GeneBe

ZFP36L2

protein-coding

ZFP36 ring finger protein like 2, the group of Zinc fingers CCCH-type

Gene summary

This gene is a member of the TIS11 family of early response genes. Family members are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF. The encoded protein contains a distinguishing putative zinc finger domain with a repeating cys-his motif. This putative nuclear transcription factor most likely functions in regulating the response to growth factors. [provided by RefSeq, Jul 2008]

Previous symbols:
  • BRF2

MANE transcript

NM_006887.5

Inheritance

AR

ClinVar variants

U:111B:16

Top phenotype

Oocyte/zygote/embryo maturation arrest 13

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr2:43,222,402-43,226,606

External References & Databases

Ensembl (ENSG00000152518)NCBI Gene (678)OMIM (612053)HGNC:1108GenCCUniProt (P47974)AlphaFoldClinVar (ZFP36L2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~4.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oocyte maturation defect 13LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859330

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Oocyte/zygote/embryo maturation arrest 13AR

Manifestation: Obstetric

Intervention: General

Rationale: 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

Refs: 34611029Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZFP36L2 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 112
ZFP36L2-related disorderTotal: 9
not providedTotal: 5
Oocyte maturation defect 13Total: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006887.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
12
clinvar
 12
missense
110
clinvar
2
clinvar
2
clinvar
 114
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
0
Total00111142127

Highest pathogenic variant AF is 0.00014250782

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006887.5RefSeqNP_008818.32MANE Select
ENST00000282388.4EnsemblENSP00000282388.32MANE Select
ENST00000929033.1EnsemblENSP00000599092.12Standard
ENST00000929033.2EnsemblENSP00000599092.12Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Cellular senescence - Homo sapiens (human)
  • Preimplantation Embryo
  • TYROBP Causal Network

Biological Process

  • nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
  • regulation of transcription by RNA polymerase II
  • mRNA catabolic process
  • cell population proliferation
  • response to wounding

Molecular Function

  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • DNA binding
  • DNA-binding transcription factor activity
  • RNA binding
  • mRNA 3'-UTR binding

Cellular Component

  • nucleus
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000282388
Coding exons
2
Length
4208
Individuals with no LoFs
124191
Homozygous LoFs
0
Heterozygous LoFs
6
Defined
124197
p
0.0000242
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-1.843322501.330.00001173061
Missense (PolyPhen)8572.2751.1761761
Synonymous-8.282371211.960.000005901046
Loss of Function3.00010.50.004.56e-7123

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.000100.00010rare
East Asian00.0absent
Finnish0.0000870.000048rare
European (Non-Finnish)0.0000380.000036rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:25106868, PubMed:14981510). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:25106868). Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes (PubMed:25106868). Binds to 3'-UTR ARE of numerous mRNAs (PubMed:20506496, PubMed:25106868, PubMed:14981510). Promotes ARE- containing mRNA decay of the low-density lipoprotein (LDL) receptor (LDLR) mRNA in response to phorbol 12-myristate 13- acetate (PMA) treatment in a p38 MAPK-dependent manner (PubMed:25106868). Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Plays a role in mature peripheral neuron integrity by promoting ARE-containing mRNA decay of the transcriptional repressor REST mRNA. Plays a role in ovulation and oocyte meiotic maturation by promoting ARE-mediated mRNA decay of the luteinizing hormone receptor LHCGR mRNA. Acts as a negative regulator of erythroid cell differentiation: promotes glucocorticoid-induced self-renewal of erythroid cells by binding mRNAs that are induced or highly expressed during terminal erythroid differentiation and promotes their degradation, preventing erythroid cell differentiation. In association with ZFP36L1 maintains quiescence on developing B lymphocytes by promoting ARE-mediated decay of several mRNAs encoding cell cycle regulators that help B cells progress through the cell cycle, and hence ensuring accurate variable-diversity- joining (VDJ) recombination process and functional immune cell formation. Together with ZFP36L1 is also necessary for thymocyte development and prevention of T-cell acute lymphoblastic leukemia (T-ALL) transformation by promoting ARE-mediated mRNA decay of the oncogenic transcription factor NOTCH1 mRNA. {ECO:0000250|UniProtKB:P23949, ECO:0000269|PubMed:14981510, ECO:0000269|PubMed:20506496, ECO:0000269|PubMed:25106868}.;
Disease
DISEASE: Note=Defects in ZFP36L2 may be a cause of leukemias. Frameshfits mutations disrupting ZFP36L2 have been found in a patient with acute myeloid leukemia (PubMed:21109922). {ECO:0000269|PubMed:21109922}.;

Recessive Scores

pRec
0.111

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.903

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.