CCN5

protein-coding

cellular communication network factor 5, the group of Cellular communication network factors

Gene summary

This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like (CT) domain. The encoded protein lacks the CT domain which is implicated in dimerization and heparin binding. It is 72% identical to the mouse protein at the amino acid level. This gene may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Its expression in colon tumors is reduced while the other two WISP members are overexpressed in colon tumors. It is expressed at high levels in bone tissue, and may play an important role in modulating bone turnover. [provided by RefSeq, Jul 2008]

Previous symbols:

WISP2

MANE transcript

NM_003881.4

Inheritance

—

ClinVar variants

U:67B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr20:44,714,844-44,728,509

External References & Databases

Ensembl (ENSG00000064205)

Transcript & Mutation Effects

hg38 • Region Span ~13.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCN5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003881.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	2 clinvar	5
missense			63 clinvar	1 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	67	2	2	71

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003881.4	RefSeq	NP_003872.1	4	MANE Select
ENST00000190983.5	Ensembl	ENSP00000190983.4	4	MANE Select
NM_001323369.2	RefSeq	NP_001310298.1	3	Standard
NM_001323370.2	RefSeq	NP_001310299.1	4	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372868
Coding exons: 4
Length: 13666
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125744
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.363	144	157	0.918	0.0000106	1546
Missense (PolyPhen)		47	56.977	0.82489		595
Synonymous	0.361	63	66.8	0.944	0.00000440	541
Loss of Function	0.534	8	9.80	0.816	5.04e-7	103

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00021	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000097	0.000092	rare
European (Non-Finnish)	0.00018	0.00017	rare
South Asian	0.000066	0.000065	rare
Other	0.00084	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play an important role in modulating bone turnover. Promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, inhibits osteocalcin production.;

Recessive Scores

pRec: 0.163

Intolerance Scores

RVIS EVS: 0.44
RVIS percentile EVS: 77.7

Essentials

Essential (gene trap): N