ZFP36L2

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

Basic information

Region (hg38): 2:43222402-43226606

Previous symbols: [ "BRF2" ]

Links

ENSG00000152518 ∙ NCBI:678 ∙ OMIM:612053 ∙ HGNC:1108 ∙ Uniprot:P47974 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oocyte maturation defect 13 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 13	AR	General	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	Obstetric	34611029

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFP36L2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFP36L2 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				7	2	9
missense			41	2	3	46
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	41	9	5

Variants in ZFP36L2

This is a list of pathogenic ClinVar variants found in the ZFP36L2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-43224377-C-CT			not provided (-)
2-43224423-T-G		not specified	Uncertain significance (Dec 01, 2022)
2-43224463-G-A			Likely benign (Nov 01, 2024)
2-43224514-G-C		not specified	Uncertain significance (Jan 09, 2024)
2-43224534-G-A		not specified	Uncertain significance (Dec 13, 2023)
2-43224546-C-G		not specified	Uncertain significance (Mar 06, 2023)
2-43224570-G-A		not specified	Uncertain significance (Jun 04, 2024)
2-43224572-G-A		not specified	Uncertain significance (Aug 02, 2022)
2-43224577-C-T		ZFP36L2-related disorder	Likely benign (Dec 26, 2019)
2-43224599-C-A		not specified	Uncertain significance (May 31, 2023)
2-43224616-C-G		not specified	Uncertain significance (Aug 30, 2022)
2-43224627-G-A		not specified	Uncertain significance (Feb 16, 2023)
2-43224634-G-A		ZFP36L2-related disorder	Likely benign (Jul 12, 2019)
2-43224644-G-A		not specified	Uncertain significance (Feb 14, 2023)
2-43224675-C-G		not specified	Uncertain significance (Nov 30, 2022)
2-43224681-G-A		not specified	Uncertain significance (Mar 15, 2024)
2-43224713-G-A		not specified	Uncertain significance (Dec 01, 2022)
2-43224714-C-T		not specified	Uncertain significance (Nov 08, 2022)
2-43224737-G-A		not specified	Uncertain significance (Jan 23, 2023)
2-43224753-C-A		not specified	Uncertain significance (Feb 10, 2022)
2-43224761-G-T		not specified	Uncertain significance (Feb 22, 2023)
2-43224763-C-T			Likely benign (Jun 01, 2022)
2-43224794-G-T		not specified	Uncertain significance (Jun 10, 2024)
2-43224815-G-A		not specified	Uncertain significance (May 26, 2023)
2-43224818-G-A		ZFP36L2-related disorder	Benign (Jan 08, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFP36L2	protein_coding	protein_coding	ENST00000282388	2	4208

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.966	0.0339	124191	0	6	124197	0.0000242

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.84	332	250	1.33	0.0000117	3061
Missense in Polyphen		85	72.275	1.1761		761
Synonymous	-8.28	237	121	1.96	0.00000590	1046
Loss of Function	3.00	0	10.5	0.00	4.56e-7	123

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000102	0.000100
East Asian	0.00	0.00
Finnish	0.0000871	0.0000484
European (Non-Finnish)	0.0000375	0.0000356
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Cellular senescence - Homo sapiens (human);Preimplantation Embryo;TYROBP Causal Network (Consensus)

Recessive Scores

• pRec: 0.111

Haploinsufficiency Scores

• pHI: 0.629
• hipred: N
• hipred_score: 0.399
• ghis: 0.619

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Zfp36l2
• Phenotype: renal/urinary system phenotype; immune system phenotype; digestive/alimentary phenotype; neoplasm; 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); hematopoietic system phenotype; 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); liver/biliary system phenotype; embryo phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• 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;hemopoiesis;T cell differentiation in thymus;somatic stem cell population maintenance;regulation of mRNA stability;cellular response to fibroblast growth factor stimulus;regulation of B cell differentiation;negative regulation of fat cell differentiation;somatic stem cell division;definitive hemopoiesis;3'-UTR-mediated mRNA destabilization;ERK1 and ERK2 cascade;cellular response to tumor necrosis factor;cellular response to epidermal growth factor stimulus;cellular response to glucocorticoid stimulus;cellular response to transforming growth factor beta stimulus;cellular response to granulocyte macrophage colony-stimulating factor stimulus;positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay;negative regulation of mitotic cell cycle phase transition;negative regulation of stem cell differentiation
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;RNA binding;mRNA 3'-UTR binding;protein binding;AU-rich element binding;mRNA 3'-UTR AU-rich region binding;metal ion binding