CALCRL

calcitonin receptor like receptor, the group of Calcitonin receptors

Basic information

Region (hg38): 2:187341964-187448460

Links

ENSG00000064989 ∙ NCBI:10203 ∙ OMIM:114190 ∙ HGNC:16709 ∙ Uniprot:Q16602 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lymphatic malformation 8 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lymphatic malformation 8	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Cardiovascular	30115739

ClinVar

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

Variants pathogenicity by type

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

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

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

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			11	2	1	14
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	11	2	4

Variants in CALCRL

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

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

Position	Type	Phenotype	Significance	ClinVar
2-187346278-C-A			Benign (Dec 31, 2019)
2-187346314-G-A		not specified	Uncertain significance (Jun 13, 2022)
2-187346330-C-T		not specified	Uncertain significance (Dec 15, 2023)
2-187352080-T-C		Lymphatic malformation 8	Benign (Jul 14, 2021)
2-187352176-G-T		not specified	Uncertain significance (Apr 06, 2023)
2-187352302-G-A		not specified	Uncertain significance (Jul 06, 2021)
2-187359080-T-C		not specified	Uncertain significance (Dec 18, 2023)
2-187359330-A-G		Lymphatic malformation 8	Benign (Jul 14, 2021)
2-187360602-G-A			Benign (Dec 31, 2019)
2-187363386-GCTA-G		Lymphatic malformation 8	Pathogenic (Mar 04, 2021)
2-187363403-G-C		not specified	Uncertain significance (May 05, 2023)
2-187363403-G-T		not specified	Uncertain significance (Jan 05, 2022)
2-187363414-C-T		not specified	Uncertain significance (Jul 25, 2023)
2-187378983-T-C		not specified	Uncertain significance (Feb 15, 2023)
2-187379025-G-C		not specified	Uncertain significance (Mar 21, 2023)
2-187380463-A-G		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
2-187380785-C-T		not specified	Likely benign (Oct 12, 2022)
2-187383279-C-G		not specified	Uncertain significance (Oct 27, 2023)
2-187383295-G-A		not specified	Likely benign (Sep 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CALCRL	protein_coding	protein_coding	ENST00000409998	12	105332

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0147	125700	0	11	125711	0.0000438

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.09	144	234	0.615	0.0000110	3047
Missense in Polyphen		28	62.721	0.44642		870
Synonymous	0.626	76	83.3	0.913	0.00000433	812
Loss of Function	4.18	3	26.0	0.115	0.00000118	326

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000884	0.0000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for calcitonin-gene-related peptide (CGRP) together with RAMP1 and receptor for adrenomedullin together with RAMP3 (By similarity). Receptor for adrenomedullin together with RAMP2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. {ECO:0000250, ECO:0000269|PubMed:22102369}.
• Pathway: Vascular smooth muscle contraction - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Endothelin Pathways;GPCRs, Class B Secretin-like;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Calcitonin-like ligand receptors;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.401
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.76

Haploinsufficiency Scores

• pHI: 0.373
• hipred: Y
• hipred_score: 0.728
• ghis: 0.497

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.774

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Calcrl
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; digestive/alimentary phenotype; immune system phenotype; embryo phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: calcrla
• Affected structure: trunk vasculature
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: angiogenesis;calcium ion transport;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-activating G protein-coupled receptor signaling pathway;heart development;protein transport;receptor internalization;negative regulation of smooth muscle contraction;positive regulation of smooth muscle cell proliferation;negative regulation of inflammatory response;cellular response to sucrose stimulus;calcitonin gene-related peptide receptor signaling pathway;adrenomedullin receptor signaling pathway
• Cellular component: cytoplasm;lysosome;endosome;endoplasmic reticulum;plasma membrane;integral component of plasma membrane;adrenomedullin receptor complex;CGRP receptor complex
• Molecular function: adrenomedullin receptor activity;calcitonin gene-related peptide receptor activity;G protein-coupled receptor activity;calcitonin receptor activity;protein binding;protein transporter activity;adrenomedullin binding