COMMD1
copper metabolism domain containing 1, the group of CCC complex|COMM domain containing
Basic information
Region (hg38): 2:61888723-62147247
Previous symbols: [ "C2orf5" ]
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 COMMD1 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 | 0 | |||||
| missense | 10 | 11 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 10 | 1 | 0 |
Variants in COMMD1
This is a list of pathogenic ClinVar variants found in the COMMD1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 2-61905693-G-C | not specified | Uncertain significance (Jun 21, 2022) | ||
| 2-61905752-A-G | not specified | Uncertain significance (Dec 09, 2023) | ||
| 2-61905761-C-T | not specified | Uncertain significance (Nov 17, 2022) | ||
| 2-61905776-A-T | not specified | Uncertain significance (May 02, 2024) | ||
| 2-61905794-T-C | not specified | Uncertain significance (Apr 25, 2022) | ||
| 2-62000704-A-G | not specified | Uncertain significance (Dec 22, 2023) | ||
| 2-62000749-A-G | not specified | Uncertain significance (Jun 10, 2024) | ||
| 2-62000882-G-A | not specified | Uncertain significance (Feb 10, 2023) | ||
| 2-62000929-C-G | not specified | Uncertain significance (Jun 17, 2024) | ||
| 2-62000934-A-G | not specified | Uncertain significance (Sep 16, 2021) | ||
| 2-62000955-A-G | not specified | Likely benign (Jan 29, 2024) | ||
| 2-62000964-A-C | not specified | Uncertain significance (Nov 08, 2022) | ||
| 2-62135883-T-C | not specified | Uncertain significance (Jul 20, 2022) | ||
| 2-62135916-G-T | not specified | Uncertain significance (Jun 05, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| COMMD1 | protein_coding | protein_coding | ENST00000311832 | 3 | 258524 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.220 | 0.746 | 125730 | 0 | 17 | 125747 | 0.0000676 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0352 | 103 | 104 | 0.990 | 0.00000519 | 1241 |
| Missense in Polyphen | 30 | 32.973 | 0.90985 | 444 | ||
| Synonymous | -1.32 | 53 | 42.1 | 1.26 | 0.00000213 | 377 |
| Loss of Function | 1.77 | 2 | 7.10 | 0.281 | 3.02e-7 | 86 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000490 | 0.000489 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000616 | 0.0000615 |
| Middle Eastern | 0.000490 | 0.000489 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2 (PubMed:21778237). Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity (PubMed:15799966, PubMed:17183367, PubMed:20048074). Involved in the regulation of membrane expression and ubiquitination of SLC12A2 (PubMed:23515529). Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits and by promoting their ubiquitination presumably involving NEDD4L. Promotes the localization of SCNN1D to recycling endosomes (PubMed:14645214, PubMed:20237237, PubMed:21741370). Promotes CFTR cell surface expression through regulation of its ubiquitination (PubMed:21483833). Down-regulates SOD1 activity by interfering with its homodimerization (PubMed:20595380). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans- Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947). Can bind one copper ion per monomer (PubMed:17309234). May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5- bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in the regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNA binding and impaired transcriptional activation by HIF-1 (PubMed:20458141). Negatively regulates neuroblastoma G1/S phase cell cycle progression and cell proliferation by stimulating ubiquitination of NF-kappa-B subunit RELA and NF-kappa-B degradation in a FAM107A- and actin-dependent manner (PubMed:28604741). {ECO:0000269|PubMed:14645214, ECO:0000269|PubMed:14685266, ECO:0000269|PubMed:15799966, ECO:0000269|PubMed:16573520, ECO:0000269|PubMed:17183367, ECO:0000269|PubMed:17309234, ECO:0000269|PubMed:20048074, ECO:0000269|PubMed:20237237, ECO:0000269|PubMed:20458141, ECO:0000269|PubMed:20595380, ECO:0000269|PubMed:21483833, ECO:0000269|PubMed:21741370, ECO:0000269|PubMed:21778237, ECO:0000269|PubMed:23515529, ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28604741}.;
- Pathway
- Copper homeostasis;Post-translational protein modification;Metabolism of proteins;Neddylation;TNFalpha
(Consensus)
Intolerance Scores
- loftool
- 0.149
- rvis_EVS
- -0.05
- rvis_percentile_EVS
- 49.76
Haploinsufficiency Scores
- pHI
- 0.114
- hipred
- Y
- hipred_score
- 0.659
- ghis
- 0.548
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.688
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Commd1
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; embryo phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- Golgi to plasma membrane transport;protein transport;positive regulation of protein ubiquitination;negative regulation of NF-kappaB transcription factor activity;regulation of proteasomal ubiquitin-dependent protein catabolic process;post-translational protein modification;plasma membrane to endosome transport;copper ion homeostasis;negative regulation of sodium ion transmembrane transport;negative regulation of protein localization to cell surface
- Cellular component
- nucleus;nucleoplasm;cytoplasm;endosome;early endosome;cytosol;endosome membrane;Cul2-RING ubiquitin ligase complex;recycling endosome
- Molecular function
- copper ion binding;protein binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-3,4,5-trisphosphate binding;identical protein binding;protein homodimerization activity;phosphatidylinositol-3,4-bisphosphate binding;phosphatidic acid binding;phosphatidylinositol-3,5-bisphosphate binding