CEACAM1
CEA cell adhesion molecule 1, the group of CEA cell adhesion molecule family|V-set domain containing|CD molecules
Basic information
Region (hg38): 19:42507303-42561234
Previous symbols: [ "BGP" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEACAM1 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 | 2 | |||||
| missense | 7 | |||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 8 | 2 | 0 |
Variants in CEACAM1
This is a list of pathogenic ClinVar variants found in the CEACAM1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-42509149-G-T | not specified | Uncertain significance (Jun 28, 2022) | ||
| 19-42510904-A-G | not specified | Likely benign (Oct 17, 2023) | ||
| 19-42511599-T-C | not specified | Uncertain significance (Jul 05, 2023) | ||
| 19-42511605-G-C | not specified | Uncertain significance (Apr 15, 2024) | ||
| 19-42519102-C-A | not specified | Uncertain significance (Mar 20, 2023) | ||
| 19-42522070-G-T | not specified | Uncertain significance (Jan 29, 2024) | ||
| 19-42522107-T-C | not specified | Uncertain significance (Sep 01, 2021) | ||
| 19-42522175-C-T | not specified | Uncertain significance (Oct 30, 2023) | ||
| 19-42527132-G-A | Likely benign (Apr 05, 2018) | |||
| 19-42527306-G-T | Likely benign (Jun 08, 2018) | |||
| 19-42528331-C-T | not specified | Uncertain significance (Oct 04, 2015) | ||
| 19-42528358-G-A | not specified | Uncertain significance (Sep 16, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CEACAM1 | protein_coding | protein_coding | ENST00000161559 | 9 | 53931 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000788 | 0.996 | 125742 | 0 | 2 | 125744 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.580 | 262 | 290 | 0.904 | 0.0000154 | 3421 |
| Missense in Polyphen | 86 | 98.342 | 0.8745 | 1316 | ||
| Synonymous | 0.149 | 113 | 115 | 0.982 | 0.00000642 | 1074 |
| Loss of Function | 2.59 | 9 | 22.1 | 0.407 | 0.00000112 | 238 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000885 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Isoform 1: Cell adhesion protein that mediates homophilic cell adhesion in a calcium-independent manner (By similarity). Plays a role as coinhibitory receptor in immune response, insulin action and functions also as an activator during angiogenesis (PubMed:18424730, PubMed:23696226, PubMed:25363763). Its coinhibitory receptor function is phosphorylation- and PTPN6 -dependent, which in turn, suppress signal transduction of associated receptors by dephosphorylation of their downstream effectors. Plays a role in immune response, of T cells, natural killer (NK) and neutrophils (PubMed:18424730, PubMed:23696226). Upon TCR/CD3 complex stimulation, inhibits TCR-mediated cytotoxicity by blocking granule exocytosis by mediating homophilic binding to adjacent cells, allowing interaction with and phosphorylation by LCK and interaction with the TCR/CD3 complex which recruits PTPN6 resulting in dephosphorylation of CD247 and ZAP70 (PubMed:18424730). Also inhibits T cell proliferation and cytokine production through inhibition of JNK cascade and plays a crucial role in regulating autoimmunity and anti-tumor immunity by inhibiting T cell through its interaction with HAVCR2 (PubMed:25363763). Upon natural killer (NK) cells activation, inhibit KLRK1-mediated cytolysis of CEACAM1-bearing tumor cells by trans-homophilic interactions with CEACAM1 on the target cell and lead to cis-interaction between CEACAM1 and KLRK1, allowing PTPN6 recruitment and then VAV1 dephosphorylation (PubMed:23696226). Upon neutrophils activation negatively regulates IL1B production by recruiting PTPN6 to a SYK-TLR4- CEACAM1 complex, that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome. Downregulates neutrophil production by acting as a coinhibitory receptor for CSF3R by downregulating the CSF3R-STAT3 pathway through recruitment of PTPN6 that dephosphorylates CSF3R (By similarity). Also regulates insulin action by promoting INS clearance and regulating lipogenesis in liver through regulating insulin signaling (By similarity). Upon INS stimulation, undergoes phosphorylation by INSR leading to INS clearance by increasing receptor-mediated insulin endocytosis. This inernalization promotes interaction with FASN leading to receptor-mediated insulin degradation and to reduction of FASN activity leading to negative regulation of fatty acid synthesis. INSR-mediated phosphorylation also provokes a down-regulation of cell proliferation through SHC1 interaction resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 and phosphatidylinositol 3-kinase pathways (By similarity). Functions as activator in angiogenesis by promoting blood vessel remodeling through endothelial cell differentiation and migration and in arteriogenesis by increasing the number of collateral arteries and collateral vessel calibers after ischemia. Also regulates vascular permeability through the VEGFR2 signaling pathway resulting in control of nitric oxide production (By similarity). Downregulates cell growth in response to EGF through its interaction with SHC1 that mediates interaction with EGFR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity). Negatively regulates platelet aggregation by decreasing platelet adhesion on type I collagen through the GPVI-FcRgamma complex (By similarity). Inhibits cell migration and cell scattering through interaction with FLNA; interfers with the interaction of FLNA with RALA (PubMed:16291724). Mediates bile acid transport activity in a phosphorylation dependent manner (By similarity). Negatively regulates osteoclastogenesis (By similarity). {ECO:0000250|UniProtKB:P16573, ECO:0000250|UniProtKB:P31809, ECO:0000269|PubMed:16291724, ECO:0000269|PubMed:18424730, ECO:0000269|PubMed:23696226, ECO:0000269|PubMed:25363763}.;
- Pathway
- Vitamin D Receptor Pathway;Neutrophil degranulation;Extracellular matrix organization;Innate Immune System;Immune System;Fibronectin matrix formation;Cell surface interactions at the vascular wall;Hemostasis
(Consensus)
Intolerance Scores
- loftool
- 0.929
- rvis_EVS
- 0.22
- rvis_percentile_EVS
- 68.38
Haploinsufficiency Scores
- pHI
- 0.0888
- hipred
- Y
- hipred_score
- 0.570
- ghis
- 0.444
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.502
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ceacam2
- Phenotype
- endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- angiogenesis;regulation of cell growth;blood vessel development;negative regulation of T cell mediated cytotoxicity;negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target;negative regulation of protein kinase activity;cell adhesion;homophilic cell adhesion via plasma membrane adhesion molecules;integrin-mediated signaling pathway;regulation of endothelial cell migration;regulation of phosphatidylinositol 3-kinase signaling;bile acid and bile salt transport;cell migration;regulation of cell migration;negative regulation of granulocyte differentiation;negative regulation of interleukin-1 production;cellular response to insulin stimulus;common myeloid progenitor cell proliferation;insulin receptor internalization;granulocyte colony-stimulating factor signaling pathway;regulation of epidermal growth factor receptor signaling pathway;negative regulation of vascular permeability;neutrophil degranulation;negative regulation of cytotoxic T cell degranulation;wound healing, spreading of cells;regulation of endothelial cell differentiation;negative regulation of fatty acid biosynthetic process;negative regulation of T cell receptor signaling pathway;leukocyte migration;negative regulation of lipid biosynthetic process;regulation of blood vessel remodeling;regulation of ERK1 and ERK2 cascade;negative regulation of platelet aggregation;cell-cell adhesion via plasma-membrane adhesion molecules;insulin catabolic process;regulation of homophilic cell adhesion;regulation of sprouting angiogenesis;negative regulation of hepatocyte proliferation;positive regulation of vasculogenesis
- Cellular component
- plasma membrane;integral component of plasma membrane;cell-cell junction;adherens junction;basal plasma membrane;cell surface;membrane;integral component of membrane;apical plasma membrane;lateral plasma membrane;cell junction;transport vesicle membrane;microvillus membrane;specific granule membrane;T cell receptor complex;extracellular exosome;tertiary granule membrane
- Molecular function
- molecular_function;actin binding;protein binding;calmodulin binding;bile acid transmembrane transporter activity;kinase binding;protein phosphatase binding;filamin binding;identical protein binding;protein homodimerization activity;protein dimerization activity;protein tyrosine kinase binding