GeneBe

PDCD10

protein-coding

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

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:
  • CCM3

MANE transcript

NM_007217.4

Inheritance

AD

ClinVar variants

P:90U:45B:21

Top phenotype

Cerebral cavernous malformations 3

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr3:167,683,298-167,734,939

External References & Databases

Ensembl (ENSG00000114209)NCBI Gene (11235)OMIM (609118)HGNC:8761GenCCUniProt (Q9BUL8)AlphaFoldClinVar (PDCD10)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~51.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebral cavernous malformation 3DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011305

Submitter: G2P

famililal cerebral cavernous malformationsSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0031037

Submitter: Orphanet

cerebral cavernous malformation 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011305

Submitter: Labcorp Genetics (formerly Invitae)

cerebral cavernous malformation 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011305

Submitter: Genomics England PanelApp

cerebral cavernous malformation 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011305

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cerebral cavernous malformations 3AD

Manifestation: Cardiovascular; Neurologic

Intervention: Cardiovascular; Neurologic; Pharmacogenomic

Rationale: 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)

Refs: 15543491; 16380626; 18060436; 19088123; 20301470; 21029238; 23485406; 23595507; 23663874Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDCD10 variants in ClinVar

12 Conditions Cataloged
Cerebral cavernous malformation 3Total: 121
not providedTotal: 52
Inborn genetic diseasesTotal: 29
PDCD10-related disorderTotal: 23
not specifiedTotal: 8
Cerebral cavernous malformationTotal: 3
HemiparesisTotal: 1
Cerebral cavernous malformation 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007217.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
19
clinvar
 20
missense
1
clinvar
39
clinvar
2
clinvar
 42
nonsense
14
clinvar
5
clinvar
1
clinvar
 20
start loss
0
frameshift
34
clinvar
14
clinvar
 48
splice donor/acceptor (+/-2bp)
13
clinvar
9
clinvar
4
clinvar
 26
Total612945210156

Highest pathogenic variant AF is 0.0000065765244

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 111 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_007217.4RefSeqNP_009148.27MANE Select
ENST00000392750.7EnsemblENSP00000376506.27MANE Select
NM_001439202.1RefSeqNP_001426131.17Standard
NM_001439204.1RefSeqNP_001426133.17Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
pdcd10bDanio rerio

Structure: whole organism

Quality: dead

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Validated targets of C-MYC transcriptional activation

Biological Process

  • angiogenesis
  • positive regulation of cell population proliferation
  • positive regulation of gene expression
  • negative regulation of gene expression
  • positive regulation of cell migration

Molecular Function

  • protein binding
  • protein kinase binding
  • protein homodimerization activity
  • protein N-terminus binding

Cellular Component

  • Golgi membrane
  • cytoplasm
  • Golgi apparatus
  • cytosol
  • plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000392750
Coding exons
7
Length
51642
Individuals with no LoFs
123959
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
123960
p
0.00000403
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.43741180.6280.000006161426
Missense (PolyPhen)1127.1850.40464372
Synonymous0.3103739.50.9370.00000222370
Loss of Function3.30114.60.06859.98e-7146

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.124

Intolerance Scores

RVIS EVS
-0.03
RVIS percentile EVS
51.04

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.942

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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