CDON

cell adhesion associated, oncogene regulated, the group of Fibronectin type III domain containing|I-set domain containing

Basic information

Region (hg38): 11:125955796-126063335

Links

ENSG00000064309 ∙ NCBI:50937 ∙ OMIM:608707 ∙ HGNC:17104 ∙ Uniprot:Q4KMG0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• holoprosencephaly 11 (Moderate), mode of inheritance: AD
• holoprosencephaly 11 (Definitive), mode of inheritance: AD
• pituitary stalk interruption syndrome (Supportive), mode of inheritance: AD
• holoprosencephaly 11 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Holoprosencephaly 11	AD	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	Craniofacial; Endocrine; Neurologic; Ophthalmologic	21802063
Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus

ClinVar

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

• Pituitary stalk interruption syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDON 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			7	59	17	83
missense	1	1	183	26	11	222
nonsense			5			5
start loss						0
frameshift			15			15
inframe indel			3			3
splice donor/acceptor (+/-2bp)			6			6
splice region			5	10		15
non coding			105	37	132	274
Total	1	1	324	122	160

Variants in CDON

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

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

Position	Type	Phenotype	Significance	ClinVar
11-125956807-G-A		Holoprosencephaly sequence	Benign (Jun 14, 2016)
11-125956845-T-C		Holoprosencephaly 11	Uncertain significance (Jan 13, 2018)
11-125956862-C-T		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125956879-C-A		Holoprosencephaly 11	Uncertain significance (Jan 13, 2018)
11-125956890-G-A		Holoprosencephaly 11	Benign (Jan 12, 2018)
11-125956935-C-T		Holoprosencephaly 11	Uncertain significance (Jan 12, 2018)
11-125956942-G-A		Holoprosencephaly 11	Benign (Jan 12, 2018)
11-125956970-G-C		Holoprosencephaly 11	Likely benign (Jan 12, 2018)
11-125956971-C-T		Holoprosencephaly 11	Uncertain significance (Jan 12, 2018)
11-125957023-A-G		Holoprosencephaly 11	Likely benign (Jan 12, 2018)
11-125957026-C-T		Holoprosencephaly 11	Uncertain significance (Jan 12, 2018)
11-125957058-A-C		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957080-C-A		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957112-C-T		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957165-C-T		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957177-G-A		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957287-A-G		Holoprosencephaly 11	Uncertain significance (Feb 09, 2018)
11-125957314-G-C		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957332-G-A		Holoprosencephaly 11	Uncertain significance (Jan 13, 2018)
11-125957418-CAG-C		Holoprosencephaly sequence	Uncertain significance (Jun 14, 2016)
11-125957428-T-C		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957452-A-G		Holoprosencephaly 11	Benign (Jan 13, 2018)
11-125957461-G-A		Holoprosencephaly 11	Uncertain significance (Jan 13, 2018)
11-125957518-A-G		Holoprosencephaly 11	Benign (Jan 12, 2018)
11-125957533-A-C		Holoprosencephaly 11	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDON	protein_coding	protein_coding	ENST00000392693	19	107540

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.06e-15	0.997	125623	0	125	125748	0.000497

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.209	705	721	0.978	0.0000399	8375
Missense in Polyphen		224	253.34	0.88417		2972
Synonymous	-0.398	278	270	1.03	0.0000161	2616
Loss of Function	2.91	33	56.6	0.583	0.00000327	650

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000383	0.000383
Ashkenazi Jewish	0.000597	0.000595
East Asian	0.000327	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000768	0.000765
Middle Eastern	0.000327	0.000326
South Asian	0.000328	0.000327
Other	0.000657	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a cell-surface receptor complex that mediates cell-cell interactions between muscle precursor cells. Promotes differentiation of myogenic cells (By similarity). {ECO:0000250}.
• Disease: DISEASE: Holoprosencephaly 11 (HPE11) [MIM:614226]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. {ECO:0000269|PubMed:21802063}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hedgehog signaling pathway - Homo sapiens (human);Ectoderm Differentiation;MECP2 and Associated Rett Syndrome;Hedgehog Signaling Pathway;Developmental Biology;Signal Transduction;Hedgehog;CDO in myogenesis;Myogenesis;Ligand-receptor interactions;Hedgehog ,on, state;Signaling by Hedgehog;Signaling events mediated by the Hedgehog family (Consensus)

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.906
• rvis_EVS: 0.84
• rvis_percentile_EVS: 88.16

Haploinsufficiency Scores

• pHI: 0.125
• hipred: Y
• hipred_score: 0.681
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.426

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdon
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory 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); 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); craniofacial phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: cdon
• Affected structure: optic fissure
• Phenotype tag: abnormal
• Phenotype quality: closure incomplete

Gene ontology

• Biological process: cell fate specification;lens development in camera-type eye;cell adhesion;smoothened signaling pathway;myoblast fusion;anterior/posterior pattern specification;embryonic body morphogenesis;skeletal muscle satellite cell differentiation;cerebral cortex development;positive regulation of MAPK cascade;regulation of protein heterodimerization activity;positive regulation of myoblast differentiation;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of skeletal muscle tissue development;positive regulation of small GTPase mediated signal transduction;positive regulation of muscle cell differentiation;embryonic retina morphogenesis in camera-type eye;positive regulation of neural precursor cell proliferation
• Cellular component: plasma membrane;integral component of plasma membrane;collagen-containing extracellular matrix
• Molecular function: protein binding