DERL2

Chr 17

derlin 2

Also known as: CGI-101, DERtrin-2, F-LAN-1, F-LANa, FLANa, derlin-2

NCBI Gene: 51009ENSG00000072849UniProt: Q9GZP9

Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be refolded or degraded to maintain the homeostasis of the ER. DERL2 is involved in the degradation of misfolded glycoproteins in the ER (Oda et al., 2006 [PubMed 16449189]).[supplied by OMIM, Mar 2008]

46
ClinVar variants
22
Pathogenic / LP
0.96
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DERL2
⚡
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
22 Pathogenic / Likely Pathogenic· 23 VUS of 46 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.33LOEUF
pLI 0.957
Z-score 3.26
OE 0.07 (0.02–0.33)
Highly constrained

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

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.
1.62Z-score
OE missense 0.60 (0.50–0.73)
79 obs / 131.1 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.0.07 (0.02–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.60 (0.50–0.73)
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.1.19
0≤1.21.6
LoF obs/exp: 1 / 14.3Missense obs/exp: 79 / 131.1Syn Z: -1.05

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS23
Likely Benign1
21
Pathogenic
1
Likely Pathogenic
23
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
15
8
0
23
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total01530146

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

View in ClinVar →

Protein Context — Lollipop Plot

DERL2 · 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
Clinical and Biological Significance of Sodium Channel Modifier 1 as a Component of the Minor Spliceosome in Hepatocellular Carcinoma.
Ofuchi T et al.·Ann Surg Oncol
2025
Exploring Lead loci shared between schizophrenia and Cardiometabolic traits.
He Q et al.·BMC Genomics
2022
A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death.
Ma H et al.·Cell Rep
2015
Upregulation of FAM134B inhibits endoplasmic reticulum stress-related degradation protein expression and promotes hepatocellular carcinogenesis.
Wang H et al.·J Cell Mol Med
2024
Interactions between the ROP18 kinase and host cell proteins that aid in the parasitism of Toxoplasma gondii.
Cheng L et al.·Acta Trop
2012
Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma.
Finalet Ferreiro J 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