PDCD10

Summary

PDCD10 (programmed cell death 10, HGNC:8761) is a protein-coding gene on chromosome 3q26.1, encoding Programmed cell death protein 10 (Q9BUL8). Promotes cell proliferation.

This gene encodes an evolutionarily conserved protein associated with cell apoptosis. The protein interacts with the serine/threonine protein kinase MST4 to modulate the extracellular signal-regulated kinase (ERK) pathway. It also interacts with and is phosphoryated by serine/threonine kinase 25, and is thought to function in a signaling pathway essential for vascular developent. Mutations in this gene are one cause of cerebral cavernous malformations, which are vascular malformations that cause seizures and cerebral hemorrhages. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 11235 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebral cavernous malformation 3 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 221 total — 75 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes
• MANE Select transcript: NM_007217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8761
Approved symbol	PDCD10
Name	programmed cell death 10
Location	3q26.1
Locus type	gene with protein product
Status	Approved
Aliases	TFAR15
Ensembl gene	ENSG00000114209
Ensembl biotype	protein_coding
OMIM	609118
Entrez	11235

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 43 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000392750, ENST00000461494, ENST00000462725, ENST00000462830, ENST00000464360, ENST00000470131, ENST00000471885, ENST00000473645, ENST00000475915, ENST00000479121, ENST00000481136, ENST00000483451, ENST00000487678, ENST00000487947, ENST00000492139, ENST00000492396, ENST00000494502, ENST00000497056, ENST00000877652, ENST00000877653, ENST00000877654, ENST00000877655, ENST00000877656, ENST00000877657, ENST00000877658, ENST00000877659, ENST00000877660, ENST00000877661, ENST00000877662, ENST00000877663, ENST00000877664, ENST00000877665, ENST00000877666, ENST00000877667, ENST00000877668, ENST00000877669, ENST00000877670, ENST00000877671, ENST00000935493, ENST00000935494, ENST00000935495, ENST00000935496, ENST00000935497, ENST00000935498, ENST00000935499, ENST00000956402, ENST00000956403, ENST00000956404

RefSeq mRNA: 3 — MANE Select: NM_007217 NM_007217, NM_145859, NM_145860

CCDS: CCDS3202

Canonical transcript exons

ENST00000392750 — 9 exons

Exon	Start	End
ENSE00000780150	167687234	167687316
ENSE00000780153	167687615	167687693
ENSE00001512946	167734214	167734350
ENSE00001512947	167734662	167734892
ENSE00001939660	167683298	167684389
ENSE00003536456	167695596	167695722
ENSE00003550733	167720062	167720273
ENSE00003581548	167697009	167697126
ENSE00003670459	167704842	167704895

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.4609 / max 1396.0671, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45459	41.2010	1812
45457	1.4227	657
45460	1.4120	895
45458	0.4252	189

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.43	gold quality
colonic mucosa	UBERON:0000317	98.26	gold quality
trabecular bone tissue	UBERON:0002483	98.14	gold quality
calcaneal tendon	UBERON:0003701	98.04	gold quality
oral cavity	UBERON:0000167	97.99	gold quality
epithelium of nasopharynx	UBERON:0001951	97.50	gold quality
palpebral conjunctiva	UBERON:0001812	97.37	gold quality
monocyte	CL:0000576	97.14	gold quality
mononuclear cell	CL:0000842	97.14	gold quality
leukocyte	CL:0000738	96.94	gold quality
skin of hip	UBERON:0001554	96.86	gold quality
gingiva	UBERON:0001828	96.72	gold quality
penis	UBERON:0000989	96.70	gold quality
pharyngeal mucosa	UBERON:0000355	96.66	gold quality
gingival epithelium	UBERON:0001949	96.65	gold quality
heart right ventricle	UBERON:0002080	96.56	gold quality
mammalian vulva	UBERON:0000997	96.27	gold quality
esophagus squamous epithelium	UBERON:0006920	96.19	gold quality
bone marrow	UBERON:0002371	96.13	gold quality
squamous epithelium	UBERON:0006914	96.08	gold quality
amniotic fluid	UBERON:0000173	96.06	gold quality
adult organism	UBERON:0007023	96.01	gold quality
bronchial epithelial cell	CL:0002328	95.96	gold quality
duodenum	UBERON:0002114	95.92	gold quality
oocyte	CL:0000023	95.89	gold quality
nasal cavity mucosa	UBERON:0001826	95.86	gold quality
epithelium of esophagus	UBERON:0001976	95.85	gold quality
nasal cavity epithelium	UBERON:0005384	95.84	gold quality
islet of Langerhans	UBERON:0000006	95.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.44

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
DLL4	Activation
FLT1	Activation
HES1	Activation
HEY2	Activation
KDR	Repression
MAPK1	Repression
MAPK3	Repression
NOTCH4	Activation
VEGFA	Repression

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

77 targeting PDCD10, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4302	99.89	67.94	1187

Literature-anchored findings (GeneRIF, showing 40)

• We report herein the identification of PDCD10 (programmed cell death 10) as the CCM3 gene. (PMID:15543491)
• KRIT1, Malcavernin, and PDCD10 are differentially expressed in cerebral venous malformations and cerebral cavernous malformations (PMID:16239636)
• Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3. (PMID:16284570)
• Sequence analysis of PDCD10 in a panel of 29 probands lacking Krit1 and MGC4607 mutations revealed only three mutations. (PMID:16329096)
• The authors screened the PCDC10 gene in 15 families that did not have a CCM1 or CCM2 mutation. Only two novel mutations were found, suggesting that mutations in this gene may only account for a small percentage of CCM familial cases. (PMID:16380626)
• Five percent of patients with familial cerebral cavernomas have retinal cavernomas. These lesions are clinically asymptomatic. They can be associated with any of the 3 cerebral cavernous malformation genes. (PMID:16769843)
• intergenic region of the head-to-head PDCD10-SERPINI1 gene pair provides an interesting and informative example of a complex regulatory system (PMID:17212813)
• Results show that PDCD10 modulation of ERK signaling is mediated by MST4, and that PDCD10 may be a regulatory adaptor necessary for MST4 function, suggesting a link between cerebral cavernous malformation and the ERK-MAPK cascade via PDCD10/MST4. (PMID:17360971)
• CCM3 (PDCD10) coprecipitates and colocalizes with CCM2. CCM3 directly binds to serine/threonine kinase 25 (STK25, YSK1, SOK1) and the phosphatase domain of Fas-associated phosphatase-1 (FAP-1, PTPN13, PTP-Bas, PTP-BL). (PMID:17657516)
• To the best of our knowledge, this is the first report of an association between a mutation in the PDCD10 gene and spinal cavernous malformations. (PMID:18035376)
• data are in agreement with a loss-of-function mechanism for CCM mutations, uncover an N-terminal CCM2 domain required for CCM1 binding, and demonstrate full-length CCM2 as the essential core protein in the CCM1/CCM2/CCM3 complex (PMID:18300272)
• Biallelic germline and somatic mutations were identified in CCM1, CCM2 or PDCD10 from all forms of inherited cerebral cavernous malformations. (PMID:19088123)
• Complete localized loss of either CCM1, CCM2 or CCM3 protein expression depend on the inherited mutation in cerebral cavernous malformations. (PMID:19088124)
• Multiplex Ligation-dependent Probe Amplification analysis integrates the consecutive sequence analysis of the 3 genes (Krit1/CCM1, MGC4607/CCM2, and PDCD10/CCM3) known to be responsible for cerebral cavernous malformation lesions. (PMID:19199464)
• CCM3 is both necessary and sufficient to induce apoptosis in vitro in well-defined cell culture systems (PMID:19246713)
• The newly mapped STK25 and MST4 interaction domain within the CCM3 protein plays a crucial role for vascular development in zebrafish. (PMID:19370760)
• We report multiple dural lesions mimicking meningiomas in patients with CCM3/PDCD10 mutations. (PMID:19506228)
• CCM3 protein contributes to vasculogenesis and angiogenesis in human placenta. (PMID:19688696)
• CCM3 is located on the Golgi apparatus, forming a complex with proteins of the germinal center kinase III (GCKIII) family and GM130, a Golgi-resident protein. (PMID:20332113)
• Genetic variations could interfere with the proper CCM1/CCM2/CCM3 protein complex, thus explaining the observed clinical variability in cerebral cavernous malformations in a large family. (PMID:20419355)
• CCM3 is a cerebral cavernous malformation protein critical for vascular integrity (PMID:20489202)
• In cultured human endothelial cells, CCM3 and STK25 regulated barrier function in a manner similar to CCM2, and STKs negatively regulated Rho by directly activating moesin. (PMID:20592472)
• A novel large CCM3 deletion is identified with typical magnetic resonance imaging in a patient and her daughter. (PMID:20623299)
• Study propose that the Cerebral cavernous malformations protein complex functions in the PI3K signaling pathway through the interaction between PDCD10 and PtdIns(3,4,5)P3. (PMID:20668527)
• The crystal structure of human PDCD10 complexed with inositol-(1,3,4,5)-tetrakisphosphate has been determined at 2.3A resolution. (PMID:20682288)
• PDCD10 can form complexes with other members of the CCM family, including CCM2, a key mediator of receptor tyrosine kinase-dependent cell death in neuroblastic tumors. (PMID:20854465)
• adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures (PMID:20862502)
• Among familial cases of Cerebral cavernous malformations 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3 (PMID:21029238)
• PDCD10/CCM3 acts as a critical regulator of neuronal survival during development (PMID:21041308)
• the crystal structures of CCM3 in complex with three different leucine-aspartate repeat (LD) motifs (LD1, LD2, and LD4) from the scaffolding protein paxillin (PMID:21632544)
• role of CCM3 and ezrin/radixin/moesin family of proteins in cell’s response to oxidative stress (PMID:22291017)
• PDCD10 might be a regulatory adaptor required for STK25 functions, which differ distinctly depending on the redox status of the cells that may be potentially related to tumor progression. (PMID:22652780)
• crystal of the CCM3-MST4 C-terminal domain complex belonged to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = 69.10, b = 69.10, c = 117.57 A (PMID:22750858)
• Loss of CCM3 impairs DLL4-Notch signalling and is associated with impaired endothelial angiogenesis and inherited cerebral cavernous malformations. (PMID:23388056)
• CCM3 mutations are associated with cerebral cavernous malformation in some Japanese patients. (PMID:23485406)
• CCM3 forms a stable complex with MST4 in vivo to promote cell proliferation and migration synergistically in a manner dependent on MST4 kinase activity. (PMID:23541896)
• DNA sequencing and deletion/duplication testing of the CCM1, CCM2, and CCM3 genes in the proband revealed a CCM1 c.601CNG mutation. (PMID:24007869)
• The identification of other four new mutations in 40 sporadic patients with either single or multiple cerebral cavernous malformations, is reported. (PMID:24058906)
• Prevalence, frequency and characterization of CCM1, CCM2 and CCM3 variants in cerebral cavernous malformation Spanish patients. (PMID:24466005)
• Study shows that PDCD10 mutations result in vascular permeability mediated by ROCK activity and a particularly severe clinical phenotype of patients and mouse model for cerebral cavernous malformation disease. (PMID:25122144)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdcd10b	ENSDARG00000012591
danio_rerio	pdcd10a	ENSDARG00000035054
mus_musculus	Pdcd10	ENSMUSG00000027835
rattus_norvegicus	Pdcd10	ENSRNOG00000010147
drosophila_melanogaster	Ccm3	FBGN0038331
caenorhabditis_elegans		WBGENE00007561

Protein

Protein identifiers

Programmed cell death protein 10 — Q9BUL8 (reviewed: Q9BUL8)

Alternative names: Cerebral cavernous malformations 3 protein, TF-1 cell apoptosis-related protein 15

All UniProt accessions (9): C9J363, C9J5C3, C9J6F3, C9J932, C9JND6, C9JSA3, Q9BUL8, F8WDF3, H7C5M9

UniProt curated annotations — full annotation on UniProt →

Function. Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and STK26 activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation. Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development.

Subunit / interactions. Homodimer. Interacts (via C-terminus) with CCM2. Interacts (via C-terminus) with PXN. Interacts (via N-terminus) with STK25. Interacts (via N-terminus) with STK26. Interacts (via N-terminus) with STK24. Interacts with GOLGA2. Identified in a complex with KRIT1 and CCM2. Interacts with KDR/VEGFR2. Interaction with KDR/VEGFR2 is enhanced by stimulation with VEGFA (Ref.5). Interacts with RIPOR1 (via C-terminus); this interaction is required for the association of RIPOR1 with either STK24 and STK26 kinases and occurs in a Rho-independent manner. Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26. Found in complex with PGCKA1 and members of the STE20 kinases, such as STK24, STK25 and STK26.

Subcellular location. Cytoplasm. Golgi apparatus membrane. Cell membrane.

Tissue specificity. Ubiquitous.

Disease relevance. Cerebral cavernous malformations 3 (CCM3) [MIM:603285] A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM3 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PDCD10 family.

RefSeq proteins (3): NP_009148, NP_665858, NP_665859 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009652	PDCD10	Family
IPR046409	PDC10_dimerisation_sf	Homologous_superfamily
IPR048288	PDCD10_N	Domain

Pfam: PF06840, PF20929

UniProt features (27 total): helix 14, mutagenesis site 6, turn 2, chain 1, modified residue 1, cross-link 1, strand 1, sequence variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
4GEH	X-RAY DIFFRACTION	1.95
3AJM	X-RAY DIFFRACTION	2.3
3W8I	X-RAY DIFFRACTION	2.4
3W8H	X-RAY DIFFRACTION	2.43
3L8I	X-RAY DIFFRACTION	2.5
3RQG	X-RAY DIFFRACTION	2.5
3RQF	X-RAY DIFFRACTION	2.7
3RQE	X-RAY DIFFRACTION	2.8
4TVQ	X-RAY DIFFRACTION	2.8
3L8J	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUL8-F1	90.82	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): 179, 186

Mutagenesis-validated functional residues (6):

Position	Phenotype
132	loss of interaction with ccm2 and pxn; when associated with d-139; d-172 and d-179.
135	loss of interaction with ccm2.
139	loss of interaction with ccm2 and pxn; when associated with d-132; d-172 and d-179.
172	loss of interaction with ccm2 and pxn; when associated with d-132; d-139 and d-179.
175	loss of interaction with ccm2.
179	loss of interaction with ccm2 and pxn; when associated with d-132; d-139 and d-172.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 423 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PEPTIDYL_SERINE_MODIFICATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION

GO Biological Process (24): angiogenesis (GO:0001525), endothelium development (GO:0003158), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of cell migration (GO:0030335), positive regulation of stress-activated MAPK cascade (GO:0032874), positive regulation of peptidyl-serine phosphorylation (GO:0033138), intracellular signal transduction (GO:0035556), intrinsic apoptotic signaling pathway in response to hydrogen peroxide (GO:0036481), negative regulation of apoptotic process (GO:0043066), positive regulation of MAP kinase activity (GO:0043406), wound healing, spreading of cells (GO:0044319), positive regulation of Notch signaling pathway (GO:0045747), regulation of angiogenesis (GO:0045765), protein stabilization (GO:0050821), establishment of Golgi localization (GO:0051683), positive regulation of protein serine/threonine kinase activity (GO:0071902), negative regulation of cell migration involved in sprouting angiogenesis (GO:0090051), Golgi reassembly (GO:0090168), positive regulation of intracellular protein transport (GO:0090316), negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis (GO:1903588), cellular response to leukemia inhibitory factor (GO:1990830), apoptotic process (GO:0006915)

GO Molecular Function (3): protein kinase binding (GO:0019901), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (8): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), FAR/SIN/STRIPAK complex (GO:0090443), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gene expression	2
regulation of gene expression	2
cell migration	2
positive regulation of MAPK cascade	2
intracellular anatomical structure	2
cytoplasm	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
epithelium development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of cell migration	1
positive regulation of cell motility	1
regulation of stress-activated MAPK cascade	1
stress-activated MAPK cascade	1
positive regulation of stress-activated protein kinase signaling cascade	1
positive regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
signal transduction	1
intrinsic apoptotic signaling pathway in response to oxidative stress	1
hydrogen peroxide-mediated programmed cell death	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of protein serine/threonine kinase activity	1
epiboly involved in wound healing	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
positive regulation of signal transduction	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
regulation of protein stability	1

Protein interactions and networks

STRING

1398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDCD10	CCM2	Q9BSQ5	998
PDCD10	STK25	O00506	997
PDCD10	KRIT1	O00522	996
PDCD10	STK26	Q9P289	996
PDCD10	MOB4	Q9Y3A3	982
PDCD10	STK24	Q9Y6E0	977
PDCD10	STRIP1	Q5VSL9	956
PDCD10	STRIP2	Q9ULQ0	942
PDCD10	ITGB1BP1	O14713	919
PDCD10	MAP3K3	Q99759	833
PDCD10	STRN	O43815	785
PDCD10	HEG1	Q9ULI3	773
PDCD10	MAP4K2	Q12851	765
PDCD10	PPP2R1A	P30153	756
PDCD10	RHOA	P06749	725

IntAct

199 interactions, top by confidence:

A	B	Type	Score
PDCD10	STK25	psi-mi:“MI:0915”(physical association)	0.980
STK25	PDCD10	psi-mi:“MI:0915”(physical association)	0.980
PDCD10	STK25	psi-mi:“MI:0914”(association)	0.980
STK25	PDCD10	psi-mi:“MI:0217”(phosphorylation reaction)	0.980
PDCD10	STK25	psi-mi:“MI:0407”(direct interaction)	0.980
KRIT1	CCM2	psi-mi:“MI:0914”(association)	0.960
STK24	PDCD10	psi-mi:“MI:0915”(physical association)	0.950
PDCD10	STK24	psi-mi:“MI:0407”(direct interaction)	0.950

BioGRID (195): PDCD10 (Two-hybrid), PDCD10 (Two-hybrid), STK26 (Two-hybrid), C4orf19 (Two-hybrid), PDCD10 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), PDCD10 (Two-hybrid), PDCD10 (Two-hybrid), PDCD10 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), PDCD10 (Affinity Capture-RNA), CTPS1 (Co-fractionation), HNRNPF (Co-fractionation)

ESM2 similar proteins: A0A1L1QK34, A0A6M3Z554, A5A625, A6UQK9, C6Y4C2, J7H5K9, O08615, P01579, P0C9L0, P0CA45, P0CB24, P0DJE7, P13476, P22917, P41678, P42162, P47055, P63309, P63310, P63311, P84337, P84982, P86853, Q08560, Q10420, Q28ZG0, Q2NHQ2, Q47YC9, Q48864, Q4UKJ5, Q57300, Q57778, Q57915, Q58148, Q5BKH4, Q5I6S9, Q5ZIV5, Q6DF07, Q6NWL1, Q6NX65

Diamond homologs: Q17958, Q5ZIV5, Q6DF07, Q6NWL1, Q6NX65, Q6PHH3, Q8AVR4, Q8VE70, Q9BUL8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PTPN13	down-regulates	PDCD10	dephosphorylation
STK25	unknown	PDCD10	phosphorylation
PTPN13	“down-regulates activity”	PDCD10	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Degradation of beta-catenin by the destruction complex	5	16.3×	1e-03
RHO GTPases Activate Formins	5	7.3×	9e-03
Separation of Sister Chromatids	6	6.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of hippo signaling	7	57.8×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	16
Uncertain significance	58
Likely benign	30
Benign	15

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065419	NM_007217.4(PDCD10):c.333del (p.Lys111fs)	Pathogenic
1075146	NM_007217.4(PDCD10):c.576_579del (p.Ser193fs)	Pathogenic
1075385	NC_000003.11:g.(?167422610)(167437965_?)del	Pathogenic
1075488	NM_007217.4(PDCD10):c.558-2A>G	Pathogenic
1076520	NM_007217.4(PDCD10):c.211dup (p.Ser71fs)	Pathogenic
1326560	NM_007217.4(PDCD10):c.557+1G>A	Pathogenic
1338866	NM_007217.4(PDCD10):c.131dup (p.Arg45fs)	Pathogenic
1358836	NM_007217.4(PDCD10):c.211del (p.Ser71fs)	Pathogenic
1365315	NM_007217.4(PDCD10):c.442_443del (p.Val148fs)	Pathogenic
1379108	NM_007217.4(PDCD10):c.131_132insTT (p.Leu44_Arg45insTer)	Pathogenic
1393706	NM_007217.4(PDCD10):c.522_528del (p.Phe174fs)	Pathogenic
1399974	NM_007217.4(PDCD10):c.160G>T (p.Glu54Ter)	Pathogenic
1430959	NM_007217.4(PDCD10):c.160_161del (p.Glu54fs)	Pathogenic
1453460	NM_007217.4(PDCD10):c.164del (p.Asn55fs)	Pathogenic
1453765	NM_007217.4(PDCD10):c.334_337del (p.Gln112fs)	Pathogenic
1456505	NM_007217.4(PDCD10):c.62_71del (p.Pro21fs)	Pathogenic
1458726	NM_007217.4(PDCD10):c.456T>G (p.Tyr152Ter)	Pathogenic
1459562	NC_000003.11:g.(?167437830)(167437945_?)del	Pathogenic
1460202	NC_000003.11:g.(?167402096)(167405501_?)del	Pathogenic
1460340	NC_000003.11:g.(?167413364)(167437945_?)del	Pathogenic
150113	GRCh38/hg38 3q26.1(chr3:167618839-167688627)x1	Pathogenic
1865	NM_007217.4(PDCD10):c.385C>T (p.Gln129Ter)	Pathogenic
1867	NM_007217.4(PDCD10):c.97_150del	Pathogenic
1869	NM_007217.4(PDCD10):c.475-1G>A	Pathogenic
1870	NC_000003.12:g.(?167683298(167734892_?)del	Pathogenic
2023706	NM_007217.4(PDCD10):c.274_275del (p.Met92fs)	Pathogenic
2115676	NM_007217.4(PDCD10):c.97-1G>A	Pathogenic
2124205	NM_007217.4(PDCD10):c.557+1G>T	Pathogenic
2427340	NC_000003.11:g.(?167413364)(167413530_?)del	Pathogenic
2427341	NC_000003.11:g.(?167405002)(167413530_?)del	Pathogenic

SpliceAI

1871 predictions. Top by Δscore:

Variant	Effect	Δscore
3:167684385:TTGCC:T	acceptor_gain	1.0000
3:167684387:GCCC:G	acceptor_loss	1.0000
3:167684388:CC:C	acceptor_gain	1.0000
3:167684388:CCCTG:C	acceptor_loss	1.0000
3:167684389:CC:C	acceptor_gain	1.0000
3:167684389:CCTGT:C	acceptor_loss	1.0000
3:167684390:C:CA	acceptor_loss	1.0000
3:167684390:C:CC	acceptor_gain	1.0000
3:167684391:T:A	acceptor_loss	1.0000
3:167687232:A:AC	donor_gain	1.0000
3:167687233:C:CC	donor_gain	1.0000
3:167687613:AC:A	donor_gain	1.0000
3:167687614:CC:C	donor_gain	1.0000
3:167687614:CCCTG:C	donor_gain	1.0000
3:167687692:CC:C	acceptor_gain	1.0000
3:167687693:CC:C	acceptor_gain	1.0000
3:167695594:A:AC	donor_gain	1.0000
3:167695595:C:CC	donor_gain	1.0000
3:167695719:TACT:T	acceptor_gain	1.0000
3:167695721:CT:C	acceptor_gain	1.0000
3:167695723:C:CC	acceptor_gain	1.0000
3:167697003:CGTTA:C	donor_loss	1.0000
3:167697004:GTTA:G	donor_loss	1.0000
3:167697005:TTACC:T	donor_loss	1.0000
3:167697006:TAC:T	donor_loss	1.0000
3:167697007:A:C	donor_loss	1.0000
3:167697008:CCTTC:C	donor_loss	1.0000
3:167697123:CAGC:C	acceptor_gain	1.0000
3:167697125:GCCTA:G	acceptor_loss	1.0000
3:167697126:CCTA:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003342 (3:167735447 G>C), RS1000005256 (3:167692719 C>A,G), RS1000076429 (3:167734526 G>A,C), RS1000095374 (3:167728812 C>T), RS1000105804 (3:167725225 C>T), RS1000192457 (3:167701009 C>A), RS1000239066 (3:167700643 C>A), RS1000343262 (3:167687212 A>G), RS1000362797 (3:167722518 T>G), RS1000371408 (3:167716264 G>A), RS1000450247 (3:167694258 T>A), RS1000539649 (3:167725503 T>C), RS1000539979 (3:167714143 A>C), RS1000601738 (3:167709430 G>A), RS1000668518 (3:167708066 C>T)

Disease associations

OMIM: gene MIM:609118 | disease phenotypes: MIM:603285, MIM:116860, MIM:604218, MIM:108010

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebral cavernous malformation 3	Definitive	Autosomal dominant
famililal cerebral cavernous malformations	Supportive	Autosomal dominant

Mondo (7): cerebral cavernous malformation 3 (MONDO:0011305), cerebral cavernous malformation 1 (MONDO:0020724), familial encephalopathy with neuroserpin inclusion bodies (MONDO:0011412), cerebral cavernous malformation (MONDO:0000820), cavernous hemangioma (MONDO:0003155), arteriovenous malformations of the brain (MONDO:0007154), famililal cerebral cavernous malformations (MONDO:0031037)

Orphanet (4): Familial cerebral cavernous malformation (Orphanet:221061), Familial encephalopathy with neuroserpin inclusion bodies (Orphanet:85110), Brain arteriovenous malformation (Orphanet:46724), NON RARE IN EUROPE: Cerebral cavernous malformations (Orphanet:164)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000951	Abnormality of the skin
HP:0001028	Hemangioma
HP:0001048	Cavernous hemangioma
HP:0001250	Seizure
HP:0001324	Muscle weakness
HP:0001342	Cerebral hemorrhage
HP:0002170	Intracranial hemorrhage
HP:0002315	Headache
HP:0002514	Cerebral calcification
HP:0002516	Increased intracranial pressure
HP:0002572	Episodic vomiting
HP:0002650	Scoliosis
HP:0002858	Meningioma
HP:0003011	Abnormality of the musculature
HP:0003401	Paresthesia
HP:0003470	Paralysis
HP:0003621	Juvenile onset
HP:0003829	Typified by incomplete penetrance
HP:0006576	Hepatic vascular malformations
HP:0007797	Developmental retinal vascular malformation
HP:0007872	Choroidal hemangioma
HP:0009588	Vestibular schwannoma
HP:0009592	Astrocytoma
HP:0010512	Adrenal calcification
HP:0011276	Vascular skin abnormality
HP:0011513	Retinal cavernous hemangioma
HP:0012721	Venous malformation
HP:0012748	Focal T2 hyperintense brainstem lesion
HP:0012749	Focal T2 hypointense brainstem lesion

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004048_1	Fast beta electroencephalogram	5.000000e-09
GCST90002402_656	Platelet count	1.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0004309	platelet count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D006392	Hemangioma, Cavernous	C04.557.645.375.385; C10.228.140.232.625; C14.907.454.385; C15.378.463.515.385
D002538	Intracranial Arteriovenous Malformations	C10.228.140.300.520; C10.500.190.500; C14.240.850.750.295; C14.240.850.875.500; C14.907.150.295; C14.907.253.560.400; C16.131.240.850.750.295; C16.131.240.850.875.500; C16.131.666.190.500
C566393	Cerebral Cavernous Malformations 3 (supp.)
C536841	Familial encephalopathy with neuroserpin inclusion bodies (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066262 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.67	Kd	2.146	nM	CHEMBL3752910
8.67	ED50	2.146	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2148951: Binding affinity to human PDCD10 incubated for 45 mins by Kinobead based pull down assay	kd	0.0021	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Air Pollutants	decreases expression, increases abundance	2
Arsenic	affects methylation, affects response to substance	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
caffeic acid	decreases expression, increases reaction	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
4-methoxycinnamate methyl ester	decreases expression, increases reaction	1
10’(Z),13’(E),15’(E)-heptadecatrienylhydroquinone	increases expression	1
jinfukang	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Amiodarone	increases expression	1
Aspirin	increases expression	1
Drugs, Chinese Herbal	decreases expression, increases reaction	1
Ivermectin	decreases expression	1
Mustard Gas	affects expression, affects reaction	1
Plant Extracts	affects cotreatment, increases expression	1
Valproic Acid	affects 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
CHEMBL5651993	Binding	Binding affinity to human PDCD10 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

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2A5	Abcam HeLa PDCD10 KO	Cancer cell line	Female
CVCL_D9ME	Ubigene HEK293 PDCD10 KO	Transformed cell line	Female
CVCL_TC58	HAP1 PDCD10 (-) 1	Cancer cell line	Male
CVCL_XR44	HAP1 PDCD10 (-) 2	Cancer cell line	Male
CVCL_ZD03	Mel 04.01	Cancer cell line	Male
CVCL_ZD06	Mel 12.07	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01758211	PHASE3	UNKNOWN	Functional Magnetic Resonance Imagine(fMRI)Navigation in Intracranial Arteriovenous Malformation Surgery
NCT03474614	PHASE2	TERMINATED	Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation
NCT03589014	PHASE2	COMPLETED	Treat_CCM: Propranolol in Familial Cerebral Cavernous Malformation
NCT05085561	PHASE2	COMPLETED	The Symptomatic Cerebral Cavernous Malformation Trial of REC-994
NCT04297033	PHASE2	UNKNOWN	Lovastatin for Treatment of Brain Arteriovenous Malformations
NCT00783523	PHASE1	COMPLETED	Influence of MMP on Brain AVM Hemorrhage
NCT02314377	PHASE1	COMPLETED	Bevacizumab Therapy for Brain Arteriovenous Malformation
NCT03652181	Not specified	COMPLETED	CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness
NCT01764451	EARLY_PHASE1	TERMINATED	Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins
NCT01764529	Not specified	ACTIVE_NOT_RECRUITING	Modifiers of Disease Severity in Cerebral Cavernous Malformations
NCT03467295	Not specified	UNKNOWN	Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in CHina.
NCT06983132	Not specified	RECRUITING	Natural History of Familial Cerebral Cavernous Malformations: the CCM_Italia Cohort Study
NCT00916903	Not specified	TERMINATED	Genetic Disease Gene Identification
NCT02603328	PHASE1/PHASE2	COMPLETED	Atorvastatin Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial
NCT02946866	Not specified	UNKNOWN	CoHOrt of Cerebral CavernOus maLformATion: multicEnter Prospective Observational Study
NCT04467489	Not specified	ACTIVE_NOT_RECRUITING	Biomarkers of CASH
NCT05148663	Not specified	TERMINATED	CCM Blood Biomarker Validation Study
NCT05298709	Not specified	TERMINATED	Functional Magnetic Resonance Imaging (fMRI) Vascular Reactivity in Cerebral Cavernous Malformations (CCM)
NCT04076449	Not specified	RECRUITING	Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation Related Epilepsy
NCT05477680	Not specified	RECRUITING	Intraoperative Brain Shift Calculation Study
NCT05484219	Not specified	SUSPENDED	Functional Navigation in Surgery of Cerebral Tumors and Vascular Malformations
NCT05484245	Not specified	RECRUITING	Sonography-guided Resection of Brain Mass Lesions
NCT06724029	Not specified	RECRUITING	Neurosurgical Outcome Network
NCT06915649	Not specified	RECRUITING	Exploration and Evaluation of Amygdalo-Hippocampectomy According to Prof. Coubes’ Technique: An Anatomical, Clinical, and Educational Approach
NCT01689402	Not specified	COMPLETED	MRI for the Early Evaluation of Acute Intracerebral Hemorrhage
NCT01803685	Not specified	UNKNOWN	Nationwide Treatment Survey of Intracranial Arteriovenous Malformation in China
NCT02085278	Not specified	COMPLETED	Safety of Apollo Micro Catheter in Pediatric Patients
NCT02180958	Not specified	COMPLETED	Evaluation of ONYX in ENDOVASCULAR Treatment of Cerebral AVMs
NCT02602990	Not specified	COMPLETED	Treatment of Cerebral Arteriovenous Malformations With SQUID™ Liquid Embolic Agent
NCT02868008	Not specified	UNKNOWN	Multimodal Imaging Techniques in Assessing the Surgical Risk for Eloquent Arteriovenous Malformations
NCT03209804	Not specified	COMPLETED	Surgical Management of Cerebral Arteriovenous Malformations Within Hybrid Operation Room
NCT03367975	Not specified	UNKNOWN	NIRS Monitoring During Intracranial Interventions
NCT03413852	Not specified	UNKNOWN	Treatment of Cerebral Arteriovenous Malformations With SQUID Liquid Embolic Agent (CHOICE)
NCT03676868	Not specified	RECRUITING	Biology of Cerebral Arteriovenous Malformations and Prognosis of Cerebral Arteriovenous Malformations
NCT03731000	Not specified	RECRUITING	PHIL® Embolic System Pediatric IDE
NCT03995823	Not specified	COMPLETED	Evaluation of Nidus Occlusion After Gamma Knife Radiosurgery of Cerebral Arteriovenous Malformations Using Magnetic Resonance Imaging
NCT04328181	Not specified	UNKNOWN	Comparison of Imaging Quality Between Spectral Photon Counting Computed Tomography (SPCCT) and Dual Energy Computed Tomography (DECT)
NCT04553549	Not specified	COMPLETED	Safety and Feasibility of the Infinity Catheter for Radial Access
NCT04572568	Not specified	RECRUITING	Registry of Multimodality Treatment for Brain Arteriovenous Malformation in Mainland China
NCT04593966	Not specified	UNKNOWN	Pediatric and Adult Cerebral Arteriovenous Malformation Neurofunctional Outcomes