PDCD10

programmed cell death 10, the group of CCM adhesion complex|STRIPAK complex

Basic information

Region (hg38): 3:167683298-167734939

Previous symbols: [ "CCM3" ]

Links

ENSG00000114209 ∙ NCBI:11235 ∙ OMIM:609118 ∙ HGNC:8761 ∙ Uniprot:Q9BUL8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebral cavernous malformation 3 (Strong), mode of inheritance: AD
• cerebral cavernous malformation 3 (Strong), mode of inheritance: AD
• famililal cerebral cavernous malformations (Supportive), mode of inheritance: AD
• cerebral cavernous malformation 3 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebral cavernous malformations 3	AD	Cardiovascular; Neurologic; Pharmacogenomic	Surveillance measures (eg, spinal cord MRI, annual brain gradient echo or susceptibility-weighted imaging) has been advocated; Agents that increase risk of hemorrhage should be avoided (eg, aspirin, NSAIDs, heparin, warfarin)	Cardiovascular; Neurologic	15543491; 16380626; 18060436; 19088123; 20301470; 21029238; 23485406; 23595507; 23663874

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDCD10 gene.

• Cerebral cavernous malformation 3 (42 variants)
• not provided (11 variants)
• Cerebral cavernous malformation 1 (1 variants)
• Cerebral cavernous malformation (1 variants)
• PDCD10-related disorder (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDCD10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10		10
missense		1	21	1		23
nonsense	11	4				15
start loss						0
frameshift	26	5				31
inframe indel			3			3
splice donor/acceptor (+/-2bp)	10	7				17
splice region	2	1	6	4		13
non coding			11	7	16	34
Total	47	17	35	18	16

Highest pathogenic variant AF is 0.00000658

Variants in PDCD10

This is a list of pathogenic ClinVar variants found in the PDCD10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-167683969-C-T		Cerebral cavernous malformation 3	Uncertain significance (Jan 13, 2018)
3-167684023-C-A		Cerebral cavernous malformation 3	Likely benign (Jan 13, 2018)
3-167684087-A-G		Cerebral cavernous malformation 3	Uncertain significance (Jan 13, 2018)
3-167684109-T-G		Cerebral cavernous malformation 3	Uncertain significance (Jan 12, 2018)
3-167684134-G-A		Cerebral cavernous malformation 3	Uncertain significance (Jan 12, 2018)
3-167684167-G-A		Cerebral cavernous malformation 3	Uncertain significance (Jan 12, 2018)
3-167684169-T-C		Cerebral cavernous malformation 3	Uncertain significance (Jan 12, 2018)
3-167684221-T-A		Cerebral cavernous malformation 3	Uncertain significance (Jan 13, 2018)
3-167684245-A-G		Cerebral cavernous malformation 3	Uncertain significance (Jan 12, 2018)
3-167684313-C-A			Uncertain significance (Oct 04, 2013)
3-167684317-A-G		Inborn genetic diseases	Likely benign (Apr 01, 2022)
3-167684349-G-A			Likely pathogenic (Dec 07, 2022)
3-167684354-A-AT		Cerebral cavernous malformation 3	Pathogenic (Nov 18, 2023)
3-167684361-G-A		Cerebral cavernous malformation 3	Pathogenic (Oct 13, 2023)
3-167684362-G-GT		Cerebral cavernous malformation 3	Pathogenic/Likely pathogenic (Jan 23, 2023)
3-167684367-CACTT-C		Cerebral cavernous malformation 3	Pathogenic (Mar 26, 2020)
3-167684371-T-TA		Cerebral cavernous malformation 3 • Cerebral cavernous malformation	Pathogenic/Likely pathogenic (Oct 06, 2021)
3-167684373-C-T		Cerebral cavernous malformation • Cerebral cavernous malformation 3 • PDCD10-related disorder	Conflicting classifications of pathogenicity (Jul 17, 2023)
3-167684374-G-A		Cerebral cavernous malformation 3	Likely benign (Oct 03, 2023)
3-167684376-A-T		Inborn genetic diseases	Uncertain significance (Apr 24, 2023)
3-167684380-ATT-A		Cerebral cavernous malformation 3	Pathogenic (Nov 04, 2019)
3-167684391-T-A			Likely pathogenic (Apr 25, 2016)
3-167684391-T-C		Cerebral cavernous malformation 3	Pathogenic (Aug 04, 2020)
3-167684391-T-G		Cerebral cavernous malformation 3	Pathogenic (Aug 05, 2020)
3-167684448-T-C			Benign (Mar 03, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDCD10	protein_coding	protein_coding	ENST00000392750	7	51642

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.962	0.0380	123959	0	1	123960	0.00000403

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	74	118	0.628	0.00000616	1426
Missense in Polyphen		11	27.185	0.40464		372
Synonymous	0.310	37	39.5	0.937	0.00000222	370
Loss of Function	3.30	1	14.6	0.0685	9.98e-7	146

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and STK26 activity (PubMed:27807006). Important for cell migration, and for normal structure and assembly of the Golgi complex (PubMed:27807006). 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 (By similarity). {ECO:0000250|UniProtKB:Q8VE70, ECO:0000269|PubMed:15543491, ECO:0000269|PubMed:17360971, ECO:0000269|PubMed:20332113, ECO:0000269|PubMed:27807006}.
• Pathway: Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.761
• hipred: Y
• hipred_score: 0.768
• ghis: 0.679

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pdcd10
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: pdcd10b
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: dead

Gene ontology

• Biological process: angiogenesis;positive regulation of cell population proliferation;positive regulation of gene expression;negative regulation of gene expression;positive regulation of cell migration;positive regulation of stress-activated MAPK cascade;positive regulation of peptidyl-serine phosphorylation;regulation of Rho protein signal transduction;intrinsic apoptotic signaling pathway in response to hydrogen peroxide;response to hydrogen peroxide;negative regulation of apoptotic process;stress fiber assembly;positive regulation of MAP kinase activity;wound healing, spreading of cells;positive regulation of Notch signaling pathway;protein stabilization;establishment of Golgi localization;positive regulation of protein serine/threonine kinase activity;negative regulation of cell migration involved in sprouting angiogenesis;Golgi reassembly;positive regulation of intracellular protein transport;negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis;cellular response to leukemia inhibitory factor
• Cellular component: Golgi membrane;cytoplasm;Golgi apparatus;cytosol;plasma membrane;extracellular exosome
• Molecular function: protein binding;protein kinase binding;protein homodimerization activity;protein N-terminus binding