PDCD10

Chr 3AD

programmed cell death 10

Also known as: CCM3, TFAR15

The PDCD10 protein regulates cell proliferation and apoptosis, modulates MAPK signaling pathways, and is essential for normal vascular development and angiogenesis. Mutations cause cerebral cavernous malformations-3, which are vascular malformations that lead to seizures and cerebral hemorrhages, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants, indicating that protein function is critical for normal development.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Cerebral cavernous malformations-3MIM #603285
AD
0
Active trials
18
Pubs (1 yr)
163
P/LP submissions
1%
P/LP missense
0.33
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryPDCD10
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
120 unique Pathogenic / Likely Pathogenic· 64 VUS of 253 total submissions
📖
GeneReview available — PDCD10
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.962
Z-score 3.30
OE 0.07 (0.020.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.43Z-score
OE missense 0.63 (0.520.76)
74 obs / 117.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.020.33)
00.351.4
Missense OE0.63 (0.520.76)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 1 / 14.6Missense obs/exp: 74 / 117.8Syn Z: 0.31

ClinVar Variant Classifications

253 submitted variants in ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic24
VUS64
Likely Benign31
Benign18
Conflicting2
96
Pathogenic
24
Likely Pathogenic
64
VUS
31
Likely Benign
18
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
46
0
50
0
96
Likely Pathogenic
14
1
9
0
24
VUS
0
34
29
1
64
Likely Benign
0
1
11
19
31
Benign
0
0
18
0
18
Conflicting
2
Total603611720235

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PDCD10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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