CALCRL

Summary

CALCRL (calcitonin receptor like receptor, HGNC:16709) is a protein-coding gene on chromosome 2q32.1, encoding Calcitonin gene-related peptide type 1 receptor (Q16602). G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs).

Enables adrenomedullin binding activity; adrenomedullin receptor activity; and calcitonin gene-related peptide receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; cellular response to sucrose stimulus; and receptor internalization. Located in several cellular components, including endoplasmic reticulum; endosome; and lysosome. Part of CGRP receptor complex and adrenomedullin receptor complex. Implicated in hereditary lymphedema.

Source: NCBI Gene 10203 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): lymphatic malformation 8 (Limited, GenCC)
• GWAS associations: 53 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 58 total — 3 pathogenic
• Regional missense constraint (gnomAD): 3 of 7 regions constrained (≈10% of expected missense variation)
• GTEx eGene: eQTL in 18 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 7
• Drug target: yes — 10 curated mechanism-of-action drugs; 12 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 5 — Atogepant, Erenumab, Rimegepant, +2 more
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 0.70 (unconstrained)
• MANE Select transcript: NM_005795
• Notable: 58 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16709
Approved symbol	CALCRL
Name	calcitonin receptor like receptor
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Aliases	CGRPR, CRLR
Ensembl gene	ENSG00000064989
Ensembl biotype	protein_coding
OMIM	114190
Entrez	10203

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 28 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000392370

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1, TSL 4: 3, TSL 5: 2

ENST00000392370, ENST00000409998, ENST00000410068, ENST00000410102, ENST00000447403, ENST00000461244, ENST00000474212, ENST00000479784, ENST00000485973, ENST00000897822, ENST00000897823, ENST00000897824, ENST00000897825, ENST00000897826, ENST00000897827, ENST00000897828, ENST00000897829, ENST00000897830, ENST00000897831, ENST00000897832, ENST00000897833, ENST00000897834, ENST00000897835, ENST00000897836, ENST00000969621, ENST00000969622, ENST00000969623, ENST00000969624, ENST00000969625, ENST00000969626, ENST00000969627, ENST00001046174, ENST00001143272

RefSeq mRNA: 4 — MANE Select: NM_005795 NM_001271751, NM_001369434, NM_001369435, NM_005795

CCDS: CCDS2293

Canonical transcript exons

ENST00000392370 — 15 exons

Exon	Start	End
ENSE00000471484	187383173	187383305
ENSE00000471486	187380467	187380579
ENSE00000471488	187363376	187363502
ENSE00000471489	187360598	187360751
ENSE00000471493	187351920	187351961
ENSE00000783621	187352114	187352332
ENSE00000783622	187359063	187359129
ENSE00000783623	187359212	187359272
ENSE00000783626	187378940	187379031
ENSE00000783628	187380677	187380787
ENSE00001161377	187385545	187385631
ENSE00001366268	187387666	187387756
ENSE00001390679	187387329	187387493
ENSE00001585253	187448039	187448252
ENSE00003847958	187341964	187346399

Expression profiles

Bgee: expression breadth ubiquitous, 227 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.8425 / max 2014.6905, expressed in 1192 samples.

Highest expression (Bgee): lung, upper lobe of left lung, upper lobe of lung, calcaneal tendon, adrenal tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CALCRL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	1.4e-71	+0.82	2:187300439:A:G
Artery Aorta	eqtl	2.7e-29	+0.63	2:187377642:A:G
Nerve Tibial	eqtl	2.3e-12	+0.34	2:187377642:A:G
Artery Coronary	eqtl	1.1e-11	+0.57	2:187138391:T:C
Brain Cerebellar Hemisphere	eqtl	1.0e-08	+0.23	2:187346716:C:T
Adipose Subcutaneous	eqtl	9.2e-07	+0.20	2:187300439:A:G
Artery Tibial	sqtl	1.6e-05	+0.66	2:187462224:C:T
Brain Cerebellum	eqtl	1.9e-05	-0.24	2:187405610:A:G
Lung	sqtl	6.2e-05	-0.26	2:187516675:A:G
Whole Blood	eqtl	8.0e-05	+0.14	2:187445148:G:A
Adipose Subcutaneous	sqtl	1.3e-04	-0.31	2:187442607:A:T
Ovary	eqtl	3.3e-03	-0.25	2:187303332:A:G
Heart Atrial Appendage	sqtl	8.4e-03	+1.48	2:188278614:G:A
Muscle Skeletal	eqtl	1.0e-02	+0.14	2:187467463:C:A
Cells EBV-transformed lymphocytes	eqtl	1.2e-02	-0.29	2:187467463:C:A
Brain Spinal cord cervical c-1	eqtl	1.2e-02	+0.20	2:187483943:T:G
Muscle Skeletal	sqtl	1.5e-02	+0.79	2:187447978:T:C
Cells Cultured fibroblasts	eqtl	1.7e-02	+0.82	2:187254814:A:T
Esophagus Mucosa	sqtl	2.3e-02	+0.63	2:187010760:G:A
Stomach	eqtl	2.7e-02	+0.72	2:187664882:TA:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
32796	16.9534	955
32797	5.4063	1052
32795	0.4827	212

Top tissues by expression

showing 100 of 274 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	96.23	gold quality
upper lobe of left lung	UBERON:0008952	93.31	gold quality
upper lobe of lung	UBERON:0008948	93.28	gold quality
calcaneal tendon	UBERON:0003701	93.23	gold quality
lung	UBERON:0002048	92.77	gold quality
adrenal tissue	UBERON:0018303	91.80	gold quality
gall bladder	UBERON:0002110	91.71	gold quality
lower lobe of lung	UBERON:0008949	91.66	gold quality
right coronary artery	UBERON:0001625	91.63	gold quality
omental fat pad	UBERON:0010414	90.11	gold quality
peritoneum	UBERON:0002358	90.01	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.40	gold quality
left coronary artery	UBERON:0001626	89.07	gold quality
tendon	UBERON:0000043	88.24	gold quality
smooth muscle tissue	UBERON:0001135	87.85	gold quality
coronary artery	UBERON:0001621	87.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.06	gold quality
popliteal artery	UBERON:0002250	86.99	gold quality
tibial artery	UBERON:0007610	86.98	gold quality
right lobe of thyroid gland	UBERON:0001119	86.33	gold quality
visceral pleura	UBERON:0002401	85.71	gold quality
left lobe of thyroid gland	UBERON:0001120	85.57	gold quality
mucosa of stomach	UBERON:0001199	85.41	gold quality
thyroid gland	UBERON:0002046	85.36	gold quality
tendon of biceps brachii	UBERON:0008188	85.16	gold quality
adipose tissue	UBERON:0001013	84.87	gold quality
connective tissue	UBERON:0002384	84.39	gold quality
colonic epithelium	UBERON:0000397	84.31	gold quality
right atrium auricular region	UBERON:0006631	83.75	gold quality
aorta	UBERON:0000947	83.55	gold quality
rectum	UBERON:0001052	82.77	gold quality
pleura	UBERON:0000977	82.40	gold quality
apex of heart	UBERON:0002098	82.30	gold quality
heart	UBERON:0000948	82.18	gold quality
body of uterus	UBERON:0009853	82.15	gold quality
metanephros cortex	UBERON:0010533	82.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.03	gold quality
cardiac atrium	UBERON:0002081	81.94	gold quality
vermiform appendix	UBERON:0001154	81.87	gold quality
parietal pleura	UBERON:0002400	81.47	gold quality
heart left ventricle	UBERON:0002084	81.28	gold quality
germinal epithelium of ovary	UBERON:0001304	81.01	gold quality
endocervix	UBERON:0000458	80.92	gold quality
cardiac ventricle	UBERON:0002082	80.92	gold quality
left uterine tube	UBERON:0001303	80.91	gold quality
minor salivary gland	UBERON:0001830	80.87	gold quality
tibial nerve	UBERON:0001323	80.75	gold quality
islet of Langerhans	UBERON:0000006	80.41	gold quality
ectocervix	UBERON:0012249	80.33	gold quality
descending thoracic aorta	UBERON:0002345	79.91	gold quality
right ovary	UBERON:0002118	79.84	gold quality
superficial temporal artery	UBERON:0001614	79.57	gold quality
left ovary	UBERON:0002119	79.45	gold quality
endometrium	UBERON:0001295	79.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.40	gold quality
thoracic aorta	UBERON:0001515	79.38	gold quality
ascending aorta	UBERON:0001496	79.31	gold quality
ovary	UBERON:0000992	79.26	gold quality
lymph node	UBERON:0000029	78.64	gold quality
uterus	UBERON:0000995	78.56	gold quality
caecum	UBERON:0001153	78.22	gold quality
myometrium	UBERON:0001296	78.15	gold quality
stromal cell of endometrium	CL:0002255	78.07	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	78.07	gold quality
decidua	UBERON:0002450	77.68	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	77.51	gold quality
esophagus mucosa	UBERON:0002469	77.33	gold quality
mouth mucosa	UBERON:0003729	77.24	gold quality
esophagus	UBERON:0001043	77.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.99	gold quality
female reproductive system	UBERON:0000474	76.83	gold quality
adrenal gland	UBERON:0002369	76.63	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.55	gold quality
lower esophagus	UBERON:0013473	76.53	gold quality
heart right ventricle	UBERON:0002080	76.35	gold quality
spinal cord	UBERON:0002240	76.07	gold quality
muscle of leg	UBERON:0001383	76.06	gold quality
vagina	UBERON:0000996	76.04	gold quality
left adrenal gland cortex	UBERON:0035825	75.69	gold quality
gastrocnemius	UBERON:0001388	75.50	gold quality
left adrenal gland	UBERON:0001234	75.43	gold quality
saliva-secreting gland	UBERON:0001044	75.29	gold quality
urinary bladder	UBERON:0001255	75.20	gold quality
right adrenal gland cortex	UBERON:0035827	75.20	gold quality
adenohypophysis	UBERON:0002196	75.17	gold quality
skin of abdomen	UBERON:0001416	75.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	74.58	gold quality
layer of synovial tissue	UBERON:0007616	74.54	gold quality
stomach	UBERON:0000945	74.35	gold quality
pancreas	UBERON:0001264	74.26	gold quality
endothelial cell	CL:0000115	74.21	silver quality
adrenal cortex	UBERON:0001235	74.07	gold quality
diaphragm	UBERON:0001103	74.05	gold quality
adult mammalian kidney	UBERON:0000082	73.86	gold quality
muscle organ	UBERON:0001630	73.65	gold quality
skin of leg	UBERON:0001511	73.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.38	gold quality
right adrenal gland	UBERON:0001233	73.37	gold quality
zone of skin	UBERON:0000014	73.14	gold quality
monocyte	CL:0000576	72.99	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	2478.47
E-MTAB-8142	yes	872.98
E-GEOD-135922	yes	595.44
E-MTAB-10287	yes	65.40
E-HCAD-1	yes	54.06
E-HCAD-11	yes	40.83
E-GEOD-134144	yes	40.49
E-HCAD-10	yes	38.34
E-MTAB-6701	yes	32.59
E-MTAB-8410	yes	28.12
E-CURD-46	yes	27.60
E-HCAD-9	yes	16.61
E-MTAB-6678	yes	14.15
E-CURD-112	yes	7.95
E-MTAB-10553	yes	7.95

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lung	tissue	72.4	medium
Adipose tissue	tissue	66.3	medium
Putamen	tissue	27.6
Medulla oblongata	tissue	26.7
Thyroid gland	tissue	26.4	low
Cervix	tissue	26.2	high
Smooth muscle	tissue	25.3	not detected
Ovary	tissue	24.7	medium
Spinal cord	tissue	24.6
Gallbladder	tissue	22.8	medium
Basal ganglia	tissue	21.8	low
Endometrium 1	tissue	20.1	low
Heart muscle	tissue	19.1	not detected
Tongue	tissue	18.9
Ventral forebrain	tissue	18.5
Substantia nigra	tissue	15.3
Pons	tissue	14.8
Midbrain	tissue	14.2
Superior colliculi	tissue	14.2
Thalamus	tissue	13.6
Urinary bladder	tissue	13.2	medium
Kidney	tissue	13.1	medium
Parathyroid gland	tissue	12.1
Liver	tissue	11.8	low
Septum	tissue	11.6
Appendix	tissue	11.6	medium
Corpus callosum	tissue	11.4
Placenta	tissue	10.9	medium
Locus coeruleus	tissue	10.7
Fallopian tube	tissue	10.7	low
Breast	tissue	10.5	medium
Olfactory bulb	tissue	9.2
Rectum	tissue	8.9	medium
Tonsil	tissue	8.6	high
Prefrontal cortex	tissue	8.5
Cerebral cortex	tissue	8.5	medium
Hypothalamus	tissue	8.5
Esophagus	tissue	8.1	high
Spleen	tissue	8.1	low
Hippocampal formation	tissue	8.0
Hippocampus	tissue	7.7	medium
Choroid plexus	tissue	7.6
Periaqueductal gray	tissue	7.5
Lymph node	tissue	7.4	low
Seminal vesicle	tissue	7.3	medium
Retrosplenial and cingulate cortex	tissue	7.0
Prostate	tissue	6.8	medium
Stomach 1	tissue	6.7	high
Motor cortex	tissue	6.6
Amygdala	tissue	6.6
Retrosplenial cortex	tissue	6.6
Colon	tissue	6.4	medium
Entorhinal cortex	tissue	6.3
Nucleus accumbens	tissue	6.0
Small intestine	tissue	5.9	high
Adrenal gland	tissue	5.9	medium
Skeletal muscle	tissue	5.8	medium
Temporal cortex	tissue	5.7
Duodenum	tissue	5.6	high
Insular cortex	tissue	5.4

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cervical spinal cord, ventral horn (34.3), Cervical spinal cord, central gray (33.0), Dorsal funiculus (white matter) (31.7), Cervical spinal cord, dorsal horn (31.5), Anterior funiculus (white matter) (27.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PROX1

miRNA regulators (miRDB)

Targeting CALCRL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 225 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955

Functional genomics

gnomAD constraint: pLI 0.0155, LOEUF 0.701, missense Z 1.96 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000392370 splits into 7 regions with different missense tolerance; 3 are missense-constrained (≈10% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:187,346,187–187,360,663	222 / 265.6	0.84	no
2:187,360,664–187,360,710	2 / 18.7	0.11	yes (p 1.1e-04)
2:187,360,711–187,363,439	43 / 40.9	1.05	no
2:187,363,440–187,363,492	4 / 19.0	0.21	yes (p 5.8e-04)
2:187,363,493–187,380,483	43 / 46.6	0.92	no
2:187,380,484–187,380,526	2 / 17.1	0.12	yes (p 2.7e-04)
2:187,380,527–187,385,595	108 / 132.9	0.81	no

Literature-anchored findings (GeneRIF, showing 40)

• Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells (PMID:11693189)
• This study aimed to identify the cellular location of calcitonin receptor-like receptor (CRLR) which is pharmacologically identical to CGRP receptor-1, a putative molecular target of CGRP and adrenomedullin (PMID:11814625)
• The CGRP receptor components, RAMP1 and CRLR, are down-regulated during myeloid differentiation of CD34+ cells, and CGRP receptor selectively promotes the development of CFU-GM. (PMID:11937264)
• results show the presence of calcitonin receptor-like receptor and receptor activity-modifying proteins in middle meningeal, middle cerebral, pial, and superficial temporal vessels (PMID:11973435)
• expression at the human implantation site (PMID:12213903)
• receptor activity-modifying protein 1 binds to the CRLR (PMID:12574158)
• Cysteine residues in the extracellular loops of hCRLR and in the extracellular domain of hRAMP2 thus appear to play distinct roles in the cell surface expression and function of the receptor heterodimer. (PMID:12630808)
• findings show that human skin keratinocytes and fibroblasts express adrenomedullin and its receptors L1-R and CRLR (PMID:12684703)
• CRLR gene promoter (PMID:12824306)
• Transcriptional regulation of the CRLR gene in microvascular endothelial cells by hypoxia. (PMID:12824306)
• TNF-alpha induced time- and dose-dependent decreases in the expression of CRLR mRNA in cultured human coronary artery smooth muscle cells, thereby diminishing AM-evoked cAMP production (PMID:15245870)
• Results demonstrated in the atria of heart failure patients there is an up-regulation of CGRP receptor by an increase of RAMP1 in association with CRLR. (PMID:15300632)
• novel function for RAMP3 in the post-endocytic sorting of the calcitonin receptor-like receptor. (PMID:15613468)
• The N-terminal domain of calcitonin receptor-like receptor is an autonomously folded unit possessing a well-defined structure and is significantly involved in ligand binding and specificity. (PMID:15641806)
• among women, the T allele of the SNP rs696574 (C –> T, in intron 6) was significantly more frequent in essential hypertension subjects (PMID:15797661)
• Structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general. (PMID:16293613)
• the respective C-tails of hRAMP2 and -3 differentially affect hCRLR surface delivery and internalization (PMID:16410241)
• Endogenous CRLR is a key receptor for both adrenomedullin and CGRP in human endothelial cells. (PMID:16495482)
• Endogenous endothelial CRLR: subcellular localization, internalization and desensitization upon interaction with adrenomedullin and CGRP (PMID:16495482)
• adrenomedullin may prevent or reduce rheumatoid arthritis-fibroblast-like synoviocyte apoptosis, via up-regulation of its functional receptor CRLR/receptor activity-modifying protein-2 (PMID:16622024)
• Results will facilitate structural analysis of the recombinant protein will facilitate structural analysis of human RCP (receptor component protein), and allow further understanding of RCP function (PMID:17067815)
• CLR and RAMP1 traffic from endosomes to lysosomes by ubiquitin-independent mechanisms, where they are degraded at different rates (PMID:17310067)
• A mutated RAMP1 that cannot reach the cell surface, even in the presence of CRLR, indicating that the deficient targeting resulted from the altered conformation of the complex. (PMID:17503773)
• HRS mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor (PMID:17675298)
• Functional calcitonin gene-related peptide receptors are formed by the asymmetric assembly of a calcitonin receptor-like receptor homo-oligomer and a monomer of RAMP1. (PMID:17785463)
• There were some differences in mRNA expression for CL-R (higher) and RAMP3 (lower) in middle cerebral artery compared to coronary artery and pulmonary artery. (PMID:18198792)
• findings provided no significant linkage or association of adrenomedullin and CRLR-RAMP-2 genes with rheumatoid arthritis in the studied trio families (PMID:19210874)
• FACS analysis revealed the crucial CRLR regions (from TM1 to TM5) responsible for cell-surface translocation of receptor activity-modifying proteins. (PMID:19394311)
• Intrinsic cardiac adrenergic cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling. (PMID:19581316)
• The study suggests a possible role of CALCRL in the pathogenesis of acute primary angle closure glaucoma (PACG) but not chronic PACG. (PMID:19898635)
• Activation of calcitonin receptor and calcitonin receptor-like receptor by membrane-anchored ligands. (PMID:19903822)
• Data describe the role of residues 23-60 of the calcitonin receptor-like receptor in binding with interaction sites within the N-terminus of the calcitonin gene-related peptide receptor. (PMID:19913063)
• the hCRLR C-tail is crucial for adrenomedullin-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling. (PMID:20074556)
• Structure-function analysis of helix 8 of human calcitonin receptor-like receptor within the adrenomedullin 1 receptor (PMID:20946927)
• Unexplained infertility was characterised by lower number of vessels stained with CRLR in endometrium compared to fertile controls. (PMID:20954838)
• Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function. (PMID:21703310)
• The CRLR-RAMP2 interactions were confirmed for the full-length proteins on the cell surface by site-specific photo-crosslinking. (PMID:22102369)
• human CLR ECL3 is crucial for adrenomedullin (AM)-induced cAMP responses via three CLR/RAMP heterodimers, and activation of these heterodimers probably relies on AM-induced conformational changes (PMID:22142144)
• This study showed that CLR immunoreactivity was observed in satellite glial cells (SGCs) as well as in nerve fibers, but not in neurons. (PMID:22208649)
• CLR and RAMP1 co-localize in the enteric nervous system of the stomach, ileum and colon, and are in close proximity to their ligands CGRP and IMD (PMID:22484227)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	calcrlb	ENSDARG00000011571
mus_musculus	Calcrl	ENSMUSG00000059588
rattus_norvegicus	Calcrl	ENSRNOG00000054695

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177), ADGRG1 (ENSG00000205336), GCGR (ENSG00000215644)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1926944) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 19 distinct phenotype terms.

Mouse phenotype (MP)	Records
lethality throughout fetal growth and development, complete penetrance	2
abnormal skin condition	1
abnormal placenta labyrinth morphology	1
edema	1
small heart	1
disorganized myocardium	1
hydrops fetalis	1
abnormal lymph organ development	1
intestinal edema	1
lymphedema	1
vascular smooth muscle hypoplasia	1
abnormal myocardium compact layer morphology	1
thin myocardium compact layer	1
abnormal myocardium layer morphology	1
abnormal vascular smooth muscle morphology	1
decreased uterine NK cell number	1
increased fetal cardiomyocyte apoptosis	1
decreased fetal cardiomyocyte proliferation	1
abnormal uterine spiral artery remodeling	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	Q76LL8	99.5%	Diamond
Pongo abelii	Q5RAQ1	98.5%	Diamond
Canis lupus familiaris	Q9TU31	95.3%	Diamond
Sus scrofa	P50133	95.1%	Diamond
Xenopus tropicalis	Q0P4Y4	95.1%	Diamond
Bos taurus	Q1LZF7	95.1%	Diamond
Xenopus laevis	Q7ZXS8	95.1%	Diamond
Ovis aries	O62772	94.9%	Diamond
Gallus gallus	Q90812	89.8%	Diamond
Oryctolagus cuniculus	P79222	87.8%	Diamond
Oncorhynchus gorbuscha	Q8AXU4	86.6%	Diamond
Paralichthys olivaceus	Q9IB86	86.0%	Diamond
Cavia porcellus	O08893	85.6%	Diamond
Mesocricetus auratus	P43218	84.6%	Diamond
Didelphis virginiana	P25107	79.4%	Diamond
Meleagris gallopavo	Q91085	70.3%	Diamond
Carassius auratus	Q90308	65.2%	Diamond
Manduca sexta	P35464	53.6%	Diamond
Acheta domesticus	Q16983	53.6%	Diamond
Drosophila melanogaster	Q9W4Y2	39.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ZSWIM2	protein-coding	151112
FAM171B	protein-coding	165215
TFPI	protein-coding	7035
LINC01090	ncRNA	104355152
CALCRL-AS1	ncRNA	105373786

Protein

Protein identifiers

Calcitonin gene-related peptide type 1 receptor — Q16602 (reviewed: Q16602)

Alternative names: Calcitonin receptor-like receptor

All UniProt accessions (3): B8ZZJ4, E7EN01, Q16602

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor which specificity is determined by its interaction with receptor-activity-modifying proteins (RAMPs). Together with RAMP1, form the receptor complex for calcitonin-gene-related peptides CALCA/CGRP1 and CALCB/CGRP2. Together with RAMP2 or RAMP3, function as receptor complexes for adrenomedullin (ADM and ADM2). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. Activates cAMP-dependent pathway.

Subunit / interactions. Heterodimer of CALCRL and RAMP1; the receptor complex functions as CGRP receptor. Heterodimer of CALCRL and RAMP2 or CALCRL and RAMP3; the complexes function as adrenomedullin receptor.

Subcellular location. Cell membrane.

Tissue specificity. Predominantly expressed in the lung and heart.

Disease relevance. Lymphatic malformation 8 (LMPHM8) [MIM:618773] A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Adult patients with lymphedema may suffer from recurrent local infections. Impaired lymphatic drainage in the fetus can develop into hydrops fetalis, a severe condition characterized by excessive fluid accumulation in more than two fetal extra-vascular compartments and body cavities, placental enlargement and edema, pericardial or pleural effusion, or ascites. LMPHM8 is an autosomal recessive form characterized by onset in utero and fetal death due to non-immune hydrops fetalis. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G protein-coupled receptor 2 family.

RefSeq proteins (4): NP_001258680, NP_001356363, NP_001356364, NP_005786* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000832	GPCR_2_secretin-like	Family
IPR001879	GPCR_2_extracellular_dom	Domain
IPR003287	GPCR_2_calcitonin_rcpt_fam	Family
IPR003289	GPCR_2_CGRP1_rcpt	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR050332

Pfam: PF00002, PF02793

UniProt features (74 total): helix 20, strand 9, topological domain 7, transmembrane region 7, site 7, turn 5, sequence variant 4, glycosylation site 3, disulfide bond 3, mutagenesis site 3, modified residue 2, signal peptide 1, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

25 structures by resolution:

PDB	Title	Method	Resolution (Å)
6ZHO	Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity …	X-RAY DIFFRACTION	1.6
8AX7	Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic …	X-RAY DIFFRACTION	1.65
6ZIS	Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity …	X-RAY DIFFRACTION	1.73
4RWF	Crystal structure of the CLR:RAMP2 extracellular domain heterodimer with bound …	X-RAY DIFFRACTION	1.76
6V2E	Crystal structure of the human CLR:RAMP2 extracellular domain heterodimer with bound …	X-RAY DIFFRACTION	1.83
7P0F	Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic …	X-RAY DIFFRACTION	1.85
8AX6	Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic …	X-RAY DIFFRACTION	1.9
6D1U	Crystal structure of the human CLR:RAMP1 extracellular domain heterodimer in complex with …	X-RAY DIFFRACTION	2.05
3N7S	Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals …	X-RAY DIFFRACTION	2.1
6UVA	CryoEM Structure of the active Adrenomedullin 2 receptor G protein complex with …	ELECTRON MICROSCOPY	2.3
7P0I	Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic …	X-RAY DIFFRACTION	2.3
6UUS	CryoEM Structure of the active Adrenomedullin 2 receptor G protein complex with …	ELECTRON MICROSCOPY	2.4
4RWG	Crystal structure of the CLR:RAMP1 extracellular domain heterodimer with bound high …	X-RAY DIFFRACTION	2.44
3AQF	Crystal structure of the human CRLR/RAMP2 extracellular complex	X-RAY DIFFRACTION	2.6
6UMG	Crystal structure of erenumab Fab bound to the extracellular domain of CGRP receptor	X-RAY DIFFRACTION	2.7
8AX5	Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic …	X-RAY DIFFRACTION	2.75
3N7P	Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals …	X-RAY DIFFRACTION	2.8
5V6Y	Crystal structure of the human CLR:RAMP1 extracellular domain heterodimer with bound …	X-RAY DIFFRACTION	2.8
3N7R	Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals …	X-RAY DIFFRACTION	2.9
6UUN	CryoEM Structure of the active Adrenomedullin 1 receptor G protein complex with …	ELECTRON MICROSCOPY	3
7KNT	CryoEM structure of the apo-CGRP receptor in a detergent micelle	ELECTRON MICROSCOPY	3.15
9MM5	CGRP Receptor in complex with dC2_049	ELECTRON MICROSCOPY	3.26
6E3Y	Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor	ELECTRON MICROSCOPY	3.3
7KNU	CryoEM structure of the CGRP receptor with bound CGRP peptide in a detergent micelle	ELECTRON MICROSCOPY	3.49
9MNI	CGRP Receptor in complex with dC2_050	ELECTRON MICROSCOPY	4.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16602-F1	79.03	0.41

Antibody-complex structures (SAbDab)

6 antibodies co-crystallized with this protein: 6E3Y, 6UMG, 6UUN, 6UUS, 6UVA, ERENUMAB

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Family 2 (B) receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital malformations, Congenital malformations of skin

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH uncertain · IF supported

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 (7)

Position	Role
202	required for adm interaction
250	required for ramp3 interaction
286	required for adm2 interaction
288	required for ramp2 interaction
295	required for adm2 interaction
354	required for adm2 interaction
373	required for adm interaction

Post-translational modifications (2)

Type	Positions
Phosphoserine	420, 445

Disulfide bonds (3)

Type	Positions
Disulfide bond	48–74, 65–105, 88–127

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	66, 118, 123

Mutagenesis-validated functional residues (3)

Position	Phenotype
72	strongly reduced affinity for adrenomedullin.
92	strongly reduced affinity for adrenomedullin.
121	strongly reduced affinity for adrenomedullin.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-419812	Calcitonin-like ligand receptors	curated
R-HSA-418555	G alpha (s) signalling events	curated
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	curated
R-HSA-9855142	Cellular responses to mechanical stimuli	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-373080	Class B/2 (Secretin family receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-9860931	Response of endothelial cells to shear stress	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 338 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_BCELL_DN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, MODULE_64, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MUSCLE_CELL_PROLIFERATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MONOATOMIC_CATION_TRANSPORT, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, JIANG_TIP30_TARGETS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, INGRAM_SHH_TARGETS_DN

GO Biological Process (12): angiogenesis (GO:0001525), calcium ion transport (GO:0006816), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), protein transport (GO:0015031), receptor internalization (GO:0031623), cellular response to sucrose stimulus (GO:0071329), calcitonin gene-related peptide receptor signaling pathway (GO:1990408), adrenomedullin receptor signaling pathway (GO:1990410), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (7): adrenomedullin receptor activity (GO:0001605), calcitonin gene-related peptide receptor activity (GO:0001635), G protein-coupled receptor activity (GO:0004930), calcitonin receptor activity (GO:0004948), adrenomedullin binding (GO:1990409), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), adrenomedullin receptor complex (GO:1903143), CGRP receptor complex (GO:1990406), membrane (GO:0016020)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1
Response of endothelial cells to shear stress	1
Signal Transduction	1
GPCR ligand binding	1
Cellular responses to stimuli	1
Cellular responses to mechanical stimuli	1

GO top-level categories

37 GO namespaces:

Category	Terms
calcitonin family receptor activity	3
signal transduction	2
G protein-coupled receptor signaling pathway	2
calcitonin family receptor signaling pathway	2
cellular anatomical structure	2
endomembrane system	2
calcitonin family receptor complex	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
metal ion transport	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
receptor-mediated endocytosis	1
response to sucrose	1
cellular response to disaccharide stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
transmembrane signaling receptor activity	1
calcitonin binding	1
calcitonin family binding	1
signaling receptor activity	1
binding	1
intracellular anatomical structure	1
lytic vacuole	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
G protein-coupled receptor dimeric complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 27 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO term	NS	Evidence
adenylate cyclase-activating G protein-coupled receptor signaling pathway	BP	direct assay
adrenomedullin receptor signaling pathway	BP	direct assay
angiogenesis	BP	direct assay
calcitonin gene-related peptide receptor signaling pathway	BP	direct assay
calcium ion transport	BP	direct assay
cellular response to sucrose stimulus	BP	direct assay
protein transport	BP	direct assay
receptor internalization	BP	direct assay
CGRP receptor complex	CC	direct assay
adrenomedullin receptor complex	CC	direct assay
cytoplasm	CC	direct assay
endoplasmic reticulum	CC	direct assay
endosome	CC	direct assay
lysosome	CC	direct assay
plasma membrane	CC	direct assay
adrenomedullin binding	MF	physical interaction
adrenomedullin receptor activity	MF	direct assay
calcitonin gene-related peptide receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 878 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALCRL	RAMP1	O60894	988
CALCRL	RAMP2	O60895	979
CALCRL	ADM	P35318	979
CALCRL	RAMP3	O60896	963
CALCRL	CALCB	P10092	933
CALCRL	ADM2	Q7Z4H4	914
CALCRL	CRCP	O75575	905
CALCRL	IAPP	P10997	902
CALCRL	CALCA	P01258	878
CALCRL	TACR1	P25103	664
CALCRL	TAC1	P20366	556
CALCRL	EDN1	P05305	489
CALCRL	ACKR5	O15218	470
CALCRL	TRPV1	Q8NER1	437
CALCRL	SCT	P09683	428
CALCRL	MIOX	Q9UGB7	428

IntAct

Human interaction partners of CALCRL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
RAMP1	direct interaction	0.810	9
RAMP2	physical association	0.760	10
CALCA	physical association	0.710	3
RAMP3	physical association	0.470	4
ADM	direct interaction	0.440	1

BioGRID (14 interactions; top human partners by supporting records): RAMP1 (Affinity Capture-Luminescence; 10 records), CALCA (Co-purification), CRCP (Affinity Capture-Western), RAMP3 (Reconstituted Complex)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
CALCRL	“form complex”	“Adrenomedullin receptor AM1 complex”	binding
CALCRL	“form complex”	“Adrenomedullin receptor AM2 complex”	binding
CALCRL	“form complex”	“CGRP receptor complex”	binding

Protein complexes (CORUM) (12)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

12 complexes by size:

Complex	Subunits	Members
★ CALCA-CALCRL-Gs-RAMP1 complex	6	CALCRL, GNAS, GNB1, GNG2, RAMP1, CALCA
★ Adrenomedullin-CALCRL-Gs-RAMP2 complex	6	GNB1, GNG2, RAMP2, ADM, CALCRL, GNAS
★ Adrenomedullin-CALCRL-Gs-RAMP3 complex	6	CALCRL, GNAS, GNB1, GNG2, RAMP3, ADM
★ Adrenomedullin 2-CALCRL-Gs-RAMP3 complex	6	ADM2, CALCRL, GNAS, GNB1, GNG2, RAMP3
★ Adrenomedullin 2-CALCRL-RAMP1 complex	3	CALCRL, RAMP1, ADM2
★ Adrenomedullin 2-CALCRL-RAMP2 complex	3	ADM2, CALCRL, RAMP2
★ Adrenomedullin 2-CALCRL-RAMP3 complex	3	ADM2, CALCRL, RAMP3
★ CALCRL-CNIH4 complex	2	CALCRL, CNIH4
★ CALCRL-RAMP1 complex	2	CALCRL, RAMP1
★ CALCRL-RAMP2 complex	2	CALCRL, RAMP2
★ CALCRL-RAMP3 complex	2	CALCRL, RAMP3
★ CALCRL-SCTR complex	2	CALCRL, SCTR

Ligand–receptor pairs (CellPhoneDB) (3)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CALCRL;RAMP1		Signaling by Calcitonin
CALCRL;RAMP2		Signaling by Adrenomedullin
RAMP3;CALCRL;GPER1		Signaling by Adrenomedullin

Disease & clinical

Genetic variants

Variant evidence for CALCRL: 58 ClinVar records (3 pathogenic / likely pathogenic); 53 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	35
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
635896	Single allele	Pathogenic	criteria provided, single submitter	1
812514	NM_005795.6(CALCRL):c.611TAG[1] (p.Val205del)	Pathogenic	no assertion criteria provided	1
148022	GRCh38/hg38 2q31.3-32.1(chr2:180942902-187372388)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CALCRL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,142):

Position(s)	Effect	Δscore	Sites
2:187352112–187352113	donor_loss	1.0000	5
2:187352302	acceptor_gain	1.0000
2:187359273	acceptor_loss	1.0000	2
2:187360752–187360753	acceptor_loss	1.0000	5
2:187363503–187363504	acceptor_loss	1.0000	5
2:187379039	acceptor_gain	1.0000
2:187380465–187380466	donor_loss	1.0000	4
2:187380580–187380581	acceptor_loss	1.0000	5
2:187380581–187380582	acceptor_gain	1.0000	2
2:187380587–187380588	acceptor_gain	1.0000	2

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Renal Clear Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.58e-10
Glioblastoma Multiforme (validation)	favorable	6.86e-06
Skin Cutaneous Melanoma (TCGA)	unfavorable	0.000164
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000804

Disease associations

OMIM: gene MIM:114190 | disease phenotypes: MIM:618773

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
lymphatic malformation 8	Limited	Unknown

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Fetal anomalies	amber

Mondo (2): neurodevelopmental disorder (MONDO:0700092), lymphatic malformation 8 (MONDO:0032907)

HPO phenotypes

7 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001561	Polyhydramnios
HP:0001698	Pericardial effusion
HP:0001790	Nonimmune hydrops fetalis
HP:0002202	Pleural effusion
HP:0003826	Stillbirth
HP:0007430	Generalized edema

GWAS associations

showing 30 of 53 associations:

Study	Trait	p-value
GCST010699_91	Brain morphology (min-P)	9e-27
GCST010703_145	Brain morphology (MOSTest)	5e-22
GCST003818_47	Resting heart rate	6e-16
GCST010701_33	Cortical surface area (MOSTest)	3e-14
GCST010700_8	Cortical thickness (MOSTest)	5e-14
GCST90020024_315	A body shape index	5e-14
GCST004064_39	Waist-hip ratio	1e-12
GCST004576_118	Waist-to-hip ratio adjusted for body mass index	2e-12
GCST008058_218	Estimated glomerular filtration rate	2e-12
GCST010989_191	Body size at age 10	2e-12
GCST90002407_272	White blood cell count	2e-12
GCST010702_108	Subcortical volume (MOSTest)	4e-12
GCST004576_119	Waist-to-hip ratio adjusted for body mass index	7e-12
GCST004567_139	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1e-11
GCST004567_70	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1e-11
GCST011947_51	White matter hyperintensity volume	4e-11
GCST012227_1357	Hip circumference adjusted for BMI	6e-11
GCST008059_198	Estimated glomerular filtration rate	2e-10
GCST011950_1	White matter hyperintensity volume (adjusted for hypertension)	2e-10
GCST011953_17	White matter hyperintensity volume x hypertension interaction (2df)	2e-10
GCST002782_58	Waist-to-hip ratio adjusted for body mass index	3e-10
GCST010698_79	Subcortical volume (min-P)	3e-10
GCST011946_13	White matter hyperintensity volume	3e-10
GCST006979_474	Heel bone mineral density	4e-10
GCST011946_21	White matter hyperintensity volume	4e-10
GCST004576_115	Waist-to-hip ratio adjusted for body mass index	5e-10
GCST002782_56	Waist-to-hip ratio adjusted for body mass index	6e-10
GCST012230_57	Waist-to-hip ratio adjusted for BMI	6e-10
GCST90020025_1911	Waist-to-hip ratio adjusted for BMI	6e-10
GCST90011899_163	Aspartate aminotransferase levels	7e-10

EFO canonical traits (from GWAS)

15 canonical traits:

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004340	body mass index
EFO:0004343	waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009270	heel bone mineral density
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0005665	white matter hyperintensity measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference
EFO:0004736	aspartate aminotransferase measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2107838 (PROTEIN COMPLEX), CHEMBL2109232 (PROTEIN COMPLEX), CHEMBL2111191 (PROTEIN COMPLEX), CHEMBL3798 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CALCRL protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

10 curated-mechanism drugs:

Drug	Modality	Max phase
ATOGEPANT	Small molecule	4
ERENUMAB	Antibody	4
RIMEGEPANT	Small molecule	4
UBROGEPANT	Small molecule	4
ZAVEGEPANT HYDROCHLORIDE	Small molecule	4
TELCAGEPANT	Small molecule	3
BI-44370	Small molecule	2
DAVALINTIDE	Protein	2
MK3207	Small molecule	2
OLCEGEPANT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,950 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

12 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3991065	ATOGEPANT	4	265
CHEMBL2178422	RIMEGEPANT	4	438
CHEMBL2364638	UBROGEPANT	4	445
CHEMBL2397415	ZAVEGEPANT	4	314
CHEMBL3989767	CALCITONIN SALMON	4	690
CHEMBL2103758	PRAMLINTIDE	4	927
CHEMBL236593	TELCAGEPANT	3	265
CHEMBL4802169	CAGRILINTIDE	3
CHEMBL3334624	BI-44370	2	63
CHEMBL1910936	MK3207	2	170
CHEMBL207197	OLCEGEPANT	2	358
CHEMBL4635331	HTL-0022562	1	15

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs6710852	erenumab	Efficacy	Allele G is associated with increased clinical benefit to erenumab in people with Migraine with Aura or Migraine without Aura as compared to allele T.	PMID:36627267

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Calcitonin receptors

Binding affinities (BindingDB)

977 measured of 1011 human assays (1015 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4643140	KI	0.004 nM
CHEMBL2336421	KI	0.005 nM
FV-Hyp-TDVGPFAF	KI	0.006 nM
CHEMBL4649325	KI	0.007 nM
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-fluoro-5-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.01 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chloro-5-fluorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.01 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chloro-4-fluorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.01 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2R,5S)-2-[1-[acetyl(methyl)amino]-2,2,2-trifluoroethyl]-5-(3-chlorophenyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.01 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2R,5S)-2-[1-[acetyl(methyl)amino]-2,2,2-trifluoroethyl]-5-(3-chlorophenyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-6-methyl-5-(6-methyl-3-oxodiazinan-4-yl)oxypyridine-2-carboxamide	IC50	0.01 nM	US-10995084: Pyrrolidine derivative
(R)-1-(1,4’-bipiperidin-1’-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate	IC50	0.01 nM
CHEMBL4643006	IC50	0.01 nM
(R)-1-(1,4’-bipiperidin-1’-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl 4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate	IC50	0.011 nM
CHEMBL2336422	KI	0.011 nM
N-((R)-1-((S)-6-amino-1-oxo-1-(4-(pyridin-4-yl)piperazin-1-yl)hexan-2-ylamino)-3-(3,5-dibromo-4-hydroxyphenyl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide	KI	0.014 nM
Atogepant	KI	0.015 nM	US-10272077: Piperidinone carboxamide azaindane CGRP receptor antagonists
CHEMBL2336411	KI	0.015 nM
(3S)-N-[(3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,5-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1H-pyrrolo[2,3-b]pyridine-3,6’-5,7-dihydrocyclopenta[b]pyridine]-3’-carboxamide	KI	0.017 nM	US-10272077: Piperidinone carboxamide azaindane CGRP receptor antagonists
(R)-1-(1,4’-bipiperidin-1’-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate	IC50	0.017 nM
(R)-N-(1-(1,4’-bipiperidin-1’-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxamide	EC50	0.017 nM
CHEMBL2431249	KI	0.017 nM
CHEMBL2018517	IC50	0.019 nM
CHEMBL2431246	KI	0.019 nM
CHEMBL4848486	KI	0.019 nM
N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[[(2S)-1-oxo-3-piperidin-4-yl-1-(4-pyridin-4-ylpiperazin-1-yl)propan-2-yl]amino]propan-2-yl]-4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide	KI	0.02 nM	US-10300056: CGRP receptor antagonists
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-6-methyl-5-(6-methyl-3-oxodiazinan-4-yl)oxypyridine-2-carboxamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
3-chloro-N-[(2R)-1-[(2R,5S)-2-(2-cyanopropan-2-yl)-5-(3-fluorophenyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-fluoro-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(1-cyanocyclopropyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methoxy-5-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[2-[(2S,5R)-2-(3-chlorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-2-oxoethyl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(1-cyanocyclobutyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(3-cyanooxetan-3-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-fluoro-5-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3,5-dimethyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chlorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3,5-difluoro-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(5-chloro-2-fluorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3,5-difluoro-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-chloro-5-fluorophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-fluoro-5-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
N-[(2R)-1-[(2S,5R)-2-(3-bromophenyl)-5-(2-cyanopropan-2-yl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-fluoro-5-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.02 nM	US-10995084: Pyrrolidine derivative
FV-Tic-TDVGPFAF	KI	0.02 nM
(R)-1-(4-cyclohexylpiperazin-1-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate	IC50	0.02 nM
CHEMBL2022601	IC50	0.02 nM
CHEMBL4638635	KI	0.02 nM
CHEMBL2431253	KI	0.021 nM
(R)-1-(1,4’-bipiperidin-1’-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl 4-(7-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)piperidine-1-carboxylate	IC50	0.022 nM
CHEMBL2431256	KI	0.022 nM
CHEMBL2336416	KI	0.023 nM
CHEMBL2397415	KI	0.023 nM
CHEMBL4638938	KI	0.0251 nM
CHEMBL4875327	KI	0.026 nM
N-[(2R)-1-[(2R,5S)-2-(2-cyanopropan-2-yl)-5-(3-fluorophenyl)pyrrolidin-1-yl]-1-oxopropan-2-yl]-3-methyl-4-(6-methyl-3-oxodiazinan-4-yl)oxybenzamide	IC50	0.03 nM	US-10995084: Pyrrolidine derivative

ChEMBL bioactivities

1791 potent at pChembl≥5 of 1822 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	OLCEGEPANT
11.00	IC50	0.01	nM	CHEMBL4643006
11.00	Ki	0.01	nM	CHEMBL454791
11.00	IC50	0.01	nM	CHEMBL452966
11.00	IC50	0.01	nM	CHEMBL5810695
11.00	IC50	0.01	nM	CHEMBL5865405
11.00	IC50	0.01	nM	CHEMBL6015508
11.00	IC50	0.01	nM	CHEMBL5755575
11.00	IC50	0.01	nM	CHEMBL5978732
10.96	Ki	0.011	nM	CHEMBL2336422
10.96	Ki	0.011	nM	CHEMBL3893283
10.96	IC50	0.011	nM	CHEMBL508453
10.92	Ki	0.012	nM	CHEMBL2336424
10.89	Ki	0.013	nM	CHEMBL450668
10.89	Ki	0.0128	nM	CHEMBL450668
10.85	Ki	0.014	nM	CHEMBL2035984
10.85	Ki	0.014	nM	OLCEGEPANT
10.85	Ki	0.014	nM	CHEMBL4859941
10.82	Ki	0.015	nM	CHEMBL2336411
10.82	Ki	0.015	nM	CHEMBL3981883
10.82	Ki	0.015	nM	ATOGEPANT
10.82	Ki	0.015	nM	CHEMBL4848032
10.80	Ki	0.016	nM	CHEMBL2035985
10.77	EC50	0.017	nM	CHEMBL454791
10.77	Ki	0.017	nM	CHEMBL2431249
10.77	Ki	0.017	nM	CHEMBL3914484
10.77	IC50	0.017	nM	CHEMBL508215
10.77	Ki	0.017	nM	CHEMBL3990832
10.72	IC50	0.019	nM	CHEMBL2018517
10.72	Ki	0.019	nM	CHEMBL2431246
10.72	Ki	0.019	nM	CHEMBL4848486
10.70	IC50	0.02	nM	CHEMBL2022601
10.70	IC50	0.02	nM	OLCEGEPANT
10.70	Ki	0.02	nM	CHEMBL3114495
10.70	Ki	0.02	nM	CHEMBL264010
10.70	Ki	0.02	nM	CHEMBL2371890
10.70	Ki	0.01995	nM	CHEMBL4638112
10.70	Ki	0.02	nM	CHEMBL4638635
10.70	Ki	0.02	nM	CHEMBL4857649
10.70	IC50	0.02	nM	CHEMBL447297
10.70	Ki	0.02	nM	CHEMBL4638112
10.70	Ki	0.02	nM	CHEMBL5828757
10.70	IC50	0.02	nM	CHEMBL5740788
10.70	IC50	0.02	nM	CHEMBL5917191
10.70	IC50	0.02	nM	CHEMBL5742096
10.70	IC50	0.02	nM	CHEMBL5965987
10.70	IC50	0.02	nM	CHEMBL5760510
10.70	IC50	0.02	nM	CHEMBL5770083
10.70	IC50	0.02	nM	CHEMBL6061451
10.70	IC50	0.02	nM	CHEMBL5759145

PubChem BioAssay actives

1435 with measured affinity, of 1691 total; 50 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
N-[3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide	736593: Binding affinity to CGRP receptor (unknown origin)	ki	<0.0001	uM
N-[3-(7-chloro-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide	736593: Binding affinity to CGRP receptor (unknown origin)	ki	<0.0001	uM
N-[3-(7-ethyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide	736593: Binding affinity to CGRP receptor (unknown origin)	ki	<0.0001	uM
N-[(2R)-3-(4-chloro-2-oxo-3H-1,3-benzoxazol-6-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide	736593: Binding affinity to CGRP receptor (unknown origin)	ki	<0.0001	uM
N-[(2R)-3-(4-bromo-2-oxo-3H-1,3-benzoxazol-6-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide	736593: Binding affinity to CGRP receptor (unknown origin)	ki	<0.0001	uM
N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide	361794: Displacement of [I125]CGRP from human CGRP receptor in SK-N-MC cells	ki	<0.0001	uM
[(2R)-1-(4-cyclohexylpiperazin-1-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl] 4-(2-oxo-1H-quinolin-3-yl)piperidine-1-carboxylate	375825: Antagonist activity at human cloned CGRP receptor expressed in mouse E10 cells assessed as inhibition of CGRP-induced cAMP production	ic50	<0.0001	uM
[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl] 4-(7-fluoro-2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxylate	375825: Antagonist activity at human cloned CGRP receptor expressed in mouse E10 cells assessed as inhibition of CGRP-induced cAMP production	ic50	<0.0001	uM
[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl] 4-(8-fluoro-2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxylate	375825: Antagonist activity at human cloned CGRP receptor expressed in mouse E10 cells assessed as inhibition of CGRP-induced cAMP production	ic50	<0.0001	uM
[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl] 4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxylate	375825: Antagonist activity at human cloned CGRP receptor expressed in mouse E10 cells assessed as inhibition of CGRP-induced cAMP production	ic50	<0.0001	uM
[(2R)-1-(9-methyl-3,9-diazaspiro[5.5]undecan-3-yl)-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl] 4-(2-oxo-1H-quinolin-3-yl)piperidine-1-carboxylate	375825: Antagonist activity at human cloned CGRP receptor expressed in mouse E10 cells assessed as inhibition of CGRP-induced cAMP production	ic50	<0.0001	uM
[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl] 4-(2-oxo-1H-quinolin-3-yl)piperidine-1-carboxylate	375825: Antagonist activity at human cloned CGRP receptor expressed in mouse E10 cells assessed as inhibition of CGRP-induced cAMP production	ic50	<0.0001	uM
(3S)-3-[[(2S,3R)-2-[[(3S)-2-[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]-3-hydroxybutanoyl]amino]-4-[[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	257877: Displacement of [3H-propionyl-K24] from halphaCGRP expressed in human neuroblastoma SK-N-MC cells	ki	<0.0001	uM
N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[[(2S)-1-oxo-3-piperidin-4-yl-1-(4-pyridin-4-ylpiperazin-1-yl)propan-2-yl]amino]propan-2-yl]-4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide	1652728: Displacement of [3H]telcagepant from recombinant human CLR/RAMP1 expressed in Sf21 insect cell membranes measured after 60 mins by microbeta scintillation counting method	ki	<0.0001	uM
N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[[(2S)-1-oxo-3-piperidin-4-yl-1-(4-pyridin-4-ylpiperazin-1-yl)propan-2-yl]amino]propan-2-yl]-2-oxospiro[1H-pyrido[2,3-d][1,3]oxazine-4,4’-piperidine]-1’-carboxamide	1652728: Displacement of [3H]telcagepant from recombinant human CLR/RAMP1 expressed in Sf21 insect cell membranes measured after 60 mins by microbeta scintillation counting method	ki	<0.0001	uM
N-[(2R)-3-(3,5-dibromo-4-hydroxyphenyl)-1-oxo-1-[[(2S)-1-oxo-3-piperidin-4-yl-1-(4-pyridin-4-ylpiperazin-1-yl)propan-2-yl]amino]propan-2-yl]-4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide	1652728: Displacement of [3H]telcagepant from recombinant human CLR/RAMP1 expressed in Sf21 insect cell membranes measured after 60 mins by microbeta scintillation counting method	ki	<0.0001	uM
(2S)-1-[(2S)-2-[[2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(4R,7S,10S,13R,16S,22R)-22-amino-16-(2-amino-2-oxoethyl)-7-[(1R)-1-hydroxyethyl]-10-(hydroxymethyl)-13-(2-methylpropyl)-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexazacyclotricosane-4-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]-5-oxopentanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]propanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]acetyl]amino]propanoyl]pyrrolidine-2-carboxylic acid	1336313: Displacement of [125I]hCGRPa from human recombinant CGRP receptor expressed in CHO cells measured after 90 mins by scintillation counting method	ic50	<0.0001	uM
N-[(2S,5R,8R)-5-(2-cyanopropan-2-yl)-8-(4-fluoro-2-methylphenyl)-3-oxo-2,5,6,7-tetrahydro-1H-pyrrolizin-2-yl]-3-fluoro-5-methyl-4-[(3-methyl-6-oxo-1H-pyridazin-5-yl)oxy]benzamide	1657084: Inhibition of human CLR/RAMP1	ki	<0.0001	uM
N-[2-[(2S,5R)-2-(2-cyanopropan-2-yl)-5-(3-methylphenyl)pyrrolidin-1-yl]-2-oxoethyl]-3-methyl-4-[(3-methyl-6-oxo-1H-pyridazin-5-yl)methyl]benzamide	1657084: Inhibition of human CLR/RAMP1	ki	<0.0001	uM
N-[(2R)-1-[[(2S)-6-amino-1-oxo-1-(4-pyridin-4-ylpiperazin-1-yl)hexan-2-yl]amino]-3-(7-methyl-1H-indazol-5-yl)-1-oxopropan-2-yl]-4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide	1652728: Displacement of [3H]telcagepant from recombinant human CLR/RAMP1 expressed in Sf21 insect cell membranes measured after 60 mins by microbeta scintillation counting method	ki	<0.0001	uM
4-[1-[5-[(2,6-dimethyl-4-pyridinyl)-methylamino]-4-[2-(2-methoxypropan-2-yl)-4-pyridinyl]-2-pyridinyl]piperidin-4-yl]-3,5-dihydro-1H-1,4-benzodiazepin-2-one	1657093: Inhibition of human CLR/RAMP1 by cAMP assay	ic50	<0.0001	uM
N-[(2-cyclobutyl-6-methyl-4-pyridinyl)methyl]-5-[(1R)-1-[(3R)-3-methyl-2-oxo-1H-pyrrolo[2,3-b]pyridin-3-yl]ethyl]pyridine-2-carboxamide	1657084: Inhibition of human CLR/RAMP1	ki	<0.0001	uM
(7S)-4-chloro-7-[2-oxo-2-[4-(2-oxo-4,5-dihydro-1H-1,3-benzodiazepin-3-yl)piperidin-1-yl]ethyl]-1,9-bis(2,2,2-trifluoroethyl)-3,6,7,10-tetrahydroimidazo[4,5-i][2]benzazepine-2,8-dione	1776451: Displacement of [125I]CGRP from human CGRP receptor in human SK-N-MC cells measured after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
(7S)-4-chloro-1-ethyl-7-[2-oxo-2-[4-(2-oxo-4,5-dihydro-1H-1,3-benzodiazepin-3-yl)piperidin-1-yl]ethyl]-9-(2,2,2-trifluoroethyl)-3,6,7,10-tetrahydroimidazo[4,5-i][2]benzazepine-2,8-dione	1776451: Displacement of [125I]CGRP from human CGRP receptor in human SK-N-MC cells measured after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
(7S)-4-chloro-7-[2-oxo-2-[4-(2-oxo-4,5-dihydro-1H-1,3-benzodiazepin-3-yl)piperidin-1-yl]ethyl]-9-(2,2,2-trifluoroethyl)-3,6,7,10-tetrahydro-1H-imidazo[4,5-i][2]benzazepine-2,8-dione	1776451: Displacement of [125I]CGRP from human CGRP receptor in human SK-N-MC cells measured after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
(7S)-4-chloro-1-methyl-7-[2-oxo-2-[4-(2-oxo-4,5-dihydro-1H-1,3-benzodiazepin-3-yl)piperidin-1-yl]ethyl]-9-(2,2,2-trifluoroethyl)-3,6,7,10-tetrahydroimidazo[4,5-i][2]benzazepine-2,8-dione	1776451: Displacement of [125I]CGRP from human CGRP receptor in human SK-N-MC cells measured after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
(7S)-4-chloro-1-methyl-7-[2-oxo-2-[4-(2-oxo-4,5-dihydro-1H-pyrido[3,2-d][1,3]diazepin-3-yl)piperidin-1-yl]ethyl]-9-(2,2,2-trifluoroethyl)-3,6,7,10-tetrahydroimidazo[4,5-i][2]benzazepine-2,8-dione	1776451: Displacement of [125I]CGRP from human CGRP receptor in human SK-N-MC cells measured after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
(7S)-4-chloro-7-[2-oxo-2-[4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidin-1-yl]ethyl]-1,9-bis(2,2,2-trifluoroethyl)-3,6,7,10-tetrahydroimidazo[4,5-i][2]benzazepine-2,8-dione	1776451: Displacement of [125I]CGRP from human CGRP receptor in human SK-N-MC cells measured after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
(7S)-4-chloro-7-[2-oxo-2-[4-(2-oxo-4,5-dihydro-1H-1,3-benzodiazepin-3-yl)piperidin-1-yl]ethyl]-9-(2,2,2-trifluoroethyl)-3,6,7,10-tetrahydropyrazolo[3,4-i][2]benzazepin-8-one	1776451: Displacement of [125I]CGRP from human CGRP receptor in human SK-N-MC cells measured after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
2-[(8R)-8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide	665599: Displacement of [125I]CGRP from human recombinant CALCRL/RAMP1 receptor expressed in HEK293 cells after 3 hrs	ki	<0.0001	uM
2-[(6R)-6-(3,5-difluorophenyl)-3,3-dimethyl-2-oxopiperazin-1-yl]-N-[(2R)-2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide	772350: Displacement of [125I]-hCGRP from human CGRP receptor expressed in HEK293 cells	ki	<0.0001	uM
2-(2,10-dioxo-1,3,9-triazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-trien-3-yl)-N-[(2S)-2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide	412189: Displacement of [125I]hCGRP from human CGRP receptor expressed in HEK293 cells coexpressing RAMP1	ki	<0.0001	uM
(3S)-3-[[(2S,3R)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]-4-[[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	257877: Displacement of [3H-propionyl-K24] from halphaCGRP expressed in human neuroblastoma SK-N-MC cells	ki	<0.0001	uM
N-[(2S)-1-[[(2R)-6-amino-1-oxo-1-(4-pyridin-4-ylpiperazin-1-yl)hexan-2-yl]amino]-3-(3,5-dibromo-4-hydroxyphenyl)-1-oxopropan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide	254577: Antagonistic activity against calcitonin gene related peptide receptor determined by measuring the formation of cyclic AMP in SK-N-MC cells	kd	<0.0001	uM
(3S)-3-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-amino-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-2-methylpropanoyl]amino]-3-hydroxybutanoyl]amino]-4-[[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxy-2-phenylethyl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid	257877: Displacement of [3H-propionyl-K24] from halphaCGRP expressed in human neuroblastoma SK-N-MC cells	ki	<0.0001	uM
(3S)-3’-[3-[(8R)-8-(3,5-difluorophenyl)-6,8-dimethyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]prop-1-ynyl]spiro[1H-pyrrolo[2,3-b]pyridine-3,6’-5,7-dihydrocyclopenta[b]pyridine]-2-one	772350: Displacement of [125I]-hCGRP from human CGRP receptor expressed in HEK293 cells	ki	<0.0001	uM
(3S)-3’-[(E)-3-[(8R)-8-(3,5-difluorophenyl)-6,8-dimethyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]prop-1-enyl]spiro[1H-pyrrolo[2,3-b]pyridine-3,6’-5,7-dihydrocyclopenta[b]pyridine]-2-one	772350: Displacement of [125I]-hCGRP from human CGRP receptor expressed in HEK293 cells	ki	<0.0001	uM
(3S)-3’-[3-[(8R)-8-(3,5-difluorophenyl)-6,8-dimethyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]propyl]spiro[1H-pyrrolo[2,3-b]pyridine-3,6’-5,7-dihydrocyclopenta[b]pyridine]-2-one	772350: Displacement of [125I]-hCGRP from human CGRP receptor expressed in HEK293 cells	ki	<0.0001	uM
4-(8-fluoro-2-oxo-1,4-dihydroquinazolin-3-yl)-N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-piperidin-1-ylpiperidin-1-yl)propan-2-yl]piperidine-1-carboxamide	361794: Displacement of [I125]CGRP from human CGRP receptor in SK-N-MC cells	ki	<0.0001	uM
2-[(6S)-6-(2,6-difluorophenyl)-3,3-dimethyl-2-oxopiperidin-1-yl]-N-[(2S)-2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide	447514: Displacement of [125I]hCGRP from human cloned CGRP receptor expressed in HEK293 cells	ki	<0.0001	uM
3-[[(3R)-2-oxospiro[1H-pyrrolo[2,3-b]pyridine-3,7’-6,8-dihydrocyclopenta[g]quinoline]-2’-yl]methyl]-1,3,9-triazatricyclo[6.3.1.04,12]dodeca-4,6,8(12)-triene-2,10-dione	475154: Displacement of [125I]human CLR from human CGRP expressed in HEK293 cells coexpressing human RAMP1	ki	<0.0001	uM
2-[(8R)-8-(3,5-difluorophenyl)-6,8-dimethyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2’-oxospiro[1,3-dihydroindene-2,3’-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide	772350: Displacement of [125I]-hCGRP from human CGRP receptor expressed in HEK293 cells	ki	<0.0001	uM
Rimegepant	710367: Displacement of [125I]-CGRP from CGRP receptor in human SK-N-MC cells after 2 hrs by gamma scintillation counter analysis	ki	<0.0001	uM
N-[[(1R)-2,3-dihydro-1H-inden-1-yl]methyl]-2,2-dimethyl-N-[[(3S)-2-oxospiro[1H-pyrrolo[2,3-b]pyridine-3,7’-6,8-dihydrocyclopenta[g]quinoline]-3’-yl]methyl]propanamide	526712: Displacement of [125I]hCGRP from human cloned CGRP receptor expressed in HEK293 cells	ki	<0.0001	uM
Zavegepant	754795: Displacement of [125I]-CGRP from CGRP receptor in human SK-N-MC cell membranes after 2 hrs by scintillation counting analysis	ki	<0.0001	uM
N-[(6S,9R)-6-(2,3-difluorophenyl)-3-(2-methyloxolan-2-yl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl]-2-oxospiro[1H-pyrido[2,3-d][1,3]oxazine-4,4’-piperidine]-1’-carboxamide	594894: Displacement of [125I]-CGRP from human recombinant CGRP receptor	ki	<0.0001	uM
N-[(6S,9R)-6-(2,3-difluorophenyl)-3-(2-methoxypropan-2-yl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl]-4-(2-oxo-3H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide	594894: Displacement of [125I]-CGRP from human recombinant CGRP receptor	ki	<0.0001	uM
N-[(6S,9R)-6-(2,3-difluorophenyl)-3-(3-methoxypentan-3-yl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-yl]-2-oxospiro[1H-pyrido[2,3-d][1,3]oxazine-4,4’-piperidine]-1’-carboxamide	594894: Displacement of [125I]-CGRP from human recombinant CGRP receptor	ki	<0.0001	uM
2-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(3S)-2-oxospiro[1H-pyrrolo[2,3-b]pyridine-3,6’-5,7-dihydrocyclopenta[b]pyridine]-3’-yl]acetamide	665599: Displacement of [125I]CGRP from human recombinant CALCRL/RAMP1 receptor expressed in HEK293 cells after 3 hrs	ki	<0.0001	uM
(2S)-2-[(7-methyl-1H-indazol-5-yl)methyl]-4-[4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidin-1-yl]-1-(4-piperidin-1-ylpiperidin-1-yl)butane-1,4-dione	656730: Antagonist activity at human CGRP receptor expressed in human SK-N-MC cells assessed as inhibition of CGRP-stimulated cAMP production	ic50	<0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases methylation, affects cotreatment	4
bisphenol A	affects expression, decreases expression	2
trichostatin A	increases expression	2
nickel sulfate	increases expression	2
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
Am 580	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
entinostat	increases expression	1
olcegepant	affects binding, decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
telcagepant	affects binding, decreases activity	1
incobotulinumtoxinA	increases expression	1
Rosiglitazone	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	decreases expression	1
Dinitrochlorobenzene	increases expression	1
Doxorubicin	decreases expression	1
Eugenol	increases expression	1
Colforsin	decreases reaction, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1

ChEMBL screening assays

196 unique, capped per target: 131 binding, 65 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2040005	Binding	Displacement of [125I]CGRP from human recombinant CALCRL/RAMP1 receptor expressed in HEK293 cells after 3 hrs	MK-8825: a potent and selective CGRP receptor antagonist with good oral activity in rats. — *Bioorg Med Chem Lett*
CHEMBL4612975	Functional	Antagonist activity at human CGRP receptor in human SK-N-MC cells assessed as inhibition of CGRP-induced cAMP production preincubated for 30 mins followed by CGRP addition and measured after 30 mins by HTRF assay	Structure-Based Drug Discovery of N-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2’-oxo-1’,2’-dihydrospiro[piperidine-4,4’-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine. — *J Med Chem*

Cellosaurus cell lines

11 cell lines: 6 spontaneously immortalized cell line, 5 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0SA	ACTOne CALCRL	Transformed cell line	Female
CVCL_E4J2	Genomeditech HEK-293 H_CALCRL+RAMP1 Reporter	Transformed cell line	Female
CVCL_H396	CHO-K1/AM1	Spontaneously immortalized cell line	Female
CVCL_H397	CHO-K1/AM2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU85	cAMP Hunter CHO-K1 CALCRL-RAMP1 Gs	Spontaneously immortalized cell line	Female
CVCL_KU86	cAMP Hunter CHO-K1 CALCRL-RAMP3 Gs	Spontaneously immortalized cell line	Female
CVCL_KW49	PathHunter CHO-K1 CALCRL-RAMP2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KW50	PathHunter CHO-K1 CALCRL-RAMP3 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZK45	GeneBLAzer CALCRL:RAMP1-CRE-bla FreeStyle 293F	Transformed cell line	Female
CVCL_ZK46	GeneBLAzer CALCRL:RAMP2-CRE-bla FreeStyle 293F	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 210 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	Phase 2/3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	Phase 2/3	COMPLETED	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	Early Phase 1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	COMPLETED	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice
NCT03381027	Not specified	COMPLETED	BABY SMART (Study of Massage Therapy, Sleep And neurodevelopMenT)
NCT03388294	Not specified	COMPLETED	Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
NCT03410810	Not specified	UNKNOWN	Childhood Outcomes of Preterm Brain Abnormalities
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Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CALCRL across ~30M SureChEMBL compounds — explore on Sugi Predict.