PCDH10

Summary

PCDH10 (protocadherin 10, HGNC:13404) is a protein-coding gene on chromosome 4q28.3, encoding Protocadherin-10 (Q9P2E7). Potential calcium-dependent cell-adhesion protein.

This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This family member contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein is a cadherin-related neuronal receptor thought to function in the establishment of specific cell-cell connections in the brain. This gene plays a role in inhibiting cancer cell motility and cell migration. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 57575 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 137 total
• MANE Select transcript: NM_032961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13404
Approved symbol	PCDH10
Name	protocadherin 10
Location	4q28.3
Locus type	gene with protein product
Status	Approved
Aliases	OL-PCDH, KIAA1400
Ensembl gene	ENSG00000138650
Ensembl biotype	protein_coding
OMIM	608286
Entrez	57575

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000264360, ENST00000511112, ENST00000618019

RefSeq mRNA: 2 — MANE Select: NM_032961 NM_020815, NM_032961

CCDS: CCDS34063, CCDS75192

Canonical transcript exons

ENST00000264360 — 5 exons

Exon	Start	End
ENSE00000935188	133154307	133154365
ENSE00000935189	133154917	133155023
ENSE00001209461	133149294	133152771
ENSE00001481579	133190141	133194700
ENSE00003539296	133162977	133163282

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 92.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.0152 / max 2153.0421, expressed in 1038 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49670	23.3669	927
49671	0.3304	189
49673	0.2656	101
49676	0.2613	106
49675	0.2493	165
203336	0.2303	96
49677	0.1501	83
49674	0.0657	29
49678	0.0578	31
49679	0.0379	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	92.45	gold quality
prefrontal cortex	UBERON:0000451	92.03	gold quality
medial globus pallidus	UBERON:0002477	91.38	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.35	gold quality
caudate nucleus	UBERON:0001873	90.32	gold quality
globus pallidus	UBERON:0001875	89.84	gold quality
nucleus accumbens	UBERON:0001882	89.67	gold quality
frontal cortex	UBERON:0001870	89.33	gold quality
superior frontal gyrus	UBERON:0002661	89.17	gold quality
Brodmann (1909) area 23	UBERON:0013554	88.77	gold quality
stromal cell of endometrium	CL:0002255	88.69	gold quality
putamen	UBERON:0001874	88.64	gold quality
neocortex	UBERON:0001950	88.41	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.35	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.24	gold quality
middle temporal gyrus	UBERON:0002771	87.87	gold quality
entorhinal cortex	UBERON:0002728	87.79	gold quality
primary visual cortex	UBERON:0002436	87.66	gold quality
corpus callosum	UBERON:0002336	87.62	gold quality
seminal vesicle	UBERON:0000998	87.49	gold quality
cerebral cortex	UBERON:0000956	87.37	gold quality
postcentral gyrus	UBERON:0002581	87.37	gold quality
cortical plate	UBERON:0005343	87.02	gold quality
anterior cingulate cortex	UBERON:0009835	86.90	gold quality
substantia nigra pars compacta	UBERON:0001965	86.89	gold quality
ascending aorta	UBERON:0001496	86.71	gold quality
temporal lobe	UBERON:0001871	86.67	gold quality
parietal lobe	UBERON:0001872	86.63	gold quality
thoracic aorta	UBERON:0001515	86.60	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	146.83
E-MTAB-7008	yes	128.36
E-MTAB-5061	yes	14.10
E-GEOD-81608	yes	10.54
E-ENAD-27	yes	5.07
E-MTAB-8060	no	59.11
E-ANND-3	no	5.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, DNMT3B, MEF2A, PAX3

miRNA regulators (miRDB)

218 targeting PCDH10, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754

Literature-anchored findings (GeneRIF, showing 40)

• Ectopic expression of PCDH10 strongly suppressed tumor cell growth, migration, invasion and colony formation. (PMID:16247458)
• These results suggest that OL-pc remodels the motility and adhesion machinery at cell junctions by recruiting the Nap1-WAVE1 complex to these sites and, in turn, promotes the migration of cells. (PMID:18644894)
• PCDH10 is a gastric tumor suppressor; its methylation at early stages of gastric carcinogenesis is an independent prognostic factor. (PMID:19084528)
• The role of OL-protocadherin-dependent striatal axon growth in neural circuit formation. (PMID:19262141)
• Showed aberrant promoter hypermethylation of PCDH10 is assoc’d with downreg’n of gene expression in cervical cancer, and the promoter methylation in the PCDH10 gene occurs at an earliest identifiable stage of low-grade squamous intraepithelial lesion. (PMID:19681120)
• field methylation of the PCDH10 gene specifically in the invasion stage of cervical carcinogenesis, which might be used to develop a highly specific diagnostic test for cervical scrapings. (PMID:19709077)
• epigenetic regulation of PCDH10 was associated with carcinogenesis. (PMID:20353276)
• Sp1/Sp3 and CBF/NF-Y transcription factors play a crucial role in the basal expression of the human PCDH10 gene. (PMID:21237250)
• The decreased PCDH10 expression in prostate cancer cells was associated with the aberrant methylation of PCDH10 promoter CpG islands. (PMID:21314642)
• genetic and epigenetic deregulation of PCDH10 occurs in a significant portion of medulloblastoma patients (PMID:21597995)
• PCDH10 promoter hypermethylation was frequent in both B-cell (81.9%) and T-cell (80%) acute lymphoblastic leukemia (ALL). (PMID:21960365)
• Data show that expression of PCDH10 is markedly reduced in gastric cancer cells and tissues, and suggest that it functions as a tumor suppressor gene in gastric cancer. (PMID:22206871)
• PCDH10 gene is a target for epigenetic silencing in multiple myeloma and provides a link between the dysregulation of angiogenesis and DNA methylation. (PMID:22245948)
• The expression of PCDH10 was silenced in hepatocellular carcinoma via de novo DNA methylation. (PMID:22543497)
• PCDH10 methylation is closely associated with malignancy of bladder transitional cell carcinoma (PMID:23171734)
• PCDH10 is an important tumor suppression gene with key roles of suppressing cell proliferation, clonogenicity, and inhibiting cell invasion in the development of colorectal cancer. (PMID:23180019)
• PCDH10 promoter methylation was detected in 59/117 (50.4%) of patients with bladder cancer, and none of 37 (0%) controls. Methylation was significantly associated with advanced stage, high grade, tumour recurrence and larger tumour size. (PMID:23321168)
• PCDH10 is frequently downregulated by promoter methylation and may serve as a tumor suppressor gene in non-small cell lung cancer. (PMID:23321465)
• Downregulated PCDH10 levels correlated with malignant behaviour and poor overall survival in patients with bladder cancer. (PMID:23569128)
• There was a significant correlation between PCDH10 methylation in cfDNA and tumour tissue in patients with early CRC. (PMID:23839493)
• study suggests that PCDH10 methylation occurs early in lymphomagenesis. PCDH10 expression was down regulated via promoter hypermethylation in T- and B-cell lymphoma cell lines (PMID:23929756)
• These results indicate that promoter methylation status of PCDH10, SPARC, and UCHL1 may be used both as prognostic and predictive molecular marker for colorectal cancer patients (PMID:24309322)
• suppression of the expression of PCDH10 by RNA interference induces the growth arrest and apoptosis of glioblastoma cells in vitro (PMID:24406169)
• Loss of PCDH10 expression is associated with metastasis in colorectal cancer. (PMID:24740680)
• Findings establish a novel PCDH10-Wnt/beta-catenin-MALAT1 regulatory axis that contributes to EEC development. (PMID:25085246)
• Aberrant methylation of PCDH10 predicts worse biochemical recurrence-free survival in patients with prostate cancer after radical prostatectomy. (PMID:25086586)
• Gastric cancer patients with 5 or more methylated CpG sites of PCDH10 promoter had significantly poorer survival. (PMID:25260683)
• These results suggest an important role of p53 in regulating tumor cell migration through activating PCDH10 expression. (PMID:25590240)
• PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/beta-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3beta and then to restrain the activation of beta-catenin (PMID:26081897)
• PCDH10 methylation is a potential biomarker that predicts a poor prognosis after curative resection of pathological stage I non-small-cell lung cancer. (PMID:26276761)
• Our present findings suggested that the hypermethylated CpG site counts of PCDH10 DNA promoter for evaluating the prognosis of GC was reasonable by using the D-BGS (PMID:26406945)
• Study found that hypermethylation of CpG probes in the promoter regions of HOXA9 and PCDH10 was associated with mature B-cell neoplasms. (PMID:26679037)
• we found that long noncoding RNA (lncRNA) MALAT1 binds EZH2, suppresses the tumor suppressor PCDH10, and promotes gastric cellular migration and invasion (PMID:26871474)
• PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer. (PMID:26881880)
• Data show that protocadherin 10 (PCDH10) over-expression could significantly induce cell apoptosis, and restrain proliferation, invasion and migration ability of BXPC-3 pancreatic cancer cells. (PMID:26927373)
• Results suggest that protocadherin 10 (PCDH10)-Dishevelled, EGL-10 and Pleckstrin domain containing 1 (DEPDC1)-caspase signaling may be a novel regulatory axis in endometrial endometrioid carcinoma (EEC) development. (PMID:26970279)
• These findings suggest that Pcdh10 may influence subcellular actin cytoskeletal organization and axon-axon interactions in the course of familial amyloidotic polyneuropathy (PMID:27338109)
• we found that the malignant character of GISTs was initiated and amplified by PCDH10 in a process regulated by HOTAIR. In summary, our findings imply that PCDH10 and HOTAIR may be useful markers of disease progression and therapeutic targets. (PMID:27659532)
• This study provides insights into the tumorigenesis and progression of hepatocellular carcinoma (HCC), and puts forward the novel hypothesis that PCDH10 could be a new biomarker for HCC, or that combined with other molecular markers could increase the specificity and sensitivity of diagnostic tests for HCC. Restoration of PCDH10 could be a valuable therapeutic target for HCC. (PMID:28498423)
• PCDH10 hypermethylation were found in 54.2% (58/107) of DLBCL cases, but only 12.5% (1/8) in reactive lymph node/follicular hyperplasia. (PMID:29202805)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcdh10a	ENSDARG00000099729
danio_rerio	pcdh10b	ENSDARG00000102824
mus_musculus	Pcdh10	ENSMUSG00000049100
rattus_norvegicus	Pcdh10	ENSRNOG00000031974

Paralogs (61): PCDHB4 (ENSG00000081818), PCDHA6 (ENSG00000081842), PCDHGA2 (ENSG00000081853), PCDHB2 (ENSG00000112852), PCDHB3 (ENSG00000113205), PCDHB5 (ENSG00000113209), PCDHB6 (ENSG00000113211), PCDHB7 (ENSG00000113212), PCDHB15 (ENSG00000113248), PCDH12 (ENSG00000113555), PCDH17 (ENSG00000118946), PCDHB8 (ENSG00000120322), PCDHB10 (ENSG00000120324), PCDHB14 (ENSG00000120327), PCDHB12 (ENSG00000120328), PCDH8 (ENSG00000136099), PCDH15 (ENSG00000150275), PCDH19 (ENSG00000165194), CDH16 (ENSG00000166589), PCDHB1 (ENSG00000171815), PCDHB9 (ENSG00000177839), PCDHB13 (ENSG00000187372), CDHR4 (ENSG00000187492), PCDH18 (ENSG00000189184), PCDHB11 (ENSG00000197479), PCDHGA1 (ENSG00000204956), PCDHA9 (ENSG00000204961), PCDHA8 (ENSG00000204962), PCDHA7 (ENSG00000204963), PCDHA5 (ENSG00000204965), PCDHA4 (ENSG00000204967), PCDHA2 (ENSG00000204969), PCDHA1 (ENSG00000204970), PCDHA13 (ENSG00000239389), PCDHGC3 (ENSG00000240184), PCDHGC5 (ENSG00000240764), PCDHGC4 (ENSG00000242419), PCDHAC2 (ENSG00000243232), PCDHAC1 (ENSG00000248383), PCDHA11 (ENSG00000249158)

Protein

Protein identifiers

Protocadherin-10 — Q9P2E7 (reviewed: Q9P2E7)

All UniProt accessions (2): Q9P2E7, X5D999

UniProt curated annotations — full annotation on UniProt →

Function. Potential calcium-dependent cell-adhesion protein. (Microbial infection) Acts as a receptor for Western equine encephalitis virus.

Subcellular location. Cell membrane.

Tissue specificity. Moderately expressed in all regions of the brain examined, as well as in testis and ovary, and low expression in all other tissues tested.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P2E7-1	1	yes
Q9P2E7-2	2

RefSeq proteins (2): NP_065866, NP_116586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR013164	Cadherin_N	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR032455	Cadherin_C	Domain
IPR050174	Protocadherin/Cadherin-CA	Family

Pfam: PF00028, PF08266, PF16492

UniProt features (93 total): strand 51, helix 11, turn 10, domain 6, region of interest 3, compositionally biased region 3, glycosylation site 2, splice variant 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6VFQ	X-RAY DIFFRACTION	2.3
9L41	ELECTRON MICROSCOPY	2.99
6VG4	X-RAY DIFFRACTION	3.3
9DQV	ELECTRON MICROSCOPY	3.3
9L1N	ELECTRON MICROSCOPY	3.3
6VFW	X-RAY DIFFRACTION	3.6
9E96	ELECTRON MICROSCOPY	4.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2E7-F1	73.89	0.53

Functional residue map

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

Glycosylation sites (2): 273, 557

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): CREL_01, GOZGIT_ESR1_TARGETS_DN, TATTATA_MIR374, LHX3_01, CCATCCA_MIR432, NFKB_Q6, GOBP_CELL_CELL_ADHESION, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, CAGCAGG_MIR370, TGCTGAY_UNKNOWN, WTGAAAT_UNKNOWN, TGTGTGA_MIR377, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, AAAGACA_MIR511, AACTTT_UNKNOWN

GO Biological Process (3): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), nervous system development (GO:0007399)

GO Molecular Function (2): calcium ion binding (GO:0005509), cell adhesion molecule binding (GO:0050839)

GO Cellular Component (4): plasma membrane (GO:0005886), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
cell-cell adhesion	1
system development	1
metal ion binding	1
protein binding	1
membrane	1
cell periphery	1
synaptic membrane	1
postsynapse	1
synapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1147 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCDH10	CDH2	P19022	897
PCDH10	SCN1A	P35498	858
PCDH10	STXBP1	P61764	842
PCDH10	DIPK2A	Q8NDZ4	840
PCDH10	CDKL5	O76039	830
PCDH10	KCNQ2	O43526	827
PCDH10	SLC25A22	Q9H936	809
PCDH10	SCN2A	Q99250	781
PCDH10	PNKP	Q96T60	754
PCDH10	ARHGEF9	O43307	733
PCDH10	SPTAN1	Q13813	708
PCDH10	PLCB1	Q9NQ66	664
PCDH10	MECP2	P51608	638
PCDH10	ARX	Q96QS3	627
PCDH10	GABRG2	P18507	603

IntAct

47 interactions, top by confidence:

A	B	Type	Score
ABI2	CYFIP1	psi-mi:“MI:0915”(physical association)	0.870
HSPC300	SCAR	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
BRK1	CYFIP1	psi-mi:“MI:0914”(association)	0.640
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
PCDH10	CYFIP1	psi-mi:“MI:0915”(physical association)	0.400
ABI2	PCDH17	psi-mi:“MI:0915”(physical association)	0.400
PCDHGB4	FAM171A2	psi-mi:“MI:0914”(association)	0.350
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
PCDH12	PCDH17	psi-mi:“MI:0914”(association)	0.350
PTGIR	GPAA1	psi-mi:“MI:0914”(association)	0.350
SLC34A2	SYNGR2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ATP1A3	TMEM223	psi-mi:“MI:0914”(association)	0.350
PCDH10	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-RNA), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS), MAGI1 (Affinity Capture-MS), MYADM (Affinity Capture-MS), RNFT1 (Affinity Capture-MS), PCDH10 (Affinity Capture-MS)

ESM2 similar proteins: D3ZE55, O14917, O35161, O95206, Q5DRE1, Q5DRE2, Q5DRE3, Q5DRE4, Q5DRE5, Q5DRE6, Q5DRE7, Q5DRE8, Q5DRE9, Q5DRF0, Q5DRF1, Q5DRF2, Q5DRF3, Q5DRF4, Q5DRF5, Q5JZY3, Q63315, Q6PFX6, Q767I8, Q7TSK3, Q86UP0, Q8BYG9, Q91Y11, Q91Y13, Q91Y20, Q91ZI0, Q9H158, Q9NPG4, Q9NYQ6, Q9NYQ7, Q9P2E7, Q9UJ99, Q9UN72, Q9UN73, Q9UN74, Q9UN75

Diamond homologs: A7MB46, D3ZE55, F8W3X3, O14917, O55134, O60330, O88689, O95206, Q5DRA2, Q5DRA3, Q5DRA4, Q5DRA5, Q5DRA6, Q5DRA7, Q5DRA8, Q5DRA9, Q5DRB0, Q5DRB1, Q5DRB2, Q5DRB3, Q5DRB4, Q5DRB5, Q5DRB6, Q5DRB7, Q5DRB8, Q5DRB9, Q5DRC0, Q5DRC1, Q5DRC2, Q5DRC6, Q5DRD3, Q5DRD6, Q5DRE0, Q5DRE1, Q5DRE3, Q5DRE4, Q5DRE5, Q5DRE6, Q5DRE7, Q5DRE8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PCDH10	“up-regulates activity”	ITGB1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

641 predictions. Top by Δscore:

Variant	Effect	Δscore
4:133153407:C:G	donor_gain	1.0000
4:133153428:T:G	donor_gain	1.0000
4:133153432:GA:G	donor_gain	1.0000
4:133153434:G:GG	donor_gain	1.0000
4:133154305:A:AG	acceptor_gain	1.0000
4:133154306:G:GA	acceptor_gain	1.0000
4:133154362:ACAGG:A	donor_loss	1.0000
4:133154363:CAGGT:C	donor_loss	1.0000
4:133154364:AGGTA:A	donor_loss	1.0000
4:133154365:GG:G	donor_loss	1.0000
4:133154366:G:GA	donor_loss	1.0000
4:133154367:T:G	donor_loss	1.0000
4:133154915:A:AG	acceptor_gain	1.0000
4:133154916:G:GG	acceptor_gain	1.0000
4:133154916:GTTC:G	acceptor_gain	1.0000
4:133154916:GTTCT:G	acceptor_gain	1.0000
4:133155020:GCTG:G	donor_gain	1.0000
4:133155024:G:GA	donor_loss	1.0000
4:133155024:G:GG	donor_gain	1.0000
4:133155025:T:A	donor_loss	1.0000
4:133162971:TTACA:T	acceptor_loss	1.0000
4:133162972:TACA:T	acceptor_loss	1.0000
4:133162975:AGGTA:A	acceptor_loss	1.0000
4:133162976:GGT:G	acceptor_gain	1.0000
4:133162976:GGTAT:G	acceptor_gain	1.0000
4:133163278:TTTGA:T	donor_gain	1.0000
4:133163279:TTGA:T	donor_gain	1.0000
4:133163279:TTGAG:T	donor_loss	1.0000
4:133163280:TGA:T	donor_gain	1.0000
4:133163280:TGAGT:T	donor_loss	1.0000

AlphaMissense

6761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:133150505:T:G	F122C	1.000
4:133150640:T:C	F167S	1.000
4:133150688:T:C	L183P	1.000
4:133150712:G:C	R191P	1.000
4:133150865:A:T	D242V	1.000
4:133150874:A:C	D245A	1.000
4:133150874:A:T	D245V	1.000
4:133150883:C:A	P248H	1.000
4:133151063:G:A	G308D	1.000
4:133151207:C:A	P356Q	1.000
4:133151272:G:C	A378P	1.000
4:133151273:C:A	A378D	1.000
4:133151276:T:C	L379P	1.000
4:133151348:T:C	F403S	1.000
4:133151384:T:A	I415N	1.000
4:133151444:C:A	A435D	1.000
4:133151504:A:T	D455V	1.000
4:133151510:A:T	N457I	1.000
4:133151511:C:A	N457K	1.000
4:133151511:C:G	N457K	1.000
4:133151513:A:C	D458A	1.000
4:133151513:A:T	D458V	1.000
4:133151522:C:A	P461Q	1.000
4:133151527:T:C	F463L	1.000
4:133151528:T:G	F463C	1.000
4:133151529:C:A	F463L	1.000
4:133151529:C:G	F463L	1.000
4:133151561:A:T	E474V	1.000
4:133151568:C:A	N476K	1.000
4:133151568:C:G	N476K	1.000

dbSNP variants (sampled 300 via entrez): RS1000051863 (4:133207186 G>A), RS10000633 (4:133191997 T>A), RS10000634 (4:133191998 T>C,G), RS1000078922 (4:133157488 T>C,G), RS1000129848 (4:133157172 G>T), RS1000160622 (4:133170020 T>C), RS1000178040 (4:133173233 A>C), RS1000216188 (4:133184084 C>T), RS1000242137 (4:133205857 T>C), RS1000314615 (4:133184303 G>A), RS1000378485 (4:133206021 A>G), RS1000388780 (4:133163702 A>G), RS1000397816 (4:133170219 T>C), RS1000444003 (4:133156905 A>G), RS1000474747 (4:133164285 C>G)

Disease associations

OMIM: gene MIM:608286 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autism	Limited	Autosomal dominant

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002927_21	Mercury levels	4.000000e-06
GCST003026_11	Yu-Zhi constitution type in type 2 diabetes	6.000000e-06
GCST006466_1	Endometrial cancer (Non-endometrioid histology)	1.000000e-07
GCST009103_3	Resistance to antihypertensive treatment in hypertension	2.000000e-06
GCST010566_4	Benign childhood epilepsy with centro-temporal spikes	8.000000e-06
GCST011122_53	Walking pace	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007638	Yu-Zhi constitution type
EFO:1002006	treatment-resistant hypertension

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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
trichostatin A	affects cotreatment, increases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Estradiol	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
methylmercuric chloride	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cytochalasin H	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment	1
epigallocatechin gallate	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Coumestrol	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1

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