KDELR2
protein-codingKDEL endoplasmic reticulum protein retention receptor 2, the group of KDEL endoplasmic reticulum protein retention receptors
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030861
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0030861
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0030861
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KDELR2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006854.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 3 | 4 | |||
| missense | 2 | 2 | 28 | 32 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 4 | 2 | 29 | 3 | 0 | 38 |
Highest pathogenic variant AF is 0.000008673801
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006845.1 | 5 | MANE Select | |
| Ensembl | ENSP00000258739.4 | 5 | MANE Select | |
| RefSeq | NP_001094073.1 | 4 | Standard | |
| Ensembl | ENSP00000371702.3 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vibrio cholerae infection - Homo sapiens (human)
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- protein retention in ER lumen
- intracellular protein transport
- endoplasmic reticulum to Golgi vesicle-mediated transport
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
Molecular Function
- KDEL sequence binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- Golgi apparatus
- cis-Golgi network
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000258739
- Coding exons
- 5
- Length
- 38290
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125747
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.804 | 91 | 115 | 0.789 | 0.00000605 | 1356 |
| Missense (PolyPhen) | 13 | 27.735 | 0.46873 | 301 | ||
| Synonymous | -0.195 | 51 | 49.3 | 1.04 | 0.00000275 | 435 |
| Loss of Function | 2.15 | 3 | 10.5 | 0.285 | 5.32e-7 | 117 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for the retention of luminal endoplasmic reticulum proteins. Determines the specificity of the luminal ER protein retention system. Also required for normal vesicular traffic through the Golgi. This receptor recognizes K-D-E-L.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.283
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.838
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |