092

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.14.

FANTOM5 (CAGE): breadth broad, TPM avg 12.0542 / max 2333.7886, expressed in 458 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19283	8.4859	447
19296	0.7701	139
19295	0.5982	131
19294	0.5484	137
19293	0.4408	126
19284	0.4003	157
19282	0.3006	211
19292	0.1572	90
19287	0.0799	44
19291	0.0710	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.14	gold quality
ganglionic eminence	UBERON:0004023	98.79	gold quality
ventricular zone	UBERON:0003053	98.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.16	gold quality
spinal cord	UBERON:0002240	96.32	gold quality
nucleus accumbens	UBERON:0001882	91.24	gold quality
putamen	UBERON:0001874	89.65	gold quality
substantia nigra	UBERON:0002038	89.64	gold quality
caudate nucleus	UBERON:0001873	89.58	gold quality
corpus callosum	UBERON:0002336	89.42	gold quality
hypothalamus	UBERON:0001898	89.12	gold quality
inferior vagus X ganglion	UBERON:0005363	88.56	gold quality
midbrain	UBERON:0001891	88.41	gold quality
prefrontal cortex	UBERON:0000451	88.12	gold quality
pancreatic ductal cell	CL:0002079	88.04	silver quality
right hemisphere of cerebellum	UBERON:0014890	86.12	gold quality
cerebellar hemisphere	UBERON:0002245	85.98	gold quality
cerebellar cortex	UBERON:0002129	85.92	gold quality
sperm	CL:0000019	85.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.73	gold quality
cerebellum	UBERON:0002037	84.82	gold quality
right frontal lobe	UBERON:0002810	84.73	gold quality
anterior cingulate cortex	UBERON:0009835	84.46	gold quality
neocortex	UBERON:0001950	84.06	gold quality
frontal cortex	UBERON:0001870	83.78	gold quality
frontal lobe	UBERON:0016525	83.78	gold quality
brain	UBERON:0000955	83.77	gold quality
forebrain	UBERON:0001890	83.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.25	gold quality
subthalamic nucleus	UBERON:0001906	82.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

199 targeting DPYSL5, 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-6867-5P	100.00	82.21	3464
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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777

Literature-anchored findings (GeneRIF, showing 13)

• CRMP-5-IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. (PMID:12838519)
• CRMP-5 autoimmune myelopathy and occult neoplasia are important considerations in patients with insidiously progressive myelopathy, especially with known cancer risk. (PMID:18306241)
• We describe a patient with optic neuropathy and vitritis as the only clinical manifestations of paraneoplastic optic neuropathy secondary to lung cancer marked by an extremely high titer of CRMP-5 antibody. (PMID:18347453)
• findings point at CRMP5 as a novel marker for distinguishing between highly aggressive neuroendocrine carcinoma and the other lung cancers. (PMID:18769332)
• patients with CV2/CRMP5-Ab and thymoma developed myasthenic syndrome more frequently (PMID:18931014)
• New CRMP5 isoform present in the nucleus is associated with Glioma. (PMID:23298946)
• identified residues that are crucial for determining the preference for hetero-oligomer or homo-oligomer formation. In spite of being the CRMP family member most closely related to dihydropyrimidinase, CRMP-5 does not have amidohydrolase activity. (PMID:23373749)
• study elucidates a novel regulatory mechanism that utilizes CRMP5-induced mitophagy to orchestrate proper dendrite outgrowth and neuronal function. (PMID:24324268)
• present study suggested that CRAM could be a clinical prognostic marker for patients with cervical cancer (PMID:24695578)
• Our findings suggest that CRMP5 serves as a major mediator of Notch signaling and Akt activation by controlling the degradation of the Notch receptor, with implications for defining a biomarker signature in glioblastoma (PMID:26122847)
• Study describes the relevance of DRP5 during osteosarcoma development. DRP5 was upregulated in osteosarcoma specimens and cell lines and shown to function via the downstream MMPs. Inhibition of DRP5 suppressed the growth of cancer cells in vitro and in vivo, and high expression levels of DRP5 were associated with poor prognosis in osteosarcoma patients. (PMID:28374915)
• High CRMP5 expression is associated with prostate cancer. (PMID:31403941)
• Missense variants in DPYSL5 cause a neurodevelopmental disorder with corpus callosum agenesis and cerebellar abnormalities. (PMID:33894126)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpysl5a	ENSDARG00000011141
danio_rerio	dpysl5b	ENSDARG00000059311
mus_musculus	Dpysl5	ENSMUSG00000029168
rattus_norvegicus	Dpysl5	ENSRNOG00000008996
caenorhabditis_elegans		WBGENE00006769

Paralogs (5): CRMP1 (ENSG00000072832), DPYSL2 (ENSG00000092964), DPYSL3 (ENSG00000113657), DPYS (ENSG00000147647), DPYSL4 (ENSG00000151640)

Protein

Protein identifiers

Dihydropyrimidinase-related protein 5 — Q9BPU6 (reviewed: Q9BPU6)

Alternative names: CRMP3-associated molecule, Collapsin response mediator protein 5, UNC33-like phosphoprotein 6

All UniProt accessions (4): E7ESV0, E7EWB4, E9PHT0, Q9BPU6

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the negative regulation of dendrite outgrowth.

Subunit / interactions. Homotetramer, and heterotetramer with other DPYS-like proteins. Interacts with DPYSL2, DPYSL3 and DPYSL4. Interacts with MAP2 and TUBB3.

Subcellular location. Cytoplasm.

Disease relevance. Ritscher-Schinzel syndrome 4 (RTSC4) [MIM:619435] An autosomal dominant form of Ritscher-Schinzel syndrome, a developmental malformation syndrome characterized by cerebellar brain anomalies associated with global developmental delay and impaired intellectual development, congenital heart defects, and craniofacial abnormalities. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (3): NP_001240652, NP_001240653, NP_064519* (*=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 (56 total): helix 20, strand 19, turn 6, modified residue 5, sequence conflict 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4B91	X-RAY DIFFRACTION	1.7
4B90	X-RAY DIFFRACTION	2.2
4B92	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BPU6-F1	91.21	0.85

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 (5): 509, 514, 532, 538, 559

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-399956	CRMPs in Sema3A signaling

MSigDB gene sets: 419 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GCANCTGNY_MYOD_Q6, MODULE_418, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, CTATGCA_MIR153, GGGTGGRR_PAX4_03, GGAMTNNNNNTCCY_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_PYRIMIDINE_NUCLEOBASE_METABOLIC_PROCESS, EFC_Q6

GO Biological Process (5): signal transduction (GO:0007165), nervous system development (GO:0007399), axon guidance (GO:0007411), negative regulation of dendrite morphogenesis (GO:0050774), neuron differentiation (GO:0030182)

GO Molecular Function (4): hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides (GO:0016812), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds (GO:0016810)

GO Cellular Component (7): cytosol (GO:0005829), dendrite (GO:0030425), protein-containing complex (GO:0032991), neuronal cell body (GO:0043025), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), synapse (GO:0045202)

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
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
axonogenesis	1
neuron projection guidance	1
negative regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
negative regulation of neurogenesis	1
cell differentiation	1
generation of neurons	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
binding	1
catalytic activity	1
hydrolase activity	1
cytoplasm	1
neuron projection	1
dendritic tree	1
cellular_component	1
somatodendritic compartment	1
cell body	1
synapse	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPYSL5	AMPH	P49418	883
DPYSL5	PNMA2	Q9UL42	881
DPYSL5	BIN1	O00499	872
DPYSL5	LGI1	O95970	872
DPYSL5	SLC6A5	Q9Y345	836
DPYSL5	CNTNAP2	Q9UHC6	810
DPYSL5	GLRA1	P23415	785
DPYSL5	ZIC4	Q8N9L1	765
DPYSL5	GAD2	Q05329	739
DPYSL5	SDCBP	O00560	735
DPYSL5	DPP10	Q8N608	720
DPYSL5	DPP6	P42658	717
DPYSL5	IGLON5	A6NGN9	698
DPYSL5	SOX1	O00570	694
DPYSL5	DNER	Q8NFT8	694

IntAct

137 interactions, top by confidence:

A	B	Type	Score
DPYSL2	DPYSL5	psi-mi:“MI:0915”(physical association)	0.900
DPYSL5	DPYSL2	psi-mi:“MI:0915”(physical association)	0.900
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
DPYSL5	DPYSL4	psi-mi:“MI:0914”(association)	0.640
CFAP161	DPYSL5	psi-mi:“MI:0915”(physical association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
DPYSL3	DPYSL4	psi-mi:“MI:0914”(association)	0.640
SAMTOR	DEPDC5	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
DPYSL3	DPYSL5	psi-mi:“MI:0915”(physical association)	0.560
CASP6	DPYSL5	psi-mi:“MI:0915”(physical association)	0.560
DPYSL5	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	DPYSL5	psi-mi:“MI:0915”(physical association)	0.560
DPYSL5	GSN	psi-mi:“MI:0915”(physical association)	0.560
DPYSL5	HIP1	psi-mi:“MI:0915”(physical association)	0.560
DPYSL5	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	DPYSL5	psi-mi:“MI:0915”(physical association)	0.560
NDUFS1	DPYSL5	psi-mi:“MI:0915”(physical association)	0.560
DPYSL5	PEX1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (97): DPYSL5 (Two-hybrid), DPYSL5 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL4 (Affinity Capture-MS), DPYSL2 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), INPPL1 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G4P2K0, A0A109QYD3, A0A348AXY0, A1JN45, A6T7D6, A7MGD2, B4TET5, B5XXJ5, B6EPQ0, C3K630, C3K6Z4, J9U5U9, O07015, O18391, O45583, P04968, P06204, P0DXI6, P0DXI7, P0DXI8, P23133, P23974, P24069, P46541, P53750, Q01399, Q0D1W9, Q10J20, Q10QA5, Q2IYT0, Q2NQH6, Q2TZN9, Q2Y9Y7, Q47595, Q4X1Q4, Q52PJ5, Q62951, Q6DGG1, Q76KX0, Q7N9V7

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

2 interactions.

A	Effect	B	Mechanism
GSK3B	“up-regulates activity”	DPYSL5	phosphorylation
DPYSL5	“down-regulates activity”	MAP2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
Apoptosis	5	12.9×	6e-03
Programmed Cell Death	5	11.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	104
Likely benign	21
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1184280	NM_020134.4(DPYSL5):c.121G>A (p.Glu41Lys)	Pathogenic

SpliceAI

2373 predictions. Top by Δscore:

Variant	Effect	Δscore
2:26848252:GGA:G	donor_gain	1.0000
2:26848253:GAG:G	donor_gain	1.0000
2:26848255:G:GG	donor_gain	1.0000
2:26898493:TA:T	acceptor_loss	1.0000
2:26898494:A:AT	acceptor_loss	1.0000
2:26898494:AG:A	acceptor_gain	1.0000
2:26898495:GG:G	acceptor_gain	1.0000
2:26898495:GGA:G	acceptor_gain	1.0000
2:26898495:GGAA:G	acceptor_gain	1.0000
2:26898495:GGAAC:G	acceptor_gain	1.0000
2:26898758:AAGG:A	donor_loss	1.0000
2:26898759:AGGTA:A	donor_loss	1.0000
2:26898760:GGTAA:G	donor_loss	1.0000
2:26898761:G:T	donor_loss	1.0000
2:26927347:G:GG	donor_gain	1.0000
2:26927379:G:GT	donor_gain	1.0000
2:26928242:T:TA	acceptor_gain	1.0000
2:26928245:T:A	acceptor_gain	1.0000
2:26928253:A:AG	acceptor_gain	1.0000
2:26928253:AG:A	acceptor_gain	1.0000
2:26928254:G:GG	acceptor_gain	1.0000
2:26928254:GG:G	acceptor_gain	1.0000
2:26928254:GGGT:G	acceptor_gain	1.0000
2:26928320:GGAG:G	donor_gain	1.0000
2:26928321:GAGG:G	donor_gain	1.0000
2:26928322:AGG:A	donor_loss	1.0000
2:26928323:GGTG:G	donor_loss	1.0000
2:26928324:G:C	donor_loss	1.0000
2:26928325:T:G	donor_loss	1.0000
2:26933252:GTTTA:G	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000014281 (2:26857781 T>A), RS1000091783 (2:26849406 G>C,T), RS1000123583 (2:26894748 A>C,G), RS1000152359 (2:26867244 T>C), RS1000187712 (2:26848410 G>T), RS1000192972 (2:26896507 T>A), RS1000263766 (2:26876569 G>A), RS1000273602 (2:26921322 A>C,G), RS1000356325 (2:26888594 T>C), RS1000375592 (2:26869873 T>A,C), RS1000379937 (2:26915532 C>T), RS1000380566 (2:26860347 G>A), RS1000385008 (2:26907489 G>C,T), RS1000438954 (2:26863052 G>A,T), RS1000467939 (2:26902097 C>A,T)

Disease associations

OMIM: gene MIM:608383 | disease phenotypes: MIM:619435, MIM:220200, MIM:220210

GenCC curated gene-disease

Disease	Classification	Inheritance
Ritscher-Schinzel syndrome 4	Strong	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

Mondo (5): Ritscher-Schinzel syndrome 4 (MONDO:0030331), autism spectrum disorder (MONDO:0005258), Dandy-Walker syndrome (MONDO:0009072), Ritscher-Schinzel syndrome 1 (MONDO:0009073), syndromic intellectual disability (MONDO:0000508)

Orphanet (4): Isolated Dandy-Walker malformation (Orphanet:217), Syndrome with a Dandy-Walker malformation as a major feature (Orphanet:269546), 3C syndrome (Orphanet:7), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

109 total (30 of 109 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000235	Abnormal cranial suture/fontanelle morphology
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000269	Prominent occiput
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000329	Facial hemangioma
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000400	Macrotia
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000520	Proptosis

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001527_4	Fasting blood glucose (BMI interaction)	2.000000e-12
GCST001762_350	Obesity-related traits	5.000000e-06
GCST004068_11	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	3.000000e-06
GCST005186_3	Fasting blood glucose	3.000000e-11
GCST007679_2	Reflection (response to stress)	7.000000e-06
GCST008971_24	Urate levels	8.000000e-06
GCST008972_49	Urate levels	5.000000e-06
GCST008972_69	Urate levels	3.000000e-10
GCST010697_14	Cortical surface area (min-P)	2.000000e-09
GCST010698_75	Subcortical volume (min-P)	2.000000e-13
GCST010699_41	Brain morphology (min-P)	2.000000e-08
GCST010700_38	Cortical thickness (MOSTest)	3.000000e-08
GCST010701_56	Cortical surface area (MOSTest)	4.000000e-16
GCST010702_20	Subcortical volume (MOSTest)	2.000000e-64
GCST010703_76	Brain morphology (MOSTest)	1.000000e-16
GCST010796_4708	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST90002407_216	White blood cell count	5.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005116	urinary metabolite measurement
EFO:0009859	reflective stress response
EFO:0004531	urate measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003616	Dandy-Walker Syndrome	C10.228.140.252.300; C10.228.140.602.500; C10.500.205; C16.131.666.205

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
uranyl acetate	increases expression	1
propionaldehyde	increases expression	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
pentanal	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Aldehydes	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Fonofos	increases methylation	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Parathion	increases methylation	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	decreases expression	1
Uranium	increases expression	1
Aflatoxin B1	affects methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in 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
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
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
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder