CCN4

protein-coding

cellular communication network factor 4, 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 domain. This gene may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. It is expressed at a high level in fibroblast cells, and overexpressed in colon tumors. The encoded protein binds to decorin and biglycan, two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue, and possibly prevents the inhibitory activity of decorin and biglycan in tumor cell proliferation. It also attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase. It is 83% identical to the mouse protein at the amino acid level. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2011]

Previous symbols:

WISP1-OT1
WISP1-UT1
WISP1

MANE transcript

NM_003882.4

Inheritance

—

ClinVar variants

U:82B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr8:133,191,039-133,231,690

External References & Databases

Ensembl (ENSG00000104415)

Transcript & Mutation Effects

hg38 • Region Span ~40.7 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 CCN4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003882.4. 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			1 clinvar	5 clinvar	3 clinvar	9
missense			81 clinvar	3 clinvar		84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	82	8	3	93

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003882.4	RefSeq	NP_003873.1	5	MANE Select
ENST00000250160.11	Ensembl	ENSP00000250160.5	5	MANE Select
NM_001204869.2	RefSeq	NP_001191798.1	3	Standard
NM_001204870.2	RefSeq	NP_001191799.1	2	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000250160
Coding exons: 5
Length: 39306
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.216	236	246	0.961	0.0000159	2397
Missense (PolyPhen)		81	100.31	0.8075		1023
Synonymous	-1.11	111	97.0	1.14	0.00000667	723
Loss of Function	1.18	12	17.3	0.695	0.00000102	165

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Downstream regulator in the Wnt/Frizzled-signaling pathway. Associated with cell survival. Attenuates p53-mediated apoptosis in response to DNA damage through activation of AKT kinase. Up-regulates the anti-apoptotic Bcl-X(L) protein. Adheres to skin and melanoma fibroblasts. In vitro binding to skin fibroblasts occurs through the proteoglycans, decorin and biglycan. {ECO:0000269|PubMed:10716946, ECO:0000269|PubMed:11782444}.;

Recessive Scores

pRec: 0.164

Intolerance Scores

RVIS EVS: 0.78
RVIS percentile EVS: 87.18

Essentials

Essential (gene trap): N