PDCD6

Chr 5

programmed cell death 6

Also known as: ALG-2, ALG2, PEF1B

NCBI Gene: 10016ENSG00000249915UniProt: O75340

This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]

192
ClinVar variants
132
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— PDCD6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
132 Pathogenic / Likely Pathogenic· 51 VUS of 192 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.009
Z-score 1.70
OE 0.45 (0.23–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.45Z-score
OE missense 0.89 (0.76–1.04)
111 obs / 125.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.23–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.76–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 5 / 11.1Missense obs/exp: 111 / 125.3Syn Z: 0.15

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic130
Likely Pathogenic2
VUS51
Likely Benign6
Benign3
130
Pathogenic
2
Likely Pathogenic
51
VUS
6
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
130
0
130
Likely Pathogenic
0
0
2
0
2
VUS
0
26
25
0
51
Likely Benign
0
0
5
1
6
Benign
0
0
3
0
3
Total0261651192

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

View in ClinVar →

Protein Context — Lollipop Plot

PDCD6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Contribution of PDCD6 Polymorphisms to Oral Cancer Risk.
Shih LC et al.·Cancer Genomics Proteomics
2022
Rare-variant association analysis reveals known and new age-related hearing loss genes.
Cornejo-Sanchez DM et al.·Eur J Hum Genet
2023
PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation.
Wang X et al.·J Exp Clin Cancer Res
2020
Machine learning-based analysis of programmed cell death types and key genes in intervertebral disc degeneration.
Lv Y et al.·Apoptosis
2025
PDCD6 is an independent predictor of progression free survival in epithelial ovarian cancer.
Su D et al.·J Transl Med
2012
MicroRNA-183 promotes cell proliferation via regulating programmed cell death 6 in pediatric acute myeloid leukemia.
Wang X et al.·J Cancer Res Clin Oncol
2017
Structural basis of Sorcin-mediated calcium-dependent signal transduction.
Ilari A et al.·Sci Rep
2015
Identification of prognostic biomarkers in gastric cancer using endoscopic biopsy samples.
Yamada Y et al.·Cancer Sci
2008Clinical trial
Association of two selected polymorphisms with developed endometriosis in women from Slovakia.
Pitonak J et al.·Bratisl Lek Listy
2016
Proteomic analysis of proton beam irradiated human melanoma cells.
Kedracka-Krok S et al.·PLoS One
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools