ZC3H12A
zinc finger CCCH-type containing 12A, the group of MicroRNA protein coding host genes|Zinc fingers CCCH-type
Basic information
Region (hg38): 1:37474579-37484377
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (18 variants)
- not provided (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZC3H12A 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 | 17 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 17 | 1 | 3 |
Variants in ZC3H12A
This is a list of pathogenic ClinVar variants found in the ZC3H12A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-37475578-C-T | not specified | Likely benign (Sep 20, 2023) | ||
| 1-37475717-T-C | not specified | Uncertain significance (Dec 07, 2021) | ||
| 1-37475761-G-A | not specified | Uncertain significance (Jun 06, 2023) | ||
| 1-37475795-C-T | Benign (Jun 21, 2018) | |||
| 1-37475863-C-T | not specified | Uncertain significance (May 10, 2023) | ||
| 1-37475896-G-A | not specified | Uncertain significance (Nov 10, 2022) | ||
| 1-37480319-G-T | not specified | Uncertain significance (Oct 13, 2021) | ||
| 1-37480417-G-A | not specified | Uncertain significance (Jun 22, 2021) | ||
| 1-37480418-T-G | not specified | Uncertain significance (Jun 05, 2023) | ||
| 1-37481615-C-T | not specified | Likely benign (Aug 02, 2021) | ||
| 1-37481718-A-G | not specified | Uncertain significance (Oct 04, 2022) | ||
| 1-37481735-G-A | Benign (Apr 20, 2018) | |||
| 1-37481756-C-T | not specified | Uncertain significance (Nov 02, 2023) | ||
| 1-37481805-G-A | not specified | Uncertain significance (Jul 08, 2022) | ||
| 1-37482468-G-A | not specified | Uncertain significance (May 26, 2023) | ||
| 1-37482838-C-T | not specified | Uncertain significance (Aug 15, 2023) | ||
| 1-37482844-C-G | not specified | Uncertain significance (Jul 09, 2021) | ||
| 1-37482844-C-T | not specified | Uncertain significance (Aug 14, 2023) | ||
| 1-37482878-G-A | not specified | Likely benign (Jan 19, 2024) | ||
| 1-37482964-G-T | not specified | Uncertain significance (Jan 23, 2024) | ||
| 1-37483102-G-A | not specified | Likely benign (Feb 12, 2024) | ||
| 1-37483335-C-T | Benign (Jun 21, 2018) | |||
| 1-37483406-C-T | not specified | Uncertain significance (Sep 14, 2022) | ||
| 1-37483510-C-T | not specified | Uncertain significance (Jun 12, 2023) | ||
| 1-37483595-A-G | not specified | Uncertain significance (Oct 19, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ZC3H12A | protein_coding | protein_coding | ENST00000373087 | 5 | 9828 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.140 | 0.860 | 125730 | 0 | 15 | 125745 | 0.0000596 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.18 | 253 | 371 | 0.681 | 0.0000242 | 3826 |
| Missense in Polyphen | 63 | 137.69 | 0.45754 | 1431 | ||
| Synonymous | -0.448 | 171 | 164 | 1.04 | 0.0000108 | 1301 |
| Loss of Function | 3.30 | 6 | 23.2 | 0.259 | 0.00000140 | 235 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000617 | 0.0000615 |
| Ashkenazi Jewish | 0.000100 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000143 | 0.000105 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay (PubMed:19909337). Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation- related mRNAs, such as IL6 and IL12B, during the early phase of inflammation (PubMed:26320658). Prevents aberrant T-cell-mediated immune reaction by degradation of multiple mRNAs controlling T- cell activation, such as those encoding cytokines (IL6 and IL2), cell surface receptors (ICOS, TNFRSF4 and TNFR2) and transcription factor (REL) (By similarity). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (By similarity). Self regulates by destabilizing its own mRNA (By similarity). Cleaves mRNA harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-dependent manner (PubMed:19909337, PubMed:26320658, PubMed:26134560, PubMed:22561375). Plays a role in the inhibition of microRNAs (miRNAs) biogenesis (PubMed:22055188). Cleaves the terminal loop of a set of precursor miRNAs (pre-miRNAs) important for the regulation of the inflammatory response leading to their degradation, and thus preventing the biosynthesis of mature miRNAs (PubMed:22055188). Plays also a role in promoting angiogenesis in response to inflammatory cytokines by inhibiting the production of antiangiogenic microRNAs via its anti-dicer RNase activity (PubMed:24048733). Affects the overall ubiquitination of cellular proteins (By similarity). Positively regulates deubiquitinase activity promoting the cleavage at 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains on TNF receptor-associated factors (TRAFs), preventing JNK and NF-kappa-B signaling pathway activation, and hence negatively regulating macrophage-mediated inflammatory response and immune homeostasis (By similarity). Induces also deubiquitination of the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A- targeted genes (PubMed:24048733). Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Prevents stress granule (SGs) formation and promotes macrophage apoptosis under stress conditions, including arsenite-induced oxidative stress, heat shock and energy deprivation (By similarity). Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state (By similarity). May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (PubMed:16574901, PubMed:18364357). Functions as a positive regulator of glial differentiation of neuroprogenitor cells through an amyloid precursor protein (APP)-dependent signaling pathway (PubMed:19185603). Attenuates septic myocardial contractile dysfunction in response to lipopolysaccharide (LPS) by reducing I- kappa-B-kinase (IKK)-mediated NF-kappa-B activation, and hence myocardial proinflammatory cytokine production (By similarity). {ECO:0000250|UniProtKB:Q5D1E7, ECO:0000269|PubMed:16574901, ECO:0000269|PubMed:18364357, ECO:0000269|PubMed:19185603, ECO:0000269|PubMed:19909337, ECO:0000269|PubMed:22055188, ECO:0000269|PubMed:22561375, ECO:0000269|PubMed:24048733, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:26134560, ECO:0000269|PubMed:26320658}.; FUNCTION: (Microbial infection) Exhibits antiviral activity against HIV-1 in lymphocytes by decreasing the abundance of HIV-1 viral RNA species. {ECO:0000269|PubMed:24191027}.;
- Disease
- DISEASE: Note=Increased expression of ZC3H12A is associated with ischemic heart disease (PubMed:16574901). {ECO:0000269|PubMed:16574901}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- loftool
- 0.453
- rvis_EVS
- 0.67
- rvis_percentile_EVS
- 84.68
Haploinsufficiency Scores
- pHI
- 0.300
- hipred
- Y
- hipred_score
- 0.662
- ghis
- 0.427
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.920
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Zc3h12a
- Phenotype
- growth/size/body region phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism 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;
Gene ontology
- Biological process
- nuclear-transcribed mRNA catabolic process, endonucleolytic cleavage-dependent decay;angiogenesis;negative regulation of protein phosphorylation;positive regulation of defense response to virus by host;immune response-activating signal transduction;apoptotic process;inflammatory response;cellular response to DNA damage stimulus;nervous system development;regulation of gene expression;positive regulation of autophagy;positive regulation of endothelial cell migration;positive regulation of gene expression;negative regulation of gene expression;negative regulation of muscle cell apoptotic process;positive regulation of lipid storage;positive regulation of cell death;protein deubiquitination;cell differentiation;negative regulation of NF-kappaB transcription factor activity;negative regulation of interleukin-6 production;negative regulation of tumor necrosis factor production;cellular response to oxidative stress;cellular response to glucose starvation;positive regulation of protein import into nucleus;negative regulation of macrophage activation;negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation by host of viral genome replication;negative regulation of nitric oxide biosynthetic process;positive regulation of fat cell differentiation;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;negative regulation of interleukin-1 beta secretion;T cell receptor signaling pathway;protein complex oligomerization;defense response to virus;negative regulation of cardiac muscle contraction;positive regulation of mRNA catabolic process;3'-UTR-mediated mRNA destabilization;cellular response to lipopolysaccharide;cellular response to interleukin-1;cellular response to tumor necrosis factor;RNA phosphodiester bond hydrolysis;RNA phosphodiester bond hydrolysis, endonucleolytic;RNA phosphodiester bond hydrolysis, exonucleolytic;cellular response to virus;negative regulation of cytokine production involved in inflammatory response;positive regulation of execution phase of apoptosis;negative regulation of interleukin-6 secretion;positive regulation of p38MAPK cascade;negative regulation of NIK/NF-kappaB signaling;negative regulation of interferon-gamma secretion;positive regulation of protein deubiquitination;negative regulation of production of miRNAs involved in gene silencing by miRNA;cellular response to sodium arsenite;negative regulation of tumor necrosis factor secretion;cellular response to ionomycin;cellular response to chemokine;negative regulation of T-helper 17 cell differentiation;positive regulation of reactive oxygen species metabolic process;positive regulation of miRNA catabolic process
- Cellular component
- P-body;nucleus;nucleoplasm;cytoplasm;rough endoplasmic reticulum;cytoskeleton;rough endoplasmic reticulum membrane;protein-containing complex;cytoplasmic ribonucleoprotein granule;extrinsic component of endoplasmic reticulum membrane
- Molecular function
- DNA binding;chromatin binding;RNA binding;mRNA binding;mRNA 3'-UTR binding;endoribonuclease activity;exoribonuclease activity;ribonuclease activity;thiol-dependent ubiquitin-specific protease activity;protein binding;miRNA binding;RNA stem-loop binding;mRNA 3'-UTR AU-rich region binding;ribosome binding;metal ion binding