RECK
protein-codingreversion inducing cysteine rich protein with kazal motifs
Gene summary
The protein encoded by this gene is a cysteine-rich, extracellular protein with protease inhibitor-like domains whose expression is suppressed strongly in many tumors and cells transformed by various kinds of oncogenes. In normal cells, this membrane-anchored glycoprotein may serve as a negative regulator for matrix metalloproteinase-9, a key enzyme involved in tumor invasion and metastasis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
- ST15
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~87.5 kbGenCC 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 RECK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021111.3. 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 | 1 | 1 | 4 | ||
| missense | 111 | 7 | 118 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 116 | 8 | 1 | 125 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066934.1 | 21 | MANE Select | |
| Ensembl | ENSP00000367202.3 | 21 | MANE Select | |
| RefSeq | NP_001303274.1 | 16 | Standard | |
| RefSeq | NP_001303275.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| reck | Danio rerio | Structure: parachordal vessel Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MicroRNAs in cancer - Homo sapiens (human)
- inhibition of matrix metalloproteinases
- Post-translational modification: synthesis of GPI-anchored proteins
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- vasculature development
- blood vessel maturation
- sprouting angiogenesis
- embryo implantation
- extracellular matrix organization
Molecular Function
- endopeptidase inhibitor activity
- serine-type endopeptidase inhibitor activity
- protein binding
- metalloendopeptidase inhibitor activity
- Wnt-protein binding
Cellular Component
- extracellular region
- plasma membrane
- membrane
- anchored component of membrane
- Wnt signalosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377966
- Coding exons
- 21
- Length
- 88019
- Individuals with no LoFs
- 125686
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 62
- Defined
- 125748
- p
- 0.000247
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.54 | 425 | 524 | 0.811 | 0.0000273 | 6390 |
| Missense (PolyPhen) | 80 | 126.43 | 0.63278 | 1535 | ||
| Synonymous | 0.156 | 184 | 187 | 0.986 | 0.0000102 | 1802 |
| Loss of Function | 3.47 | 25 | 52.0 | 0.481 | 0.00000267 | 646 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.00056 | 0.00056 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negatively regulates matrix metalloproteinase-9 (MMP-9) by suppressing MMP-9 secretion and by direct inhibition of its enzymatic activity. RECK down-regulation by oncogenic signals may facilitate tumor invasion and metastasis. Appears to also regulate MMP-2 and MT1-MMP, which are involved in cancer progression.;
Recessive Scores
- pRec
- 0.200
Intolerance Scores
- LoFtool
- 0.778
- RVIS EVS
- -0.95
- RVIS percentile EVS
- 9.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0936
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |