CCN6

cellular communication network factor 6, the group of Cellular communication network factors

Basic information

Region (hg38): 6:112054074-112069686

Previous symbols: [ "WISP3" ]

Links

ENSG00000112761 ∙ NCBI:8838 ∙ OMIM:603400 ∙ HGNC:12771 ∙ Uniprot:O95389 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive pseudorheumatoid arthropathy of childhood (Supportive), mode of inheritance: AR
• progressive pseudorheumatoid arthropathy of childhood (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Progressive pseudorheumatoid dysplasia	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	Musculoskeletal	6807993; 6410512; 6873109; 6431106; 8275575; 9222963; 10471507; 16152649; 19064006; 21528827

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CCN6 gene.

• not provided (128 variants)
• Progressive pseudorheumatoid dysplasia (44 variants)
• not specified (6 variants)
• Inborn genetic diseases (6 variants)
• CCN6-related condition (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCN6 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	23	5	29
missense	5	3	41	6	3	58
nonsense	9	1				10
start loss	1					1
frameshift	19	2	1			22
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			2	4	1	7
non coding		1	2	9	6	18
Total	35	8	45	38	14

Highest pathogenic variant AF is 0.0000723

Variants in CCN6

This is a list of pathogenic ClinVar variants found in the CCN6 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-112054104-A-G		Progressive pseudorheumatoid dysplasia	Benign (Nov 12, 2018)
6-112054358-A-G			Pathogenic (Dec 14, 2023)
6-112054359-T-A			Pathogenic (Jan 04, 2024)
6-112054359-T-C			Pathogenic (Jun 23, 2023)
6-112054360-G-T			Pathogenic (Feb 05, 2023)
6-112054363-G-C			Uncertain significance (Sep 01, 2023)
6-112054372-C-A			Likely benign (Aug 07, 2023)
6-112054372-C-T			Likely benign (Dec 02, 2023)
6-112054376-T-C		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
6-112054385-C-T			Likely benign (Dec 09, 2023)
6-112054386-T-C		Progressive pseudorheumatoid dysplasia	Uncertain significance (Jul 14, 2019)
6-112054390-T-C			Likely benign (Aug 17, 2023)
6-112054391-GCTGGC-G		Progressive pseudorheumatoid dysplasia	Pathogenic/Likely pathogenic (Feb 28, 2023)
6-112054398-T-C			Uncertain significance (Feb 28, 2022)
6-112054399-GGC-G		Progressive pseudorheumatoid dysplasia	Pathogenic (May 07, 2023)
6-112054400-G-A			Uncertain significance (Jun 17, 2022)
6-112054406-G-GT		Progressive pseudorheumatoid dysplasia	Pathogenic (Sep 01, 1999)
6-112054412-C-T			Likely benign (Jan 13, 2024)
6-112054413-C-T			Likely benign (Jan 09, 2023)
6-112054415-C-G			Likely benign (Apr 12, 2023)
6-112054418-C-T		Progressive pseudorheumatoid dysplasia	Conflicting classifications of pathogenicity (Dec 12, 2023)
6-112054422-G-A			Likely benign (Mar 08, 2023)
6-112054441-G-A			Benign (May 18, 2021)
6-112054634-G-A			Likely benign (Mar 01, 2024)
6-112060228-G-A			Likely benign (Aug 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCN6	protein_coding	protein_coding	ENST00000361714	5	16897

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000619	0.979	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.161	184	190	0.967	0.00000920	2435
Missense in Polyphen		65	76.724	0.8472		983
Synonymous	0.324	64	67.4	0.950	0.00000335	691
Loss of Function	2.04	8	17.1	0.467	8.21e-7	217

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000283	0.000281
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Appears to be required for normal postnatal skeletal growth and cartilage homeostasis.

Recessive Scores

• pRec: 0.152

Intolerance Scores

• rvis_EVS: 1.02
• rvis_percentile_EVS: 90.92

Haploinsufficiency Scores

• pHI: 0.0860
• hipred: N
• hipred_score: 0.294

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Ccn6
• Phenotype: endocrine/exocrine gland 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); neoplasm; normal phenotype

Zebrafish Information Network

• Gene name: ccn6
• Affected structure: pharyngeal arch cartilage
• Phenotype tag: abnormal
• Phenotype quality: fragile