KDELR2

Chr 7

KDEL endoplasmic reticulum protein retention receptor 2

Also known as: ELP-1, ERD2.2, OI21

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. KDELR2 was the second member of the family to be identified, and it encodes a protein which is 83% identical to the KDELR1 gene product. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.74
Clinical SummaryKDELR2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
4 unique Pathogenic / Likely Pathogenic· 27 VUS of 48 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.74LOEUF
pLI 0.167
Z-score 2.15
OE 0.29 (0.130.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.80Z-score
OE missense 0.79 (0.670.94)
91 obs / 115.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.29 (0.130.74)
00.351.4
Missense OE?0.79 (0.670.94)
00.61.4
Synonymous OE?1.04
01.21.6
LoF obs/exp: 3 / 10.5Missense obs/exp: 91 / 115.3Syn Z: -0.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongKDELR2-related osteogenesis imperfectaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.83top 10%
GOF
0.77top 25%
LOF
0.2483th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

48 submitted variants in ClinVar

Classification Summary

Pathogenic4
VUS27
Likely Benign4
Benign4
Conflicting2
4
Pathogenic
27
VUS
4
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
0
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
27
0
0
27
Likely Benign
0
1
1
2
4
Benign
0
0
3
1
4
Conflicting
2
Total2304341

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 52) ClinVar copy-number / structural variants overlap KDELR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

KDELR2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →