KDELR3

Chr 22

KDEL endoplasmic reticulum protein retention receptor 3

Also known as: ERD23, ERD2L3

The protein functions as a receptor that recognizes the KDEL sequence motif on endoplasmic reticulum resident proteins and mediates their retrieval from the Golgi apparatus back to the endoplasmic reticulum. Mutations in KDELR3 cause neurodevelopmental disorders with intellectual disability, seizures, and distinctive facial features, following an autosomal recessive inheritance pattern. The gene shows extremely low constraint against loss-of-function variants, suggesting tolerance to protein disruption in the general population.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.94
Clinical SummaryKDELR3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.94LOEUF
pLI 0.000
Z-score -1.51
OE 1.56 (0.981.94)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.06 (0.911.23)
123 obs / 116.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.56 (0.981.94)
00.351.4
Missense OE1.06 (0.911.23)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 13 / 8.3Missense obs/exp: 123 / 116.3Syn Z: -0.74
DN
0.75top 25%
GOF
0.6346th %ile
LOF
0.3455th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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