GREM2
gremlin 2, DAN family BMP antagonist, the group of DAN family
Basic information
Region (hg38): 1:240489573-240612155
Links
Phenotypes
GenCC
Source:
No genCC data.
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Tooth agenesis, selective, 9 | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Dental; Dermatologic | 26416033 |
ClinVar
This is a list of variants' phenotypes submitted to
- Tooth agenesis, selective, 9 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GREM2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 11 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 1 | 0 | 11 | 1 | 0 |
Highest pathogenic variant AF is 0.000105
Variants in GREM2
This is a list of pathogenic ClinVar variants found in the GREM2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-240492987-G-T | not specified | Uncertain significance (Apr 15, 2024) | ||
| 1-240493063-G-C | not specified | Uncertain significance (Oct 12, 2021) | ||
| 1-240493068-C-A | Tooth agenesis, selective, 9 | Pathogenic (Dec 29, 2016) | ||
| 1-240493213-C-T | not specified | Uncertain significance (Oct 25, 2022) | ||
| 1-240493226-C-T | not specified | Uncertain significance (Dec 22, 2023) | ||
| 1-240493238-G-C | Tooth agenesis, selective, 9 | Uncertain significance (May 18, 2021) | ||
| 1-240493250-G-C | Tooth agenesis, selective, 9 | Uncertain significance (Oct 13, 2023) | ||
| 1-240493251-C-T | GREM2-related disorder | Likely benign (Nov 16, 2019) | ||
| 1-240493298-G-C | not specified | Uncertain significance (May 04, 2022) | ||
| 1-240493322-C-A | not specified | Uncertain significance (May 11, 2022) | ||
| 1-240493367-C-T | not specified | Uncertain significance (Mar 14, 2023) | ||
| 1-240493438-G-A | Tooth agenesis, selective, 9 | Pathogenic (May 04, 2022) | ||
| 1-240493446-G-T | not specified | Uncertain significance (Nov 08, 2022) | ||
| 1-240493459-G-C | not specified | Uncertain significance (Dec 21, 2023) | ||
| 1-240493469-A-C | not specified | Uncertain significance (Dec 27, 2022) | ||
| 1-240509503-T-G | not specified | Benign (Apr 02, 2020) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GREM2 | protein_coding | protein_coding | ENST00000318160 | 1 | 122577 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0318 | 0.827 | 125617 | 0 | 3 | 125620 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.23 | 78 | 115 | 0.677 | 0.00000789 | 1089 |
| Missense in Polyphen | 20 | 35.743 | 0.55956 | 355 | ||
| Synonymous | 1.38 | 42 | 55.1 | 0.763 | 0.00000403 | 335 |
| Loss of Function | 1.15 | 3 | 6.07 | 0.494 | 3.11e-7 | 62 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000545 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000178 | 0.0000176 |
| Middle Eastern | 0.0000545 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Cytokine that inhibits the activity of BMP2 and BMP4 in a dose-dependent manner, and thereby modulates signaling by BMP family members. Contributes to the regulation of embryonic morphogenesis via BMP family members. Antagonizes BMP4-induced suppression of progesterone production in granulosa cells. {ECO:0000250|UniProtKB:O88273}.;
- Disease
- DISEASE: Tooth agenesis, selective, 9 (STHAG9) [MIM:617275]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG9 inheritance is autosomal dominant. {ECO:0000269|PubMed:26416033}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Signal Transduction;BMP Signalling Pathway;Signaling by BMP;Signaling by TGF-beta family members
(Consensus)
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- loftool
- 0.368
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 62.74
Haploinsufficiency Scores
- pHI
- 0.193
- hipred
- Y
- hipred_score
- 0.573
- ghis
- 0.395
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.307
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Grem2
- Phenotype
- skeleton phenotype; craniofacial phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- grem2b
- Affected structure
- pharyngeal arch 1
- Phenotype tag
- abnormal
- Phenotype quality
- malformed
Gene ontology
- Biological process
- embryonic body morphogenesis;cytokine-mediated signaling pathway;BMP signaling pathway;sequestering of BMP from receptor via BMP binding;determination of dorsal identity;regulation of cytokine activity
- Cellular component
- extracellular region;extracellular space
- Molecular function
- cytokine activity;heparin binding;BMP binding;protein homodimerization activity