CNMD

protein-coding

chondromodulin, the group of BRICHOS domain containing

Gene summary

This gene encodes a glycosylated transmembrane protein that is cleaved to form a mature, secreted protein. The N-terminus of the precursor protein shares characteristics with other surfactant proteins and is sometimes called chondrosurfactant protein although no biological activity has yet been defined for it. The C-terminus of the precursor protein contains a 25 kDa mature protein called leukocyte cell-derived chemotaxin-1 or chondromodulin-1. The mature protein promotes chondrocyte growth and inhibits angiogenesis. This gene is expressed in the avascular zone of prehypertrophic cartilage and its expression decreases during chondrocyte hypertrophy and vascular invasion. The mature protein likely plays a role in endochondral bone development by permitting cartilaginous anlagen to be vascularized and replaced by bone. It may be involved also in the broad control of tissue vascularization during development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Previous symbols:

MYETS1
LECT1

MANE transcript

NM_007015.3

Inheritance

—

ClinVar variants

U:58B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr13:52,703,264-52,739,820

External References & Databases

Ensembl (ENSG00000136110)

Transcript & Mutation Effects

hg38 • Region Span ~36.6 kb

Loading mutation effect viewer...

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 CNMD variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 57

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007015.3. 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	3
missense			55 clinvar	2 clinvar		57
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	58	2	1	61

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007015.3	RefSeq	NP_008946.1	7	MANE Select
ENST00000377962.8	Ensembl	ENSP00000367198.3	7	MANE Select
NM_001011705.2	RefSeq	NP_001011705.1	7	Standard
ENST00000431550.1	Ensembl	ENSP00000396035.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

skeletal system development
endothelial cell morphogenesis
negative regulation of endothelial cell proliferation
proteoglycan metabolic process
negative regulation of angiogenesis

Cellular Component

extracellular region
endomembrane system
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377962
Coding exons: 7
Length: 36549
Individuals with no LoFs: 125525
Homozygous LoFs: 2
Heterozygous LoFs: 221
Defined: 125748
p: 0.000887

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.400	171	186	0.918	0.00000971	2188
Missense (PolyPhen)		61	61.146	0.99761		677
Synonymous	-0.125	65	63.7	1.02	0.00000332	617
Loss of Function	0.902	11	14.7	0.746	6.26e-7	199

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00022	0.00018	rare
Latino/Admixed American	0.00058	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00033	0.00028	rare
European (Non-Finnish)	0.0013	0.0012	notable
South Asian	0.0017	0.0017	notable
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Bifunctional growth regulator that stimulates the growth of cultured chondrocytes in the presence of basic fibroblast growth factor (FGF) but inhibits the growth of cultured vascular endothelial cells. May contribute to the rapid growth of cartilage and vascular invasion prior to the replacement of cartilage by bone during endochondral bone development. Inhibits in vitro tube formation and mobilization of endothelial cells. Plays a role as antiangiogenic factor in cardiac valves to suppress neovascularization. {ECO:0000269|PubMed:16980969}.;

Recessive Scores

pRec: 0.152

Intolerance Scores

RVIS EVS: -0.2
RVIS percentile EVS: 38.82

Essentials

Essential (gene trap): N