KDELR3

Chr 22

KDEL endoplasmic reticulum protein retention receptor 3

Also known as: ERD23, ERD2L3

NCBI Gene: 11015ENSG00000100196UniProt: O43731

This gene encodes a member of the KDEL endoplasmic reticulum protein retention receptor family. Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continual retrieval from the cis-Golgi, or a pre-Golgi compartment. Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, usually lys-asp-glu-leu (KDEL) in animal cells, and his-asp-glu-leu (HDEL) in S. cerevisiae. This process is mediated by a receptor that recognizes, and binds the tetrapeptide-containing protein, and returns it to the ER. In yeast, the sorting receptor encoded by a single gene, ERD2, is a seven-transmembrane protein. Unlike yeast, several human homologs of the ERD2 gene, constituting the KDEL receptor gene family, have been described. KDELR3 was the third member of the family to be identified. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

67
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KDELR3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 32 VUS of 67 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.
1.94LOEUF
pLI 0.000
Z-score -1.51
OE 1.56 (0.98–1.94)
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.
-0.22Z-score
OE missense 1.06 (0.91–1.23)
123 obs / 116.3 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.1.56 (0.98–1.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.91–1.23)
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.1.14
0≤1.21.6
LoF obs/exp: 13 / 8.3Missense obs/exp: 123 / 116.3Syn Z: -0.74

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS32
Likely Benign1
Benign1
Conflicting1
19
Pathogenic
3
Likely Pathogenic
32
VUS
1
Likely Benign
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
3
0
3
VUS
0
30
2
0
32
Likely Benign
0
1
0
0
1
Benign
1
0
0
0
1
Conflicting
—1
Total13124057

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

View in ClinVar →

Protein Context — Lollipop Plot

KDELR3 · 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
Exome-wide association study identifies KDELR3 mutations in extreme myopia.
Yuan J et al.·Nat Commun
2024
KDELR3 overexpression as a novel prognostic and diagnostic biomarker in glioma: comprehensive bioinformatic analysis insights.
Feng J et al.·Sci Rep
2024
KDELR3 Is a Prognostic Biomarker Related to the Immune Infiltration and Chemoresistance of Anticancer Drugs in Uveal Melanoma.
Zhang J et al.·Dis Markers
2022
Screening potential diagnostic biomarkers for PLA2R‑associated idiopathic membranous nephropathy by WGCNA analysis and LASSO algorithm.
Huang J et al.·Ren Fail
2025
Melanoblast transcriptome analysis reveals pathways promoting melanoma metastasis.
Marie KL et al.·Nat Commun
2020
Endoplasmic reticulum stress regulators exhibit different prognostic, therapeutic and immune landscapes in pancreatic adenocarcinoma.
Liu S et al.·J Cell Mol Med
2024
Identification of four-gene signature to diagnose osteoarthritis through bioinformatics and machine learning methods.
Chen Z et al.·Cytokine
2023
PSAT1 enhances the efficacy of the prognosis estimation nomogram model in stage-based clear cell renal cell carcinoma.
Wang J et al.·BMC Cancer
2024Functional
Exploring the potential biological significance of KDELR family genes in lung adenocarcinoma.
Li P et al.·Sci Rep
2024
Gene signature based on glycolysis is closely related to immune infiltration of patients with osteoarthritis.
Chen Z et al.·Cytokine
2023Cohort
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