KDELR1

Summary

KDELR1 (KDEL endoplasmic reticulum protein retention receptor 1, HGNC:6304) is a protein-coding gene on chromosome 19q13.33, encoding ER lumen protein-retaining receptor 1 (P24390). Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum.

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, which is a seven-transmembrane protein. Unlike yeast, several human homologs of the ERD2 gene, constituting the KDEL receptor gene family, have been described. The protein encoded by this gene was the first member of the family to be identified, and it encodes a protein structurally and functionally similar to the yeast ERD2 gene product.

Source: NCBI Gene 10945 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 26 total
• Druggable target: yes
• MANE Select transcript: NM_006801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6304
Approved symbol	KDELR1
Name	KDEL endoplasmic reticulum protein retention receptor 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	ERD2.1, ERD2, HDEL
Ensembl gene	ENSG00000105438
Ensembl biotype	protein_coding
OMIM	131235
Entrez	10945

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000330720, ENST00000594643, ENST00000597017, ENST00000599084, ENST00000600980, ENST00000932964, ENST00000932965, ENST00000943172

RefSeq mRNA: 1 — MANE Select: NM_006801 NM_006801

CCDS: CCDS12718

Canonical transcript exons

ENST00000330720 — 5 exons

Exon	Start	End
ENSE00000717479	48384230	48384482
ENSE00001131365	48389553	48389711
ENSE00001131388	48391268	48391551
ENSE00001250873	48382575	48383327
ENSE00003636044	48390424	48390524

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 255.6435 / max 1673.8309, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181843	253.1318	1827
181842	2.5118	1299

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.88	gold quality
stromal cell of endometrium	CL:0002255	98.85	gold quality
left ovary	UBERON:0002119	98.47	gold quality
right ovary	UBERON:0002118	98.33	gold quality
endometrium epithelium	UBERON:0004811	98.33	gold quality
endocervix	UBERON:0000458	98.26	gold quality
saliva-secreting gland	UBERON:0001044	98.16	gold quality
pylorus	UBERON:0001166	98.08	gold quality
right lobe of thyroid gland	UBERON:0001119	98.03	gold quality
minor salivary gland	UBERON:0001830	98.03	gold quality
mucosa of transverse colon	UBERON:0004991	98.03	gold quality
tendon of biceps brachii	UBERON:0008188	98.02	gold quality
left lobe of thyroid gland	UBERON:0001120	98.01	gold quality
superficial temporal artery	UBERON:0001614	98.01	gold quality
right coronary artery	UBERON:0001625	98.00	gold quality
rectum	UBERON:0001052	97.99	gold quality
body of pancreas	UBERON:0001150	97.98	gold quality
cardia of stomach	UBERON:0001162	97.98	gold quality
body of stomach	UBERON:0001161	97.95	gold quality
adenohypophysis	UBERON:0002196	97.95	gold quality
islet of Langerhans	UBERON:0000006	97.94	gold quality
gall bladder	UBERON:0002110	97.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.94	gold quality
right adrenal gland	UBERON:0001233	97.93	gold quality
transverse colon	UBERON:0001157	97.89	gold quality
left adrenal gland	UBERON:0001234	97.89	gold quality
renal medulla	UBERON:0000362	97.88	gold quality
left uterine tube	UBERON:0001303	97.87	gold quality
left adrenal gland cortex	UBERON:0035825	97.87	gold quality
right adrenal gland cortex	UBERON:0035827	97.87	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	81.49
E-HCAD-4	yes	46.46
E-CURD-122	yes	37.67
E-HCAD-10	yes	27.06
E-ANND-3	yes	22.01
E-CURD-46	yes	19.72
E-MTAB-10042	yes	10.92
E-MTAB-10553	yes	9.74
E-HCAD-13	no	3.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting KDELR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548D-3P	99.87	70.67	4362

Literature-anchored findings (GeneRIF, showing 15)

• the KDEL receptor participates in the ER stress response not only by its retrieval ability but also by modulating MAP kinase signaling (PMID:12821650)
• Src relocated the KDEL receptor (KDEL-R) from the Golgi apparatus to the endoplasmic reticulum (PMID:12975382)
• our data provide evidence that KDELR, as a novel inducer of autophagy, participates in the degradation of misfolded neurodegenerative disease-related proteins. (PMID:21684323)
• Cystinosin, MPDU1, SWEETs and KDELR belong to a well-defined protein family with putative function of cargo receptors. (PMID:22363504)
• These findings reveal an unexpected GPCR-like mode of action of the KDEL-R and shed light on a core molecular control mechanism of intra-Golgi traffic. (PMID:22580821)
• It discuss the particular role of KDEL receptor signaling in the regulation of important pathways involved in the maintenance of the homeostasis of the transport apparatus, and in particular, of the Golgi complex. (PMID:23873287)
• KDEL receptor activates CREB1 and other transcription factors that upregulate transport-related genes (PMID:25117681)
• A Golgi-based KDELR-dependent signalling pathway controls invadopodia-dependent extracellular matrix degradation. (PMID:25682866)
• We propose a model whereby in analogy to previous findings (e.g., the RAS-RAF signalling pathway), PHB can act as a signalling scaffold protein to assist in KDELR-dependent Src activation (PMID:26064897)
• KDELR protein mediated the intracellular trafficking of Japanese encephalitis virus particles. (PMID:26861384)
• Data show that Golgi-based, KDEL receptor-dependent signalling promotes lysosome repositioning to the perinuclear area, involving a complex process intertwined to autophagy, lipid-droplet turnover and Golgi-mediated secretion. (PMID:30760704)
• The cell surface trafficking of PDIA1, PDIA3, and PDIA6 is dependent on KDELR1, which travels in a dynamic manner to the cell surface. This transport is assumed to result in PDI cell surface association, which differs from PDI inducible secretion into the extracellular space. (PMID:30958660)
• Transcriptomics of a KDELR1 knockout cell line reveals modulated cell adhesion properties. (PMID:31337861)
• KDEL receptor is a cell surface receptor that cycles between the plasma membrane and the Golgi via clathrin-mediated transport carriers. (PMID:32562023)
• Cell-type-specific differences in KDEL receptor clustering in mammalian cells. (PMID:32645101)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kdelr1	ENSMUSG00000002778
rattus_norvegicus	Kdelr1	ENSRNOG00000021082
drosophila_melanogaster	KdelR	FBGN0267330
caenorhabditis_elegans		WBGENE00001331
caenorhabditis_elegans		WBGENE00016195

Paralogs (2): KDELR3 (ENSG00000100196), KDELR2 (ENSG00000136240)

Protein

Protein identifiers

ER lumen protein-retaining receptor 1 — P24390 (reviewed: P24390)

Alternative names: KDEL endoplasmic reticulum protein retention receptor 1, Putative MAPK-activating protein PM23

All UniProt accessions (2): P24390, M0R1Y2

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum.

Subunit / interactions. Upon ligand binding the receptor oligomerizes and interacts with components of the transport machinery such as ARFGAP1 and ARF1.

Subcellular location. Golgi apparatus membrane. Cytoplasmic vesicle. COPI-coated vesicle membrane. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane.

Post-translational modifications. Phosphorylation by PKA at Ser-209 is required for endoplasmic reticulum retention function.

Domain organisation. Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein. This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles.

Similarity. Belongs to the ERD2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P24390-1	1	yes
P24390-2	2

RefSeq proteins (1): NP_006792* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000133	ER_ret_rcpt	Family

Pfam: PF00810

UniProt features (34 total): mutagenesis site 10, topological domain 8, transmembrane region 7, region of interest 3, site 3, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24390-F1	92.66	0.84

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 5 (interaction with the k-d-e-l motif on target proteins); 117 (interaction with the k-d-e-l motif on target proteins); 193 (important for recycling of cargo proteins with the sequence motif k-d-e-l from the golgi to the endoplasmic reticulum)

Post-translational modifications (1): 209

Mutagenesis-validated functional residues (10):

Position	Phenotype
12	loss of recycling together with cargo proteins containing the sequence motif k-d-e-l from the golgi to the endoplasmic r
32	decreased binding to the sequence motif k-d-e-l.
47	loss of recycling together with cargo proteins containing the sequence motif k-d-e-l from the golgi to the endoplasmic r
91–92	decreased binding to the sequence motif k-d-e-l.
127	loss of recycling together with cargo proteins containing the sequence motif k-d-e-l from the golgi to the endoplasmic r
158	loss of recycling together with cargo proteins containing the sequence motif k-d-e-l from the golgi to the endoplasmic r
193	loss of recycling together with cargo proteins containing the sequence motif k-d-e-l from the golgi to the endoplasmic r
204–207	loss of recycling together with cargo proteins containing the sequence motif k-d-e-l from the golgi to the endoplasmic r
209	inhibits coatomer/arf-gap recruitment, receptor redistribution, and intracellular retention of kdel ligands.
209	redistribution to the er is not affected upon pka inactivation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-9918476	Assembly and Release of Dengue Virus Virions

MSigDB gene sets: 213 (showing top): MORF_MTA1, RNGTGGGC_UNKNOWN, SWEET_KRAS_ONCOGENIC_SIGNATURE, TTTGTAG_MIR520D, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PROTEIN_LOCALIZATION_TO_ENDOPLASMIC_RETICULUM, GOBP_MAINTENANCE_OF_LOCATION, MORF_RAB6A, GOCC_COATED_VESICLE, GOBP_MAINTENANCE_OF_PROTEIN_LOCALIZATION_IN_ORGANELLE, GOCC_GOLGI_ASSOCIATED_VESICLE, GOBP_LEUKOCYTE_APOPTOTIC_PROCESS

GO Biological Process (6): protein retention in ER lumen (GO:0006621), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), protein transport (GO:0015031), T cell differentiation (GO:0030217), T cell apoptotic process (GO:0070231), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): KDEL sequence binding (GO:0005046), ER lumen protein retrieval receptor activity (GO:0046923), protein binding (GO:0005515)

GO Cellular Component (11): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), cis-Golgi network (GO:0005801), transport vesicle (GO:0030133), COPI-coated vesicle membrane (GO:0030663), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Golgi-to-ER retrograde transport	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
intracellular membrane-bounded organelle	4
endomembrane system	3
transport	2
Golgi apparatus	2
bounding membrane of organelle	2
maintenance of protein localization in endoplasmic reticulum	1
Golgi vesicle transport	1
intracellular protein localization	1
establishment of protein localization	1
lymphocyte differentiation	1
T cell activation	1
lymphocyte apoptotic process	1
cellular process	1
ER lumen protein retrieval receptor activity	1
signal sequence receptor activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasmic vesicle	1
COPI-coated vesicle	1
Golgi-associated vesicle membrane	1
coated vesicle membrane	1
endoplasmic reticulum-Golgi intermediate compartment	1
cellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

1118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDELR1	SDF2L1	Q9HCN8	866
KDELR1	SDF2	Q99470	848
KDELR1	RCN1	Q15293	840
KDELR1	COPB1	P53618	832
KDELR1	RCN2	Q14257	819
KDELR1	GOLPH3	Q9H4A6	799
KDELR1	RER1	O15258	692
KDELR1	SURF4	O15260	683
KDELR1	SEC63	Q9UGP8	635
KDELR1	POMT2	Q9UKY4	607
KDELR1	POMT1	Q9Y6A1	582
KDELR1	PREB	Q9HCU5	576
KDELR1	SEC13	P55735	565
KDELR1	SEC61A1	P38378	551
KDELR1	CALR	P27797	523

IntAct

84 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
KRT34	KDELR1	psi-mi:“MI:0915”(physical association)	0.560
KDELR1	DLG2	psi-mi:“MI:0915”(physical association)	0.560
KDELR1	DLG3	psi-mi:“MI:0915”(physical association)	0.560
KDELR1	TRAFD1	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
CLCC1	PLSCR1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
COPB1	KDELR1	psi-mi:“MI:0915”(physical association)	0.400
KDELR1	SEC23A	psi-mi:“MI:0915”(physical association)	0.400
KDELR1	KDELR1	psi-mi:“MI:2364”(proximity)	0.380
KDELR1	KDELR1	psi-mi:“MI:0403”(colocalization)	0.380
KDELR1	CCR9	psi-mi:“MI:0915”(physical association)	0.370
KDELR1	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
KDELR1	GPR35	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
KDELR1	PSMD11	psi-mi:“MI:0914”(association)	0.350
RAC1		psi-mi:“MI:0914”(association)	0.350
PRKAR1A	ADAM10	psi-mi:“MI:0914”(association)	0.350
PEBP1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (128): KDELR1 (Affinity Capture-MS), UBE3A (Affinity Capture-MS), UBL7 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), VPS36 (Affinity Capture-MS), TAX1BP1 (Affinity Capture-MS), TRAFD1 (Affinity Capture-MS), UCHL5 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), UBQLN4 (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS), PSMD6 (Affinity Capture-MS), UBQLN1 (Affinity Capture-MS), RNF115 (Affinity Capture-MS)

ESM2 similar proteins: A0A097ZPD8, A0A0E3D8M2, A0A0E3D8Q2, A0A0F7TZE0, A0A0U5GIU9, A0A140JWT2, A0A1B7YCX1, A0A1E1FFM9, A0A1Y0BRF5, A0A2I1BT01, A0A2I6PJ07, A0A2P1DP74, A0A3G9H8P0, A0A3T0ZHJ5, A0A455RAK9, A0A8D5M7T9, A9JPE3, B6HV37, E3UBL6, E9F5E8, J7FIJ6, K2RU64, M1VJS5, P0DY23, P24390, P33946, P35402, P48583, P9WEQ3, P9WEX1, P9WEX7, P9WEY0, Q0VCC1, Q15FB1, Q4WBI3, Q4WLD2, Q569A6, Q5M880, Q5U305, Q5XHA2

Diamond homologs: O42580, O43731, O44017, O76767, O94270, P18413, P18414, P24390, P33946, P33947, P33948, P35402, P48583, Q09473, Q2KJ37, Q569A6, Q5U305, Q5XHA2, Q5ZKX9, Q611C8, Q66JF2, Q68ES4, Q6P257, Q6PAB8, Q6PEH1, Q6PFS5, Q76NM1, Q7ZXS5, Q86JE5, Q8R1L4, Q8VWI1, Q99JH8, Q9CQM2, Q9ZTN2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	KDELR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	8	11.0×	3e-04
adenylate cyclase-activating G protein-coupled receptor signaling pathway	7	9.3×	3e-03
G protein-coupled receptor signaling pathway	14	6.0×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

26 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

711 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48383323:TAGGA:T	acceptor_gain	1.0000
19:48383325:GGA:G	acceptor_gain	1.0000
19:48383326:GA:G	acceptor_gain	1.0000
19:48383326:GAC:G	acceptor_loss	1.0000
19:48383328:C:CC	acceptor_gain	1.0000
19:48383329:T:C	acceptor_loss	1.0000
19:48383330:G:C	acceptor_gain	1.0000
19:48384225:GCTAC:G	donor_loss	1.0000
19:48384226:CTACC:C	donor_loss	1.0000
19:48384227:TAC:T	donor_loss	1.0000
19:48384228:A:AT	donor_loss	1.0000
19:48384229:CCTTT:C	donor_loss	1.0000
19:48389548:CCTA:C	donor_loss	1.0000
19:48389549:CTAC:C	donor_loss	1.0000
19:48389550:TA:T	donor_loss	1.0000
19:48389551:A:AT	donor_loss	1.0000
19:48389708:CCAC:C	acceptor_gain	1.0000
19:48389709:CACC:C	acceptor_gain	1.0000
19:48389710:ACC:A	acceptor_loss	1.0000
19:48389711:CCT:C	acceptor_loss	1.0000
19:48389712:CTGA:C	acceptor_loss	1.0000
19:48389713:T:G	acceptor_loss	1.0000
19:48390421:TACCT:T	donor_loss	1.0000
19:48390422:ACC:A	donor_loss	1.0000
19:48390423:CC:C	donor_loss	1.0000
19:48390525:C:A	acceptor_loss	1.0000
19:48390525:C:CC	acceptor_gain	1.0000
19:48390533:C:CT	acceptor_gain	1.0000
19:48390534:A:T	acceptor_gain	1.0000
19:48391286:T:TA	donor_gain	1.0000

AlphaMissense

1376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48384284:C:G	G184R	1.000
19:48384368:C:G	G156R	1.000
19:48384436:G:C	P133R	1.000
19:48384436:G:T	P133Q	1.000
19:48391336:C:T	G8E	1.000
19:48384252:G:C	F194L	0.999
19:48384252:G:T	F194L	0.999
19:48384254:A:G	F194L	0.999
19:48384283:C:T	G184D	0.999
19:48384286:G:T	A183E	0.999
19:48384328:C:G	R169P	0.999
19:48384329:G:T	R169S	0.999
19:48384338:A:G	W166R	0.999
19:48384338:A:T	W166R	0.999
19:48384339:G:C	N165K	0.999
19:48384339:G:T	N165K	0.999
19:48384358:C:G	R159P	0.999
19:48384359:G:T	R159S	0.999
19:48384367:C:T	G156D	0.999
19:48384370:A:G	L155P	0.999
19:48384379:A:G	L152S	0.999
19:48384430:A:G	L135P	0.999
19:48384437:G:A	P133S	0.999
19:48384437:G:T	P133T	0.999
19:48384442:A:T	I131N	0.999
19:48384445:G:T	A130D	0.999
19:48384446:C:G	A130P	0.999
19:48384453:C:A	E127D	0.999
19:48384453:C:G	E127D	0.999
19:48384454:T:A	E127V	0.999

dbSNP variants (sampled 300 via entrez): RS1000125913 (19:48392020 G>A), RS1000319960 (19:48397051 C>T), RS1000409250 (19:48392748 C>A,G,T), RS1000743486 (19:48390748 A>C), RS1000817332 (19:48386117 T>C), RS1000984746 (19:48397615 T>C), RS1001059588 (19:48396158 T>A,C), RS1001122510 (19:48383445 T>A,C,G), RS1001215324 (19:48384627 C>T), RS1001594456 (19:48395912 TG>T), RS1001627022 (19:48396129 A>G), RS1001698775 (19:48391868 G>C), RS1001778538 (19:48396802 G>A), RS1001800324 (19:48391755 CTG>C), RS1001964026 (19:48395288 C>G,T)

Disease associations

OMIM: gene MIM:131235 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066272 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.60	Kd	0.253	nM	CHEMBL5653589
9.60	ED50	0.253	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148618: Binding affinity to human KDELR1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0003	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects cotreatment, affects expression, increases abundance	1
deoxynivalenol	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
U 0126	affects expression, affects reaction	1
bisphenol B	increases expression	1
abrine	decreases expression	1
Bortezomib	decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects methylation	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Ivermectin	decreases expression	1
Methotrexate	affects response to substance	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Phthalic Acids	decreases methylation	1
Smoke	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651660	Binding	Binding affinity to human KDELR1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2ZK	Abcam HEK293T KDELR1 KO	Transformed cell line	Female
CVCL_SU14	HAP1 KDELR1 (-) 1	Cancer cell line	Male
CVCL_XP95	HAP1 KDELR1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.