CUL4A
cullin 4A, the group of Cullins|MicroRNA protein coding host genes
Basic information
Region (hg38): 13:113208192-113267108
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (15 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CUL4A 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 | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 15 | 0 | 0 |
Variants in CUL4A
This is a list of pathogenic ClinVar variants found in the CUL4A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 13-113209674-G-A | not specified | Uncertain significance (Feb 10, 2022) | ||
| 13-113209730-G-C | not specified | Uncertain significance (May 27, 2022) | ||
| 13-113209740-G-A | not specified | Uncertain significance (May 09, 2023) | ||
| 13-113209773-G-A | not specified | Uncertain significance (Jun 01, 2023) | ||
| 13-113210000-C-G | not specified | Uncertain significance (Oct 03, 2022) | ||
| 13-113210080-C-G | not specified | Uncertain significance (Jan 17, 2024) | ||
| 13-113219039-C-T | not specified | Uncertain significance (Feb 22, 2023) | ||
| 13-113229453-T-A | not specified | Uncertain significance (Aug 19, 2023) | ||
| 13-113233203-C-T | not specified | Uncertain significance (Oct 22, 2021) | ||
| 13-113233226-G-A | not specified | Uncertain significance (Jun 27, 2022) | ||
| 13-113233230-A-G | not specified | Uncertain significance (Aug 02, 2021) | ||
| 13-113233280-G-A | not specified | Uncertain significance (Feb 05, 2024) | ||
| 13-113233931-A-G | not specified | Uncertain significance (Dec 13, 2022) | ||
| 13-113235138-A-G | not specified | Likely benign (Nov 27, 2023) | ||
| 13-113242969-C-G | Uncertain significance (Jan 01, 2024) | |||
| 13-113242989-A-G | not specified | Uncertain significance (Sep 29, 2022) | ||
| 13-113245970-G-T | not specified | Uncertain significance (Jun 03, 2022) | ||
| 13-113245986-A-G | not specified | Uncertain significance (Dec 16, 2023) | ||
| 13-113246035-C-T | not specified | Uncertain significance (Jun 21, 2022) | ||
| 13-113254784-T-C | not specified | Uncertain significance (Oct 05, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CUL4A | protein_coding | protein_coding | ENST00000375440 | 20 | 56848 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000553 | 125730 | 0 | 15 | 125745 | 0.0000596 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.81 | 231 | 386 | 0.598 | 0.0000213 | 5042 |
| Missense in Polyphen | 25 | 111.4 | 0.22441 | 1442 | ||
| Synonymous | -1.01 | 169 | 153 | 1.10 | 0.00000959 | 1347 |
| Loss of Function | 5.59 | 1 | 38.3 | 0.0261 | 0.00000169 | 529 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000153 | 0.000153 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000392 | 0.000392 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. DCX(DTL) directs autoubiquitination of DTL. {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:16537899, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:24209620}.;
- Pathway
- Nucleotide excision repair - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);DNA Repair;Post-translational protein modification;Metabolism of proteins;Neddylation;Recognition of DNA damage by PCNA-containing replication complex;DNA Damage Bypass;DNA Damage Recognition in GG-NER;Formation of Incision Complex in GG-NER;Dual Incision in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Formation of TC-NER Pre-Incision Complex;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair
(Consensus)
Recessive Scores
- pRec
- 0.264
Intolerance Scores
- loftool
- 0.0395
- rvis_EVS
- -0.42
- rvis_percentile_EVS
- 25.64
Haploinsufficiency Scores
- pHI
- 0.611
- hipred
- Y
- hipred_score
- 0.739
- ghis
- 0.638
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.844
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cul4a
- Phenotype
- neoplasm; reproductive system phenotype; 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); hematopoietic system phenotype; liver/biliary system phenotype; immune system phenotype; digestive/alimentary phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- cul4a
- Affected structure
- pectoral fin
- Phenotype tag
- abnormal
- Phenotype quality
- truncated
Gene ontology
- Biological process
- G1/S transition of mitotic cell cycle;nucleotide-excision repair, DNA damage recognition;in utero embryonic development;transcription-coupled nucleotide-excision repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 5'-to lesion;ubiquitin-dependent protein catabolic process;cellular response to DNA damage stimulus;cell cycle arrest;positive regulation of cell population proliferation;negative regulation of cell population proliferation;viral process;protein ubiquitination;hemopoiesis;negative regulation of granulocyte differentiation;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;nucleotide-excision repair, DNA incision;somatic stem cell population maintenance;DNA damage response, detection of DNA damage;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;regulation of protein metabolic process;global genome nucleotide-excision repair;intrinsic apoptotic signaling pathway;positive regulation of G1/S transition of mitotic cell cycle;regulation of DNA damage checkpoint;regulation of nucleotide-excision repair
- Cellular component
- nucleoplasm;SCF ubiquitin ligase complex;cullin-RING ubiquitin ligase complex;Cul4A-RING E3 ubiquitin ligase complex;Cul4-RING E3 ubiquitin ligase complex
- Molecular function
- protein binding;ubiquitin protein ligase binding;ubiquitin protein ligase activity