KDELR2

KDEL endoplasmic reticulum protein retention receptor 2, the group of KDEL endoplasmic reticulum protein retention receptors

Basic information

Region (hg38): 7:6445952-6484190

Links

ENSG00000136240 ∙ NCBI:11014 ∙ OMIM:609024 ∙ HGNC:6305 ∙ Uniprot:P33947 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta (Supportive), mode of inheritance: AD
• osteogenesis imperfecta, type 21 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type XXI	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	Musculoskeletal	33053334; 33964184

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDELR2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDELR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			15	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	1	2
Total	0	0	15	2	2

Variants in KDELR2

This is a list of pathogenic ClinVar variants found in the KDELR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-6445973-A-T		not specified	Uncertain significance (Nov 18, 2022)
7-6446013-T-C		not specified	Uncertain significance (Feb 06, 2024)
7-6446081-T-C		not specified	Uncertain significance (Feb 28, 2024)
7-6447809-C-T		not specified	Uncertain significance (Jan 02, 2024)
7-6447827-G-C		not specified	Uncertain significance (Oct 25, 2023)
7-6462962-TGC-T		KDELR2-related disorder	Likely benign (Jul 28, 2023)
7-6463130-G-A		KDELR2-related disorder	Likely benign (Nov 08, 2023)
7-6463161-T-G		not specified	Uncertain significance (Jan 23, 2024)
7-6463163-T-C		not specified	Uncertain significance (Jan 17, 2023)
7-6466113-T-A		not specified	Uncertain significance (Jun 09, 2022)
7-6466125-C-T		not specified	Uncertain significance (Jun 16, 2024)
7-6466138-A-C		not specified	Uncertain significance (Dec 27, 2023)
7-6466167-A-C		not specified	Uncertain significance (Jun 22, 2023)
7-6466170-G-A		Osteogenesis imperfecta, type 21	Uncertain significance (Jul 23, 2021)
7-6466181-T-C		not specified	Uncertain significance (Oct 12, 2021)
7-6466190-T-C		Osteogenesis imperfecta, type 21	Pathogenic (May 24, 2021)
7-6466226-T-TG		Osteogenesis imperfecta, type 21	Pathogenic (Dec 18, 2020)
7-6466238-G-T		not specified	Uncertain significance (Nov 08, 2021)
7-6466270-T-C			Benign (May 04, 2021)
7-6466277-G-A		Osteogenesis imperfecta, type 21	Pathogenic (Dec 18, 2020)
7-6466278-G-C		not specified	Uncertain significance (Jan 24, 2024)
7-6466315-C-T		Osteogenesis imperfecta, type 21	Pathogenic (Dec 18, 2020)
7-6466319-A-G		not specified	Uncertain significance (Mar 24, 2023)
7-6469604-G-A		not specified	Uncertain significance (Nov 07, 2023)
7-6469742-C-T		not specified	Uncertain significance (Mar 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDELR2	protein_coding	protein_coding	ENST00000258739	5	38290

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.167	0.820	125742	0	5	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.804	91	115	0.789	0.00000605	1356
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Vibrio cholerae infection - Homo sapiens (human);Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;adp-ribosylation factor;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPI-dependent Golgi-to-ER retrograde traffic;Golgi-to-ER retrograde transport;COPI-mediated anterograde transport;ER to Golgi Anterograde Transport;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.124

Intolerance Scores

• loftool: 0.283
• rvis_EVS: -0.38
• rvis_percentile_EVS: 27.42

Haploinsufficiency Scores

• pHI: 0.237
• hipred: N
• hipred_score: 0.369
• ghis: 0.620

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.838

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kdelr2

Gene ontology

• 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
• Cellular component: Golgi membrane;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;cis-Golgi network;integral component of membrane;transport vesicle
• Molecular function: KDEL sequence binding