CANT1

calcium activated nucleotidase 1

Basic information

Region (hg38): 17:78991715-79009867

Links

ENSG00000171302 ∙ NCBI:124583 ∙ OMIM:613165 ∙ HGNC:19721 ∙ Uniprot:Q8WVQ1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Desbuquois dysplasia 1 (Definitive), mode of inheritance: AR
• Desbuquois dysplasia (Supportive), mode of inheritance: AR
• Desbuquois dysplasia 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Desbuquois dysplasia 1	AR	Ophthalmologic	As the condition can include glaucoma, appropriate surveillance may allow early detection and management	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	1080993; 1959544; 7977470; 14679586; 14679587; 15211652; 19853239; 20358610; 20425819; 20358597; 21037275; 21412251; 21654728; 22539336

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CANT1 gene.

• not provided (178 variants)
• Desbuquois dysplasia 1 (112 variants)
• Inborn genetic diseases (26 variants)
• not specified (6 variants)
• Epiphyseal dysplasia, multiple, 7 (3 variants)
• Desbuquois syndrome (2 variants)
• Joint dislocation;Short stature (1 variants)
• CANT1-related condition (1 variants)
• Desbuquois dysplasia 1;Epiphyseal dysplasia, multiple, 7 (1 variants)
• Multiple epiphyseal dysplasia (1 variants)
• Abnormality of the skeletal system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CANT1 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			9	60	6	75
missense		6	78	5		89
nonsense	2	1	1			4
start loss						0
frameshift	6	1	2			9
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			3	1		4
non coding		1	46	12	18	77
Total	8	9	139	77	24

Highest pathogenic variant AF is 0.0000658

Variants in CANT1

This is a list of pathogenic ClinVar variants found in the CANT1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-78991756-A-C		Desbuquois dysplasia 1	Likely benign (Jan 12, 2018)
17-78991818-A-G		Desbuquois dysplasia 1	Benign (Jan 12, 2018)
17-78991819-G-A		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992066-G-T		Desbuquois dysplasia 1	Uncertain significance (Jan 12, 2018)
17-78992071-G-T		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992074-C-T		Desbuquois dysplasia 1	Benign (Jan 13, 2018)
17-78992110-C-T		Desbuquois dysplasia 1	Benign (Jan 13, 2018)
17-78992118-ACTTC-A		Desbuquois syndrome	Uncertain significance (Jun 14, 2016)
17-78992138-T-C		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992174-G-C		Desbuquois dysplasia 1	Likely benign (Jan 12, 2018)
17-78992191-G-A		Desbuquois dysplasia 1	Uncertain significance (Jan 17, 2018)
17-78992284-A-ACC		Desbuquois syndrome	Uncertain significance (Jun 14, 2016)
17-78992383-C-T		Desbuquois dysplasia 1	Uncertain significance (Jan 12, 2018)
17-78992397-G-A		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992401-G-A		Desbuquois dysplasia 1	Benign (Jan 12, 2018)
17-78992457-G-A		Desbuquois dysplasia 1	Benign (Jan 12, 2018)
17-78992494-A-G		Desbuquois dysplasia 1	Benign (Jan 13, 2018)
17-78992500-G-A		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992518-C-A		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992552-C-A		Desbuquois dysplasia 1	Likely benign (Jan 13, 2018)
17-78992552-C-G		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992586-T-C		Desbuquois dysplasia 1	Benign (Jan 13, 2018)
17-78992631-G-C		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992674-C-T		Desbuquois dysplasia 1	Uncertain significance (Jan 13, 2018)
17-78992703-G-A		Desbuquois dysplasia 1	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CANT1	protein_coding	protein_coding	ENST00000302345	3	18151

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000254	0.520	125671	0	77	125748	0.000306

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.488	243	265	0.916	0.0000192	2594
Missense in Polyphen		72	87.406	0.82374		909
Synonymous	0.943	115	129	0.894	0.0000113	812
Loss of Function	0.760	10	13.0	0.772	6.33e-7	132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000833	0.000824
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000151	0.000139
European (Non-Finnish)	0.000365	0.000360
Middle Eastern	0.000163	0.000163
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-dependent nucleotidase with a preference for UDP. The order of activity with different substrates is UDP > GDP > UTP > GTP. Has very low activity towards ADP and even lower activity towards ATP. Does not hydrolyze AMP and GMP (PubMed:12234496, PubMed:15248776, PubMed:15006348, PubMed:16835225). Involved in proteoglycan synthesis (PubMed:22539336). {ECO:0000269|PubMed:12234496, ECO:0000269|PubMed:15006348, ECO:0000269|PubMed:15248776, ECO:0000269|PubMed:16835225, ECO:0000269|PubMed:22539336}.
• Disease: DISEASE: Desbuquois dysplasia 1 (DBQD1) [MIM:251450]: A chondrodysplasia characterized by severe prenatal and postnatal growth retardation (less than -5 SD), joint laxity, short extremities, progressive scoliosis, round face, midface hypoplasia, prominent bulging eyes. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advance carpal and tarsal bone age. Two forms of Desbuquois dysplasia are distinguished on the basis of the presence or absence of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations. {ECO:0000269|PubMed:19853239, ECO:0000269|PubMed:20425819, ECO:0000269|PubMed:21037275, ECO:0000269|PubMed:21412251, ECO:0000269|PubMed:21654728, ECO:0000269|PubMed:22539336}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epiphyseal dysplasia, multiple, 7 (EDM7) [MIM:617719]: A form of multiple epiphyseal dysplasia, a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. EDM7 inheritance is autosomal recessive. {ECO:0000269|PubMed:28742282}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Pyrimidine Metabolism;GLUT-1 deficiency syndrome;UMP Synthase Deiciency (Orotic Aciduria);Congenital disorder of glycosylation CDG-IId;Lactose Synthesis;MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Neutrophil degranulation;UTP and CTP dephosphorylation II;Purine metabolism;Innate Immune System;Immune System;Pyrimidine metabolism;Purine nucleotides nucleosides metabolism;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.0660
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.69

Haploinsufficiency Scores

• pHI: 0.152
• hipred: N
• hipred_score: 0.301
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.108

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cant1
• 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); 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); vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: proteoglycan biosynthetic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;neutrophil degranulation
• Cellular component: extracellular region;endoplasmic reticulum membrane;plasma membrane;membrane;integral component of membrane;Golgi cisterna membrane;specific granule lumen;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: guanosine-diphosphatase activity;calcium ion binding;protein homodimerization activity;adenosine-diphosphatase activity;uridine-diphosphatase activity