DERL3

Chr 22

derlin 3

Also known as: C22orf14, IZP6, LLN2, derlin-3

NCBI Gene: 91319ENSG00000099958UniProt: Q96Q80

The protein encoded by this gene belongs to the derlin family, and resides in the endoplasmic reticulum (ER). Proteins that are unfolded or misfolded in the ER must be refolded or degraded to maintain the homeostasis of the ER. This protein appears to be involved in the degradation of misfolded glycoproteins in the ER. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Oct 2008]

187
ClinVar variants
60
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DERL3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
60 Pathogenic / Likely Pathogenic· 100 VUS of 187 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.
1.24LOEUF
pLI 0.000
Z-score 1.03
OE 0.66 (0.37–1.24)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.17Z-score
OE missense 1.04 (0.91–1.19)
148 obs / 142.4 exp
Tolerant

Tolerant to missense variation

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.0.66 (0.37–1.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.91–1.19)
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.1.15
0≤1.21.6
LoF obs/exp: 7 / 10.6Missense obs/exp: 148 / 142.4Syn Z: -0.92

ClinVar Variant Classifications

187 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic49
Likely Pathogenic11
VUS100
Likely Benign8
Benign3
Conflicting2
49
Pathogenic
11
Likely Pathogenic
100
VUS
8
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
0
0
11
0
11
VUS
0
33
67
0
100
Likely Benign
0
1
3
4
8
Benign
0
0
3
0
3
Conflicting
—2
Total0341334173

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

View in ClinVar →

Protein Context — Lollipop Plot

DERL3 · 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
KAT3B-mediated succinylation of DERL3 suppresses osteogenic differentiation by promoting M1/M2 macrophage polarization.
Yu B et al.·Biochem Pharmacol
2025
Integrated profiling of endoplasmic reticulum stress-related DERL3 in the prognostic and immune features of lung adenocarcinoma.
Lin L et al.·Front Immunol
2022
DERL3 suppresses colorectal cancer metastasis through negatively regulating MYCN level.
Yu F et al.·Minerva Med
2023
Overexpression of Derlin 3 is associated with malignant phenotype of breast cancer cells.
Shibata M et al.·Oncol Rep
2017
DERL3 functions as a tumor suppressor in gastric cancer.
Li Y et al.·Comput Biol Chem
2020
Target Fibroblast-B cell crosstalk via MIF signaling drives pathogenic B cell differentiation and joint damage in knee osteoarthritis.
Tu B et al.·Inflamm Res
2025
Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes.
Li F et al.·Sci Rep
2022Functional
Systematic Construction and Validation of a Novel Ferroptosis-Related Gene Model for Predicting Prognosis in Cervical Cancer.
Qin W et al.·J Immunol Res
2022Functional
Identification and validation of prognostic genes and prognostic models associated with cutaneous melanoma and integrative stress response.
Zhang Z et al.·Front Immunol
2025Functional
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