ZAR1L

Summary

ZAR1L (zygote arrest 1 like, HGNC:37116) is a protein-coding gene on chromosome 13q13.1, encoding Protein ZAR1-like (A6NP61). mRNA-binding protein required for maternal mRNA storage, translation and degradation during oocyte maturation.

This gene encodes a member of the ZAR1 family that is predominantly expressed in oocytes and early embryos. The protein may function as an RNA regulator in early embryos.

Source: NCBI Gene 646799 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_001136571

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37116
Approved symbol	ZAR1L
Name	zygote arrest 1 like
Location	13q13.1
Locus type	gene with protein product
Status	Approved
Aliases	Z3CXXC7
Ensembl gene	ENSG00000189167
Ensembl biotype	protein_coding
OMIM	620424
Entrez	646799

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000345108, ENST00000533490

RefSeq mRNA: 1 — MANE Select: NM_001136571 NM_001136571

CCDS: CCDS45023

Canonical transcript exons

ENST00000533490 — 6 exons

Exon	Start	End
ENSE00001365416	32308686	32308760
ENSE00001380497	32303699	32304022
ENSE00001385658	32310639	32310731
ENSE00002140998	32311272	32312093
ENSE00002167541	32315315	32315363
ENSE00002196734	32314330	32314550

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 85.60.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1654 / max 17.7053, expressed in 59 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136703	0.0909	39
136704	0.0746	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.23	gold quality
bone marrow cell	CL:0002092	45.30	gold quality
bone marrow	UBERON:0002371	44.47	gold quality
granulocyte	CL:0000094	43.60	silver quality
right testis	UBERON:0004534	40.93	gold quality
testis	UBERON:0000473	40.74	gold quality
left testis	UBERON:0004533	40.35	gold quality
sural nerve	UBERON:0015488	38.59	gold quality
lymph node	UBERON:0000029	37.72	silver quality
hindlimb stylopod muscle	UBERON:0004252	37.58	silver quality
ganglionic eminence	UBERON:0004023	37.49	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
skeletal muscle tissue	UBERON:0001134	34.83	gold quality
leukocyte	CL:0000738	34.82	gold quality
monocyte	CL:0000576	34.65	gold quality
mucosa of stomach	UBERON:0001199	34.04	gold quality
right uterine tube	UBERON:0001302	33.83	gold quality
prefrontal cortex	UBERON:0000451	33.61	silver quality
muscle tissue	UBERON:0002385	33.36	gold quality
calcaneal tendon	UBERON:0003701	33.17	gold quality
fallopian tube	UBERON:0003889	31.53	gold quality
right lobe of liver	UBERON:0001114	31.44	silver quality
descending thoracic aorta	UBERON:0002345	31.28	silver quality
ascending aorta	UBERON:0001496	30.93	silver quality
thoracic aorta	UBERON:0001515	30.86	silver quality
right ovary	UBERON:0002118	30.53	silver quality
right coronary artery	UBERON:0001625	30.27	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ZAR1L, 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-548AW	99.99	72.57	3559
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-495-5P	97.62	68.28	682

Literature-anchored findings (GeneRIF, showing 1)

• BRCA2 gene promoter has bi-directional activity, expressing BRCA2 and a novel C4-type zinc finger containing transcription factor ZAR2. (PMID:20202217)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zar1l	ENSDARG00000055973
mus_musculus	Zar1l	ENSMUSG00000056586
rattus_norvegicus	Zar1l	ENSRNOG00000051294

Paralogs (1): ZAR1 (ENSG00000182223)

Protein

Protein identifiers

Protein ZAR1-like — A6NP61 (reviewed: A6NP61)

Alternative names: Zygote arrest protein 1-like

All UniProt accessions (1): A6NP61

UniProt curated annotations — full annotation on UniProt →

Function. mRNA-binding protein required for maternal mRNA storage, translation and degradation during oocyte maturation. Probably promotes formation of some phase-separated membraneless compartment that stores maternal mRNAs in oocytes: acts by undergoing liquid-liquid phase separation upon binding to maternal mRNAs. Binds to the 3’-UTR of maternal mRNAs, inhibiting their translation.

Subunit / interactions. Interacts with YBX2.

Subcellular location. Cytoplasm. Cytoplasmic ribonucleoprotein granule.

Domain organisation. Disordered region at the N-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of membraneless compartments that store maternal mRNAs in oocytes. The 3CxxC-type mediates binding to the 3’-UTR of mRNAs.

Similarity. Belongs to the ZAR1 family.

RefSeq proteins (1): NP_001130043* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026775	Zar1	Family
IPR027377	ZAR1/RTP1-5-like_Znf-3CxxC	Domain

Pfam: PF13695

UniProt features (4 total): chain 1, zinc finger region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NP61-F1	59.00	0.13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_OOGENESIS, chr13q13, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_MATURATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_OOCYTE_MATURATION, GOBP_OOCYTE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_REGULATION_OF_TRANSLATION, GOCC_RIBONUCLEOPROTEIN_GRANULE

GO Biological Process (5): oocyte maturation (GO:0001556), translation (GO:0006412), negative regulation of translation (GO:0017148), cell differentiation (GO:0030154), oogenesis (GO:0048477)

GO Molecular Function (5): mRNA 3’-UTR binding (GO:0003730), zinc ion binding (GO:0008270), RNA binding (GO:0003723), mRNA binding (GO:0003729), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), cytoplasmic ribonucleoprotein granule (GO:0036464), intracellular membraneless organelle (GO:0043232)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
developmental process involved in reproduction	1
cell maturation	1
oocyte development	1
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
cellular developmental process	1
germ cell development	1
female gamete generation	1
mRNA binding	1
transition metal ion binding	1
nucleic acid binding	1
RNA binding	1
cation binding	1
cellular anatomical structure	1
cytoplasm	1
ribonucleoprotein granule	1
membraneless organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZAR1L	ZNF879	B4DU55	584
ZAR1L	BTG4	Q9NY30	445
ZAR1L	NPM2	Q86SE8	431
ZAR1L	ZNF596	Q8TC21	431
ZAR1L	WEE2	P0C1S8	412
ZAR1L	ZNF385B	Q569K4	348
ZAR1L	CPEB1	Q9BZB8	344
ZAR1L	HELB	Q8NG08	311
ZAR1L	CPEB4	Q17RY0	294
ZAR1L	TEX9	Q8N6V9	284
ZAR1L	SLC10A4	Q96EP9	283
ZAR1L	YBX2	Q9Y2T7	270
ZAR1L	PABPC1L	Q4VXU2	269
ZAR1L	BRCA2	P51587	255
ZAR1L	BRS3	P32247	246

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ZAR1L	BCL2L11	psi-mi:“MI:0914”(association)	0.530

BioGRID (16): FAM83D (Affinity Capture-MS), MCL1 (Affinity Capture-MS), CLUH (Affinity Capture-MS), ANGEL1 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), FAM73A (Affinity Capture-MS), PXN (Affinity Capture-MS), FAM117A (Affinity Capture-MS), GLCCI1 (Affinity Capture-MS), BCL2L1 (Affinity Capture-MS), HMBOX1 (Affinity Capture-MS), BCL2L11 (Affinity Capture-MS), GPHN (Affinity Capture-MS), EML3 (Affinity Capture-MS), ELAVL2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A4QP16, A6NP61, B2RVL6, C0SPG1, C3VD30, K7SGN7, O54880, P56163, Q1XFL1, Q29RJ0, Q2KI52, Q32L09, Q3V0J4, Q4R2Y2, Q4R739, Q58D79, Q5RAK6, Q5TKR9, Q5VWQ0, Q6PDK8, Q768S4, Q7T3T8, Q7T3T9, Q80T69, Q86US8, Q86Y01, Q8AW93, Q8BMD7, Q8BRB7, Q8BZ21, Q8CAK3, Q8CDN1, Q8HXK7, Q8K3Y6, Q8N2G6, Q8N9V6, Q8TE76

Diamond homologs: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, C0SPG1, C3VD30, K7SGN7, Q1XFL1, Q7T3T8, Q7T3T9, Q7T3U0, Q7TSX9, Q80SU3, Q86SH2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

746 predictions. Top by Δscore:

Variant	Effect	Δscore
13:32304025:T:C	acceptor_gain	0.9900
13:32310732:C:CC	acceptor_gain	0.9900
13:32315088:G:C	donor_gain	0.9900
13:32315136:C:A	donor_gain	0.9900
13:32304023:C:CC	acceptor_gain	0.9800
13:32304024:T:C	acceptor_gain	0.9800
13:32304025:T:TC	acceptor_gain	0.9800
13:32310728:AAAA:A	acceptor_gain	0.9800
13:32310727:AAAAA:A	acceptor_gain	0.9700
13:32310730:AA:A	acceptor_gain	0.9700
13:32311167:A:C	acceptor_gain	0.9700
13:32315135:T:TA	donor_gain	0.9700
13:32308678:ATGCT:A	donor_loss	0.9600
13:32308680:GCTC:G	donor_loss	0.9600
13:32308681:CT:C	donor_loss	0.9600
13:32308682:T:TC	donor_loss	0.9600
13:32308683:CA:C	donor_loss	0.9600
13:32308684:ACCT:A	donor_loss	0.9600
13:32308685:CCTG:C	donor_loss	0.9600
13:32310728:AAAAC:A	acceptor_loss	0.9600
13:32310729:AAA:A	acceptor_gain	0.9600
13:32310729:AAAC:A	acceptor_loss	0.9600
13:32310730:AACTG:A	acceptor_loss	0.9600
13:32310731:AC:A	acceptor_loss	0.9600
13:32310732:CTGA:C	acceptor_loss	0.9600
13:32310733:T:G	acceptor_loss	0.9600
13:32310635:TTAC:T	donor_loss	0.9500
13:32310637:A:C	donor_loss	0.9500
13:32310638:C:CG	donor_loss	0.9500
13:32310674:TCTCC:T	donor_gain	0.9500

AlphaMissense

2093 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:32310678:C:A	W236C	0.999
13:32310678:C:G	W236C	0.999
13:32310680:A:G	W236R	0.999
13:32310680:A:T	W236R	0.999
13:32310705:G:C	F227L	0.999
13:32310705:G:T	F227L	0.999
13:32310707:A:G	F227L	0.999
13:32308749:T:A	K253N	0.997
13:32308749:T:G	K253N	0.997
13:32308752:G:C	F252L	0.997
13:32308752:G:T	F252L	0.997
13:32308754:A:G	F252L	0.997
13:32310662:A:G	W242R	0.997
13:32310662:A:T	W242R	0.997
13:32310672:A:C	S238R	0.997
13:32310672:A:T	S238R	0.997
13:32310674:T:G	S238R	0.997
13:32303934:C:G	C304S	0.996
13:32303935:A:T	C304S	0.996
13:32308732:C:G	C259S	0.996
13:32308733:A:T	C259S	0.996
13:32310660:C:A	W242C	0.996
13:32310660:C:G	W242C	0.996
13:32310679:C:G	W236S	0.996
13:32310704:G:C	H228D	0.996
13:32308733:A:G	C259R	0.995
13:32308740:A:C	C256W	0.995
13:32308741:C:G	C256S	0.995
13:32308742:A:G	C256R	0.995
13:32308742:A:T	C256S	0.995

dbSNP variants (sampled 300 via entrez): RS1000225205 (13:32312796 T>A), RS1000775109 (13:32311555 TG>T,TGG), RS1001537469 (13:32308015 C>T), RS1001884669 (13:32316048 T>C), RS1002487914 (13:32309851 C>A), RS1002643795 (13:32312829 G>A), RS1002835529 (13:32304359 G>A,C), RS1003152043 (13:32306761 T>C), RS1003381696 (13:32304062 G>T), RS1003568804 (13:32315747 C>G,T), RS1003895035 (13:32308402 A>G,T), RS1003982251 (13:32305266 G>A), RS1004174746 (13:32315955 G>A), RS1004251172 (13:32305426 C>T), RS1004374588 (13:32312435 A>G)

Disease associations

OMIM: gene MIM:620424 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008395_8	End-stage kidney disease	9.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
sodium arsenite	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome