MMRN1
protein-codingmultimerin 1, the group of EMI domain containing|C1q domain containing
Gene summary
Multimerin is a massive, soluble protein found in platelets and in the endothelium of blood vessels. It is comprised of subunits linked by interchain disulfide bonds to form large, variably sized homomultimers. Multimerin is a factor V/Va-binding protein and may function as a carrier protein for platelet factor V. It may also have functions as an extracellular matrix or adhesive protein. Recently, patients with an unusual autosomal-dominant bleeding disorder (factor V Quebec) were found to have a deficiency of platelet multimerin. [provided by RefSeq, Jul 2008]
- MMRN
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~75.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0018393
Submitter: King Faisal Specialist Hospital and Research Center
Alhathal et al., 2020 (PMID: 32719396) reported a missense variant in a large male infertility cohort (n=285 infertile man and case–control fertile man). Gene is scored according to ClinGen classification. Moderate with total score of 8. Single-variant analysis (3 points), experimental evidence: Animal model (4 points) and testicular expression (1 points) (PMID: 21478856; PMID: 21079677).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MMRN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007351.3. 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 | 5 | 6 | |||
| missense | 179 | 9 | 2 | 190 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 180 | 10 | 7 | 197 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_031377.2 | 8 | MANE Select | |
| Ensembl | ENSP00000264790.2 | 8 | MANE Select | |
| RefSeq | NP_001358332.1 | 8 | Standard | |
| RefSeq | NP_001397664.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Platelet degranulation
- Response to elevated platelet cytosolic Ca2+
- Platelet activation, signaling and aggregation
- Hemostasis
Biological Process
- platelet degranulation
- cell adhesion
- blood coagulation
- positive regulation of cell-substrate adhesion
Molecular Function
- extracellular matrix structural constituent
- calcium ion binding
- protein binding
Cellular Component
- extracellular region
- extracellular matrix
- platelet alpha granule lumen
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394980
- Coding exons
- 8
- Length
- 75098
- Individuals with no LoFs
- 125554
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 183
- Defined
- 125738
- p
- 0.000732
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.10 | 709 | 631 | 1.12 | 0.0000312 | 8077 |
| Missense (PolyPhen) | 194 | 176.6 | 1.0985 | 2345 | ||
| Synonymous | -2.30 | 275 | 231 | 1.19 | 0.0000119 | 2337 |
| Loss of Function | 0.500 | 40 | 43.6 | 0.918 | 0.00000207 | 603 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0011 | 0.0011 | notable |
| Latino/Admixed American | 0.00040 | 0.00038 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.0021 | 0.0021 | notable |
| European (Non-Finnish) | 0.00036 | 0.00036 | rare |
| South Asian | 0.0019 | 0.0018 | notable |
| Other | 0.00085 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Carrier protein for platelet (but not plasma) factor V/Va. Plays a role in the storage and stabilization of factor V in platelets. Upon release following platelet activation, may limit platelet and plasma factor Va-dependent thrombin generation. Ligand for integrin alpha-IIb/beta-3 and integrin alpha-V/beta-3 on activated platelets, and may function as an extracellular matrix or adhesive protein. {ECO:0000269|PubMed:16363244, ECO:0000269|PubMed:19132231, ECO:0000269|PubMed:7629143}.;
- Disease
- DISEASE: Note=Deficiency in multimerin-1 due to proteolytic degradation within the platelet alpha granules is associated with an autosomal dominant bleeding disorder (factor V Quebec). {ECO:0000269|PubMed:8652809}.;
Recessive Scores
- pRec
- 0.168
Intolerance Scores
- LoFtool
- 0.709
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 73.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.832
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |