MMRN2

protein-coding

multimerin 2, the group of EMI domain containing|C1q domain containing

Gene summary

This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

Previous symbols:

EMILIN3

MANE transcript

NM_024756.3

Inheritance

—

ClinVar variants

U:150B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr10:86,935,540-86,969,481

External References & Databases

Ensembl (ENSG00000173269)

Transcript & Mutation Effects

hg38 • Region Span ~33.9 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 MMRN2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 151

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024756.3. 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			1 clinvar		1 clinvar	2
missense			146 clinvar	11 clinvar		157
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	150	11	1	162

Loading ClinVar variants...

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_024756.3	RefSeq	NP_079032.2	7	MANE Select
ENST00000372027.10	Ensembl	ENSP00000361097.4	7	MANE Select
ENST00000474994.2	Ensembl	ENSP00000473405.1	4	Standard
ENST00000608090.1	Ensembl	ENSP00000476355.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

VEGFA-VEGFR2 Signaling Pathway

Biological Process

cell migration involved in sprouting angiogenesis
positive regulation of cell-substrate adhesion
negative regulation of vascular endothelial growth factor receptor signaling pathway
negative regulation of cell migration involved in sprouting angiogenesis

Molecular Function

extracellular matrix structural constituent
protein binding

Cellular Component

basement membrane
extracellular space
extracellular matrix
collagen-containing extracellular matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372027
Coding exons: 7
Length: 33942
Individuals with no LoFs: 125652
Homozygous LoFs: 0
Heterozygous LoFs: 96
Defined: 125748
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.05	489	559	0.875	0.0000365	6098
Missense (PolyPhen)		113	112.65	1.0031		1505
Synonymous	2.20	211	256	0.825	0.0000181	1965
Loss of Function	1.70	21	31.2	0.672	0.00000156	340

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00087	0.00087	rare
Ashkenazi Jewish	0.0011	0.0011	notable
East Asian	0.00012	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00035	0.00035	rare
South Asian	0.00010	0.000098	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits endothelial cells motility and acts as a negative regulator of angiogenesis; it downregulates KDR activation by binding VEGFA. {ECO:0000269|PubMed:22020326}.;

Recessive Scores

pRec: 0.0975

Intolerance Scores

LoFtool: 0.678
RVIS EVS: -0.51
RVIS percentile EVS: 21.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.170

Gene Damage Prediction

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