ZFP36L1

Summary

ZFP36L1 (ZFP36 like 1 zinc finger CCCH-type, HGNC:1107) is a protein-coding gene on chromosome 14q24.1, encoding mRNA decay activator protein ZFP36L1 (Q07352). 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. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene is a member of the TIS11 family of early response genes, which are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF. This gene is well conserved across species and has a promoter that contains motifs seen in other early-response genes. 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 677 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte maturation defect 13 (Limited, GenCC)
• GWAS associations: 32
• Clinical variants (ClinVar): 25 total
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_004926

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1107
Approved symbol	ZFP36L1
Name	ZFP36 like 1 zinc finger CCCH-type
Location	14q24.1
Locus type	gene with protein product
Status	Approved
Aliases	Berg36, ERF1, TIS11B, cMG1
Ensembl gene	ENSG00000185650
Ensembl biotype	protein_coding
OMIM	601064
Entrez	677

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000336440, ENST00000439696, ENST00000553375, ENST00000555997, ENST00000557022, ENST00000557086

RefSeq mRNA: 3 — MANE Select: NM_004926 NM_001244698, NM_001244701, NM_004926

CCDS: CCDS9791

Canonical transcript exons

ENST00000439696 — 2 exons

Exon	Start	End
ENSE00002499061	68787662	68790492
ENSE00002530400	68792882	68793067

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9931 / max 108.5483, expressed in 1712 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143832	97.6396	1790
145187	5.9931	1712
143838	3.3932	495
143840	2.6939	1006
145188	1.7437	938
143843	0.8139	221
143836	0.6177	326
143833	0.5640	322
143841	0.4953	280
143834	0.2423	105

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	99.69	gold quality
endocervix	UBERON:0000458	99.54	gold quality
mucosa of stomach	UBERON:0001199	99.49	gold quality
right ovary	UBERON:0002118	99.49	gold quality
ectocervix	UBERON:0012249	99.48	gold quality
nipple	UBERON:0002030	99.47	gold quality
left ovary	UBERON:0002119	99.45	gold quality
urethra	UBERON:0000057	99.44	gold quality
body of uterus	UBERON:0009853	99.44	gold quality
right uterine tube	UBERON:0001302	99.42	gold quality
ventricular zone	UBERON:0003053	99.41	gold quality
skin of abdomen	UBERON:0001416	99.40	gold quality
vagina	UBERON:0000996	99.39	gold quality
superficial temporal artery	UBERON:0001614	99.37	gold quality
ovary	UBERON:0000992	99.33	gold quality
mammary duct	UBERON:0001765	99.33	gold quality
penis	UBERON:0000989	99.28	gold quality
skin of leg	UBERON:0001511	99.28	gold quality
left uterine tube	UBERON:0001303	99.27	gold quality
peritoneum	UBERON:0002358	99.21	gold quality
omental fat pad	UBERON:0010414	99.21	gold quality
popliteal artery	UBERON:0002250	99.20	gold quality
upper leg skin	UBERON:0004262	99.20	gold quality
tibial artery	UBERON:0007610	99.20	gold quality
minor salivary gland	UBERON:0001830	99.19	gold quality
pericardium	UBERON:0002407	99.19	gold quality
epithelium of mammary gland	UBERON:0003244	99.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.19	gold quality
zone of skin	UBERON:0000014	99.17	gold quality
cauda epididymis	UBERON:0004360	99.14	gold quality

Single-cell (SCXA)

Detected in 41 experiment(s), a significant marker in 30.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	5713.10
E-MTAB-10662	yes	3673.59
E-CURD-122	yes	2160.56
E-CURD-84	yes	1033.49
E-GEOD-93593	yes	361.22
E-GEOD-75140	yes	212.71
E-MTAB-10287	yes	73.32
E-MTAB-8410	yes	53.61
E-HCAD-5	yes	52.70
E-HCAD-6	yes	44.26
E-MTAB-6678	yes	40.30
E-HCAD-35	yes	29.58
E-MTAB-9221	yes	28.74
E-GEOD-81547	yes	24.44
E-HCAD-31	yes	23.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
VEGFA	Repression

Upstream regulators (CollecTRI, top): E2F4, FOS, MYC

miRNA regulators (miRDB)

182 targeting ZFP36L1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-33A-5P	99.99	68.62	1055

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 28)

• polymorphisms sequenced in genomic DNA encoding the TTP protein (ZFP36) and those of its two known mammalian relatives, ZFP36L1 and ZFP36L2, from 72 to 92 anonymous human subjects from various geographical and ethnic backgrounds (PMID:14604009)
• Data suggest an important role for butyrate response factor-1 in osteoblasts within the molecular network of parathyroid hormone-dependent bone remodeling. (PMID:15465005)
• Tis11b, an AU-rich binding protein induces apoptosis by rituximab in B cell chronic lymphocytic leukemia cells. (PMID:19092855)
• crystal structures of human and S. pombe eRF1 in complex with eRF3 lacking the GTPase domain revealed details of the interaction between these two factors and marked conformational changes in eRF1 that occur upon binding to eRF3 (PMID:19417105)
• Von Hippel-Lindau gene product modulates TIS11B expression in renal cell carcinoma and has a role in vascular endothelial growth factor expression in hypoxia (PMID:19801654)
• these results suggest an important role of ZFP36L1 in wound healing. (PMID:20166898)
• ZFP36L1 negatively regulates erythroid differentiation by directly binding the 3’ untranslated region of Stat5b encoding mRNA. (PMID:20702587)
• The roles of TTP and BRF proteins in regulated mRNA decay. (PMID:21278925)
• NR4A2 expression is negatively regulated by zinc finger protein 36, C3H1 type-like 1 (Zfp36l1). (PMID:24086717)
• regulator of renal mineralocorticoid receptor abundance (PMID:24700863)
• ZFP36L1 interacts with and mediates degradation of anti-apoptotic BCL2 mRNA as its important target in malignant B-cells. (PMID:25014217)
• Gene expression analysis revealed that three gene BACH2, PTGER4 and ZFP36L1, are down-regulated in MS patients’ blood cells compared to healthy subjects. (PMID:25670004)
• A ZFP36L1-mediated regulatory circuit through repressing CDK6 expression. (PMID:26542173)
• The results indicated that ZFP36L1 and ZFP36L2 play a negative role in cell proliferation; the underlying mechanisms might be mediated through a cyclin D-dependent and p53-independent pathway. (PMID:29426877)
• Study shows that the ZFP36 family member, ZFP36L1, is specifically upregulated in osteoarthritis (OA) chondrocytes and OA cartilage of humans and mice. ZFP36L1 regulates the mRNAs encoding two members of the HSP70 family that appear to exert protective effects on OA pathogenesis by inhibiting chondrocyte apoptosis. (PMID:30622281)
• ZFP36L1 as a novel candidate tumor suppressor gene in myelofibrosis (PMID:30655376)
• Study findings reveal an indispensable role of ZFP36L1 as a posttranscriptional safeguard against aberrant hypoxic signaling and abnormal cell-cycle progression. ZFP36L1 is significantly mutated and underexpressed in bladder cancer and reduction of ZFP36L1 expression was associated with worse survival in patients with breast cancer. (PMID:31551365)
• Overexpression of microRNA-129-5p in glioblastoma inhibits cell proliferation, migration, and colony-forming ability by targeting ZFP36L1. (PMID:31999936)
• ARE-binding protein ZFP36L1 interacts with CNOT1 to directly repress translation via a deadenylation-independent mechanism. (PMID:32311426)
• Zinc finger protein ZFP36L1 inhibits influenza A virus through translational repression by targeting HA, M and NS RNA transcripts. (PMID:32556261)
• Nuclear accumulation of ZFP36L1 is cell cycle-dependent and determined by a C-terminal serine-rich cluster. (PMID:32687160)
• ZFP36L1 plays an ambiguous role in the regulation of cell expansion and negatively regulates CDKN1A in chronic myeloid leukemia cells. (PMID:34090970)
• ZFP36 Family Members Regulate the Proinflammatory Features of Psoriatic Dermal Fibroblasts. (PMID:34333017)
• Zinc Finger Protein ZFP36L1 Inhibits Flavivirus Infection by both 5’-3’ XRN1 and 3’-5’ RNA-Exosome RNA Decay Pathways. (PMID:34643435)
• ZFP36L1 Promotes Gastric Cancer Progression via Regulating JNK and p38 MAPK Signaling Pathways. (PMID:35611776)
• Regulation of neuroendocrine plasticity by the RNA-binding protein ZFP36L1. (PMID:36008402)
• ZFP36 ring finger protein like 1 significantly suppresses human coronavirus OC43 replication. (PMID:36846448)
• MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence. (PMID:38317146)

Cross-species orthologs

23 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfp36l1a	ENSDARG00000016154
danio_rerio	zfp36l1b	ENSDARG00000021443
mus_musculus	Zfp36l1	ENSMUSG00000021127
rattus_norvegicus	Zfp36l1	ENSRNOG00000058646
caenorhabditis_elegans		WBGENE00003230
caenorhabditis_elegans		WBGENE00003231
caenorhabditis_elegans		WBGENE00003388
caenorhabditis_elegans		WBGENE00003864
caenorhabditis_elegans		WBGENE00003865
caenorhabditis_elegans		WBGENE00004078
caenorhabditis_elegans		WBGENE00007961
caenorhabditis_elegans		WBGENE00009532
caenorhabditis_elegans		WBGENE00009537
caenorhabditis_elegans		WBGENE00009539
caenorhabditis_elegans	gla-3	WBGENE00011376
caenorhabditis_elegans		WBGENE00013319
caenorhabditis_elegans		WBGENE00013370
caenorhabditis_elegans		WBGENE00013794
caenorhabditis_elegans		WBGENE00013796
caenorhabditis_elegans		WBGENE00013797
caenorhabditis_elegans		WBGENE00017182
caenorhabditis_elegans		WBGENE00022438
caenorhabditis_elegans		WBGENE00022446

Paralogs (2): ZFP36 (ENSG00000128016), ZFP36L2 (ENSG00000152518)

Protein

Protein identifiers

mRNA decay activator protein ZFP36L1 — Q07352 (reviewed: Q07352)

Alternative names: Butyrate response factor 1, EGF-response factor 1, TPA-induced sequence 11b, Zinc finger protein 36, C3H1 type-like 1

All UniProt accessions (4): G3V2D5, G3V2P5, G3V515, Q07352

UniProt curated annotations — full annotation on UniProt →

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. Acts as a 3’-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Functions by recruiting the CCR4-NOT deadenylase complex and components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes. Also induces the degradation of ARE-containing mRNAs even in absence of poly(A) tail. Binds to 3’-UTR ARE of numerous mRNAs. Positively regulates early adipogenesis by promoting ARE-mediated mRNA decay of immediate early genes (IEGs). Promotes ARE-mediated mRNA decay of mineralocorticoid receptor NR3C2 mRNA in response to hypertonic stress. Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA. Positively regulates monocyte/macrophage cell differentiation by promoting ARE-mediated mRNA decay of the cyclin-dependent kinase CDK6 mRNA. Promotes degradation of ARE-containing pluripotency-associated mRNAs in embryonic stem cells (ESCs), such as NANOG, through a fibroblast growth factor (FGF)-induced MAPK-dependent signaling pathway, and hence attenuates ESC self-renewal and positively regulates mesendoderm differentiation. May play a role in mediating pro-apoptotic effects in malignant B-cells by promoting ARE-mediated mRNA decay of BCL2 mRNA. In association with ZFP36L2 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 and functional immune cell formation. Together with ZFP36L2 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. Participates in the delivery of target ARE-mRNAs to processing bodies (PBs). In addition to its cytosolic mRNA-decay function, plays a role in the regulation of nuclear mRNA 3’-end processing; modulates mRNA 3’-end maturation efficiency of the DLL4 mRNA through binding with an ARE embedded in a weak noncanonical polyadenylation (poly(A)) signal in endothelial cells. Also involved in the regulation of stress granule (SG) and P-body (PB) formation and fusion. Plays a role in vasculogenesis and endocardial development. Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis. Plays a role in myoblast cell differentiation.

Subunit / interactions. Associates with the cytoplasmic CCR4-NOT deadenylase and RNA exosome complexes to trigger ARE-containing mRNA deadenylation and decay processes. Interacts with CNOT1. Interacts (via N-terminus) with CNOT6. Interacts with CNOT7; this interaction is inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner. Interacts with DCP1A. Interacts (via N-terminus) with DCP2. Interacts (via N-terminus) with EXOSC2. Interacts with XRN1. Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner. Interacts (via phosphorylated form) with YWHAZ; this interaction occurs in a p38 MAPK- and AKT-signaling pathways.

Subcellular location. Nucleus. Cytoplasm. Cytoplasmic granule. P-body.

Tissue specificity. Expressed mainly in the basal epidermal layer, weakly in the suprabasal epidermal layers. Expressed in epidermal keratinocytes (at protein level). Expressed in osteoblasts.

Post-translational modifications. Phosphorylated. Phosphorylated by RPS6KA1 at Ser-334 upon phorbol 12-myristate 13-acetate (PMA) treatment; this phosphorylation results in dissociation of the CCR4-NOT deadenylase complex and induces p38 MAPK-mediated stabilization of the low-density lipoprotein receptor LDLR mRNA. Phosphorylated by protein kinase AKT1 at Ser-92 and Ser-203 in response to insulin; these phosphorylations stabilize ZFP36L1, increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization. AKT1-mediated phosphorylation at Ser-92 does not impair ARE-containing RNA-binding. Phosphorylated at Ser-54, Ser-92 and Ser-203 by MAPKAPK2; these phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization in a protein kinase AKT1-independent manner. MAPKAPK2-mediated phosphorylations at Ser-54, Ser-92 and Ser-203 do not impair ARE-containing RNA-binding. Phosphorylations increase the association with 14-3-3 proteins and mediate ARE-containing mRNA stabilization during early adipogenesis in a p38 MAPK- and AKT-dependent manner. Ubiquitinated. Ubiquitination leads to proteasomal degradation, a process inhibited by phosphorylations at Ser-90, Ser-92 and Ser-203.

Induction. Down-regulated under hypoxic conditions in endothelial cells (at protein level). Up-regulated by growth factor (TGF-beta), cytokines, tumor necrosis factor (TNF) and epidermal growth factor (EGF) in keratinocytes. Up-regulated also by glucocorticoid dexamethasone in keratinocytes. Up-regulated in keratinocytes in response to wounding in a p38 MAPK-dependent manner. Up-regulated by the parathyroid hormone (PTH) in osteoblast-like cells in a cAMP/PKA-dependent manner. Up-regulated in response to adrenocorticotropic hormone (ACTH). Up-regulated during monocyte/macrophage differentiation in response to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Down-regulated by butyrate in colorectal cancer cells.

RefSeq proteins (3): NP_001231627, NP_001231630, NP_004917* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR007635	Tis11B_N	Domain
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR045877	ZFP36-like	Family

Pfam: PF00642, PF04553

UniProt features (23 total): mutagenesis site 8, modified residue 6, region of interest 4, zinc finger region 2, chain 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1W0W	X-RAY DIFFRACTION	2.11
1W0V	X-RAY DIFFRACTION	2.27

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07352-F1	59.70	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 92, 203, 318, 334, 54, 90

Mutagenesis-validated functional residues (8):

Position	Phenotype
54	inhibits mapkapk2-mediated are-containing mrna stabilization; when associated with a-92 and a-203.
90	inhibits interaction with 14-3-3 proteins and akt1-mediated are-containing mrna stabilization, but does not affect are b
92	inhibits mapkapk2-mediated are-containing mrna stabilization; when associated with a-54 and a-203. inhibits interaction
120	reduces binding to are-containing mrnas and are-mediated mrna decay. inhibits binding to are-containing mrnas and are-me
158	reduces binding to are-containing mrnas and are-mediated mrna decay. inhibits binding to are-containing mrnas and are-me
203	inhibits interaction with 14-3-3 proteins and akt1-mediated are-containing mrna stabilization; when associated with a-92
334	inhibits p38 mapk-mediated ldlr mrna stabilization, but does not inhibit interaction with cnot1 and cnot7; when associat
336	inhibits p38 mapk-mediated ldlr mrna stabilization, but does not inhibit interaction with cnot1 and cnot7; when associat

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA

MSigDB gene sets: 1026 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, YAATNRNNNYNATT_UNKNOWN, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, WANG_CLIM2_TARGETS_UP, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, MYOGENIN_Q6, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS

GO Biological Process (48): MAPK cascade (GO:0000165), nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288), vasculogenesis (GO:0001570), proepicardium development (GO:0003342), mRNA processing (GO:0006397), regulation of translation (GO:0006417), apoptotic process (GO:0006915), heart development (GO:0007507), cell population proliferation (GO:0008283), response to wounding (GO:0009611), regulation of gene expression (GO:0010468), regulation of keratinocyte proliferation (GO:0010837), neural tube development (GO:0021915), nuclear-transcribed mRNA catabolic process, deadenylation-independent decay (GO:0031086), regulation of mRNA 3’-end processing (GO:0031440), cellular response to insulin stimulus (GO:0032869), T cell differentiation in thymus (GO:0033077), multicellular organism growth (GO:0035264), p38MAPK cascade (GO:0038066), regulation of mRNA stability (GO:0043488), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), cellular response to fibroblast growth factor stimulus (GO:0044344), regulation of B cell differentiation (GO:0045577), positive regulation of fat cell differentiation (GO:0045600), regulation of keratinocyte differentiation (GO:0045616), negative regulation of erythrocyte differentiation (GO:0045647), positive regulation of monocyte differentiation (GO:0045657), regulation of myoblast differentiation (GO:0045661), mesendoderm development (GO:0048382), mRNA transport (GO:0051028), chorio-allantoic fusion (GO:0060710), 3’-UTR-mediated mRNA destabilization (GO:0061158), ERK1 and ERK2 cascade (GO:0070371), cellular response to cAMP (GO:0071320), cellular response to tumor necrosis factor (GO:0071356), cellular response to epidermal growth factor stimulus (GO:0071364), cellular response to peptide hormone stimulus (GO:0071375), cellular response to glucocorticoid stimulus (GO:0071385), cellular response to hypoxia (GO:0071456), cellular response to salt stress (GO:0071472)

GO Molecular Function (8): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA binding (GO:0003729), zinc ion binding (GO:0008270), mRNA 3’-UTR AU-rich region binding (GO:0035925), 14-3-3 protein binding (GO:0071889), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): P-body (GO:0000932), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of mRNA stability by proteins that bind AU-rich elements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear-transcribed mRNA catabolic process	2
nucleic acid binding	2
cellular anatomical structure	2
intracellular signaling cassette	1
mRNA destabilization	1
cell differentiation	1
blood vessel morphogenesis	1
septum transversum development	1
mesenchyme development	1
RNA processing	1
mRNA metabolic process	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
animal organ development	1
circulatory system development	1
cellular process	1
response to stress	1
gene expression	1
regulation of macromolecule biosynthetic process	1
keratinocyte proliferation	1
regulation of epithelial cell proliferation	1
nervous system development	1
tube development	1
chordate embryonic development	1
epithelium development	1
mRNA 3’-end processing	1
regulation of mRNA processing	1
response to insulin	1
cellular response to peptide hormone stimulus	1
T cell differentiation	1
multicellular organismal process	1
developmental growth	1
MAPK cascade	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
RNA binding	1

Protein interactions and networks

STRING

1622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFP36L1	DCP2	Q8IU60	791
ZFP36L1	ELAVL1	Q15717	743
ZFP36L1	UPF1	Q92900	731
ZFP36L1	XRN1	Q8IZH2	703
ZFP36L1	MAPKAPK2	P49137	691
ZFP36L1	CNOT1	A5YKK6	686
ZFP36L1	SMG1	Q96Q15	632
ZFP36L1	CNOT7	Q9UIV1	615
ZFP36L1	HNRNPD	P07029	591
ZFP36L1	KHSRP	Q92945	510
ZFP36L1	EXOSC2	Q13868	509
ZFP36L1	XPO1	O14980	505
ZFP36L1	CD47	Q08722	492
ZFP36L1	ZNF318	Q5VUA4	466
ZFP36L1	RAD51B	O15315	465

IntAct

36 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
ZFP36L1	YWHAG	psi-mi:“MI:0915”(physical association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
YWHAZ	ZFP36L1	psi-mi:“MI:0914”(association)	0.530
ZFP36L1	MAPK14	psi-mi:“MI:0915”(physical association)	0.510
MAPK14	ZFP36L1	psi-mi:“MI:0915”(physical association)	0.510
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
TERF1	ZFP36L1	psi-mi:“MI:0915”(physical association)	0.370
TINF2	ZFP36L1	psi-mi:“MI:0915”(physical association)	0.370
ZFP36L1	ACD	psi-mi:“MI:0915”(physical association)	0.370
ZFP36L1	POT1	psi-mi:“MI:0915”(physical association)	0.370
ZFP36L1	TFAP2C	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
ZFP36L1	DECR1	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
ZFP36L1	CNOT1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (45): MAPK14 (Two-hybrid), MAPK14 (Affinity Capture-Western), ZFP36L1 (Affinity Capture-MS), ZFP36L1 (Biochemical Activity), CNOT6 (Affinity Capture-Western), DCP2 (Affinity Capture-Western), EXOSC2 (Affinity Capture-Western), ZFP36L1 (Affinity Capture-MS), ZFP36L1 (Affinity Capture-MS), ZFP36L1 (Two-hybrid), ZFP36L1 (Affinity Capture-MS), KLHL23 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), ZFP36L1 (Affinity Capture-MS), ZFP36L1 (Affinity Capture-MS)

ESM2 similar proteins: A2WSZ6, A2YX04, A2ZVY5, B8AWM1, B8B0R8, B8BF91, P16046, P48000, P48001, Q05A36, Q07352, Q0E3C3, Q0JEE2, Q0VDT2, Q10EC6, Q10ED2, Q10EL1, Q2QPW2, Q3UE17, Q567C6, Q5JLR7, Q5U2Z0, Q5U5Q3, Q5VM82, Q5VR07, Q5W6D6, Q688R3, Q6AWX7, Q6EPZ0, Q6EPZ2, Q6IEK5, Q6IEN1, Q6L4N4, Q6L5G1, Q6Z528, Q6Z869, Q6Z8M8, Q6ZBS8, Q6ZK57, Q75LX7

Diamond homologs: A2ZVY5, A4IIN5, G5EC86, G5EF15, P17431, P22893, P23949, P23950, P26651, P47973, P47974, P47976, P47977, P47979, P47980, P53781, Q07352, Q10MN8, Q23359, Q5ISE2, Q5PP65, Q6L5G1, Q6S9E0, Q7ZXW9, Q805B4, Q84UQ3, Q9C7C3, Q9C9F5, Q9C9N3, Q9FG30, Q9LQM3, Q9LT81, Q9XV46, Q57W26, Q7F8R0, Q8L7S3, Q94131, Q69XQ3, Q7XPK1, Q5VR07

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
AKT1	down-regulates	ZFP36L1	phosphorylation
MAPKAPK2	down-regulates	ZFP36L1	phosphorylation
AKT	down-regulates	ZFP36L1	phosphorylation
RPS6KA1	“down-regulates activity”	ZFP36L1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	205.0×	1e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	180.9×	2e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	180.9×	2e-13
Activation of BH3-only proteins	7	133.7×	2e-12
RHO GTPases activate PKNs	7	85.4×	5e-11
Intrinsic Pathway for Apoptosis	7	78.8×	8e-11
FOXO-mediated transcription	5	64.6×	1e-07
SARS-CoV-1-host interactions	7	47.3×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	67.8×	9e-07
intracellular protein localization	7	27.1×	7e-07

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — BLCA, MLYM.

Clinical variants and AI predictions

ClinVar

25 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4669 predictions. Top by Δscore:

Variant	Effect	Δscore
14:105211118:CCAC:C	donor_loss	1.0000
14:105211119:CA:C	donor_loss	1.0000
14:105211166:T:TA	donor_gain	1.0000
14:105211169:T:TA	donor_gain	1.0000
14:105217611:T:TA	donor_gain	1.0000
14:105217801:C:CC	acceptor_gain	1.0000
14:105217802:T:C	acceptor_gain	1.0000
14:105217802:T:TC	acceptor_gain	1.0000
14:105218993:CCCA:C	donor_loss	1.0000
14:105218994:CCA:C	donor_loss	1.0000
14:105218996:ACCT:A	donor_loss	1.0000
14:105218997:C:CT	donor_loss	1.0000
14:105219051:TTT:T	acceptor_gain	1.0000
14:105219052:TT:T	acceptor_gain	1.0000
14:105219054:C:CC	acceptor_gain	1.0000
14:105219145:GCTTA:G	donor_loss	1.0000
14:105219146:CTTAC:C	donor_loss	1.0000
14:105219147:TTACC:T	donor_loss	1.0000
14:105219148:TA:T	donor_loss	1.0000
14:105219149:A:AC	donor_gain	1.0000
14:105219149:AC:A	donor_gain	1.0000
14:105219149:ACC:A	donor_gain	1.0000
14:105219150:C:A	donor_loss	1.0000
14:105219150:C:CC	donor_gain	1.0000
14:105219150:CC:C	donor_gain	1.0000
14:105219150:CCC:C	donor_gain	1.0000
14:105219150:CCCCT:C	donor_gain	1.0000
14:105219231:TA:T	acceptor_gain	1.0000
14:105219233:C:CC	acceptor_gain	1.0000
14:105219242:C:CT	acceptor_gain	1.0000

AlphaMissense

2213 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:68789560:G:C	F330L	1.000
14:68789560:G:T	F330L	1.000
14:68789561:A:C	F330C	1.000
14:68789561:A:G	F330S	1.000
14:68789562:A:G	F330L	1.000
14:68789564:A:G	I329T	1.000
14:68789564:A:T	I329N	1.000
14:68789570:A:G	L327P	1.000
14:68789570:A:T	L327Q	1.000
14:68790019:G:C	H177Q	1.000
14:68790019:G:T	H177Q	1.000
14:68790020:T:A	H177L	1.000
14:68790020:T:C	H177R	1.000
14:68790021:G:A	H177Y	1.000
14:68790021:G:C	H177D	1.000
14:68790021:G:T	H177N	1.000
14:68790023:A:T	I176N	1.000
14:68790025:G:C	F175L	1.000
14:68790025:G:T	F175L	1.000
14:68790026:A:C	F175C	1.000
14:68790026:A:G	F175S	1.000
14:68790027:A:C	F175V	1.000
14:68790027:A:G	F175L	1.000
14:68790027:A:T	F175I	1.000
14:68790028:G:C	H174Q	1.000
14:68790028:G:T	H174Q	1.000
14:68790029:T:C	H174R	1.000
14:68790030:G:C	H174D	1.000
14:68790031:G:C	C173W	1.000
14:68790032:C:A	C173F	1.000

dbSNP variants (sampled 300 via entrez): RS1000267514 (14:68794603 A>G,T), RS1000399122 (14:68788530 C>G,T), RS1000478834 (14:68787684 T>C), RS1000577039 (14:68794756 T>C,G), RS1000850905 (14:68787924 G>A,T), RS1000947556 (14:68792948 T>C), RS1001003729 (14:68793440 G>A,C,T), RS1001328205 (14:68797920 A>G), RS1001737645 (14:68793958 C>T), RS1002638012 (14:68796613 G>T), RS1002776263 (14:68792378 G>A), RS1003253926 (14:68796723 T>C), RS1003736220 (14:68796462 C>T), RS1003773400 (14:68791005 C>G,T), RS1003962663 (14:68788211 A>G)

Disease associations

OMIM: gene MIM:601064 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte maturation defect 13	Limited	Autosomal recessive

Mondo (1): oocyte maturation defect 13 (MONDO:0859330)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000612_14	Celiac disease	4.000000e-07
GCST000879_4	Crohn’s disease	2.000000e-10
GCST001198_40	Multiple sclerosis	9.000000e-12
GCST001725_22	Inflammatory bowel disease	3.000000e-10
GCST001942_16	Prostate cancer	3.000000e-10
GCST003194_21	Fibrinogen levels	2.000000e-12
GCST004121_5	Fibrinogen levels	4.000000e-13
GCST004122_7	Fibrinogen levels	8.000000e-14
GCST005523_33	Celiac disease	5.000000e-08
GCST005528_23	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	1.000000e-08
GCST005531_59	Multiple sclerosis	3.000000e-12
GCST006586_33	Urinary albumin excretion	6.000000e-09
GCST006627_3	Diastolic blood pressure	4.000000e-11
GCST006988_26	Blond vs. brown/black hair color	7.000000e-12
GCST008489_7	Celiac disease	3.000000e-08
GCST008790_46	Urinary albumin-to-creatinine ratio	7.000000e-12
GCST008791_11	Microalbuminuria	6.000000e-09
GCST008794_37	Urinary albumin-to-creatinine ratio	1.000000e-11
GCST009357_8	Nonsyndromic cleft lip	6.000000e-06
GCST009391_1285	Metabolite levels	6.000000e-08
GCST009640_21	Urinary albumin-to-creatinine ratio	6.000000e-09
GCST009798_33	Asthma	7.000000e-13
GCST010241_65	Apolipoprotein A1 levels	4.000000e-14
GCST010242_322	HDL cholesterol levels	1.000000e-13
GCST010304_3	Cutaneous malignant melanoma	3.000000e-06
GCST011389_6	Rheumatoid arthritis	3.000000e-08
GCST90002383_260	Hematocrit	2.000000e-09
GCST90002384_342	Hemoglobin	8.000000e-10
GCST90002397_363	Mean spheric corpuscular volume	2.000000e-12
GCST90010715_16	Arthritis (juvenile idiopathic)	1.000000e-08

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004285	albuminuria
EFO:0006336	diastolic blood pressure
EFO:0003924	hair color
EFO:0007778	urinary albumin to creatinine ratio
EFO:0003959	cleft lip
EFO:0010548	xanthine measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

84 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, affects binding, decreases expression	6
sodium arsenite	decreases expression, increases abundance, increases expression	4
Cisplatin	affects cotreatment, decreases expression, increases response to substance	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
nickel sulfate	decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Ethyl Methanesulfonate	decreases expression, increases expression	2
Lipopolysaccharides	decreases expression, affects expression, affects response to substance, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
titanium dioxide	increases methylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
nickel subsulfide	decreases expression	1
cobaltous chloride	decreases expression	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
ferrous chloride	increases expression	1
cupric chloride	increases expression	1
cupric oxide	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.