DLK1 Gene (Protein Coding)

Delta Like Non-Canonical Notch Ligand 1

GC14P105592
GIFtS:
45
This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal a... See more...

Aliases for DLK1 Gene

Aliases for DLK1 Gene

  • Delta Like Non-Canonical Notch Ligand 1 2 3 5
  • PG2 2 3 4
  • Protein Delta Homolog 1 3 4
  • Delta1 2 3
  • Pref-1 2 3
  • DLK-1 3 4
  • DLK 3 4
  • FA1 2 3
  • ZOG 2 3
  • Delta-Like 1 Homolog (Drosophila) 2
  • Delta-Like Homolog (Drosophila) 2
  • Preadipocyte Factor 1 3
  • Delta-Like 1 Homolog 3
  • Fetal Antigen 1 3
  • Secredeltin 3
  • PREF1 3
  • DLK1 5

External Ids for DLK1 Gene

Previous GeneCards Identifiers for DLK1 Gene

  • GC14P098584
  • GC14P095008
  • GC14P099183
  • GC14P100263
  • GC14P101193
  • GC14P081373
  • GC14P101197
  • GC14P101211
  • GC14P101793
  • GC14P103537
  • GC14P103771
  • GC14P103961
  • GC14P104336
  • GC14P102086
  • GC14P102320
  • GC14P102490
  • GC14P102665
  • GC14P102838
  • GC14P103010
  • GC14P103209
  • GC14P103378
  • GC14P104663
  • GC14P105067

Summaries for DLK1 Gene

Entrez Gene Summary for DLK1 Gene

  • This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal allele. A single nucleotide variant in this gene is associated with child and adolescent obesity and shows polar overdominance, where heterozygotes carrying an active paternal allele express the phenotype, while mutant homozygotes are normal. [provided by RefSeq, Nov 2015]

GeneCards Summary for DLK1 Gene

DLK1 (Delta Like Non-Canonical Notch Ligand 1) is a Protein Coding gene. Diseases associated with DLK1 include Temple Syndrome and Idiopathic Central Precocious Puberty. Among its related pathways are Embryonic and Induced Pluripotent Stem Cell Differentiation Pathways and Lineage-specific Markers and Signaling by GPCR. Gene Ontology (GO) annotations related to this gene include calcium ion binding. An important paralog of this gene is PEAR1.

UniProtKB/Swiss-Prot Summary for DLK1 Gene

Gene Wiki entry for DLK1 Gene

Additional gene information for DLK1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DLK1 Gene

Genomics for DLK1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for DLK1 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH14J100726 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 254.9 +5.5 5518 10.3 NFIC SIN3A CUX1 KAT7 SPI1 FOXA1 NRF1 ZBTB33 ATF4 ATF2 DLK1 WDR25 HSALNG0103767 HSALNG0103768 NONHSAG015922.2 HSALNG0103770 RTL1
GH14J100724 Enhancer 0.3 Ensembl dbSUPER 250.7 -1.2 -1204 0.2 DLK1 HSALNG0103765 BEGAIN
GH14J100725 Enhancer 0.3 Ensembl 250.7 -0.8 -804 0.2 ZIC2 DLK1 HSALNG0103765 HSALNG0103767 BEGAIN
GH14J100819 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 16.9 +100.8 100831 13.4 ATF2 CEBPA CTCF FOXA2 SMAD4 ZNF511 SAP130 RFX5 TEAD3 JUND MEG3 ENSG00000274884 GQ183494 HSALNG0103778-001 HSALNG0103778-002 DLK1 MIR493 MIR337 MIR431 MIR127
GH14J100658 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 17.6 -61.7 -61696 14.4 IKZF1 ZNF592 ZMYM3 CEBPA NFIC ZIC2 CHD4 CTCF REST BHLHE40 LINC00523 LOC105370667 DLK1 BEGAIN WARS1 WDR25 MEG9 MIR493 MIR127 MIR431
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DLK1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DLK1

Top Transcription factor binding sites by QIAGEN in the DLK1 gene promoter:
  • Evi-1
  • GATA-2
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for DLK1 Gene

Latest Assembly
chr14:100,725,705-100,738,224
(GRCh38/hg38)
Size:
12,520 bases
Orientation:
Plus strand

Previous Assembly
chr14:101,193,229-101,204,561
(GRCh37/hg19 by Entrez Gene)
Size:
11,333 bases
Orientation:
Plus strand

chr14:101,192,042-101,201,539
(GRCh37/hg19 by Ensembl)
Size:
9,498 bases
Orientation:
Plus strand

Genomic View for DLK1 Gene

Genes around DLK1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DLK1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DLK1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for DLK1 Gene

Proteins for DLK1 Gene

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  • Protein details for DLK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P80370-DLK1_HUMAN
    Recommended name:
    Protein delta homolog 1
    Protein Accession:
    P80370
    Secondary Accessions:
    • P15803
    • Q96DW5

    Protein attributes for DLK1 Gene

    Size:
    383 amino acids
    Molecular mass:
    41300 Da
    Quaternary structure:
    • Monomer. Interacts with SH3RF2 (By similarity).
    SequenceCaution:
    • Sequence=CAA35582.1; Type=Frameshift; Evidence={ECO:0000305};

    Alternative splice isoforms for DLK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DLK1 Gene

Protein Expression for DLK1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for DLK1 Gene

  • N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.
  • Glycosylation at Ser94, Asn100, Thr143, Ser163, Asn165, Asn172, Ser214, Thr222, Ser251, Thr256, Ser260, and Thr269
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • DLK1_HUMAN (745)

Other Protein References for DLK1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for DLK1 Gene

Domains & Families for DLK1 Gene

Gene Families for DLK1 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for DLK1 Gene

InterPro:
Blocks:
  • Aspartic acid and asparagine hydroxylation site
  • Laminin-type EGF-like domain
  • Type I EGF

Suggested Antigen Peptide Sequences for DLK1 Gene

GenScript: Design optimal peptide antigens:
  • pG2 (DLK1_HUMAN)
  • Delta-like 1 (Q0H2C6_HUMAN)
  • Brevideltin (Q45KX0_HUMAN)
  • Secredeltin (Q4U3E1_HUMAN)
  • Delta-like 1 homolog (Drosophila) (Q969Y6_HUMAN)
genes like me logo Genes that share domains with DLK1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for DLK1 Gene

Function for DLK1 Gene

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  6. Cell Lines for research

Molecular function for DLK1 Gene

UniProtKB/Swiss-Prot Function:
May have a role in neuroendocrine differentiation.
GENATLAS Biochemistry:
delta (Drosophila)-like 1,member of the EGF-like homeotic family,involved in cell differentiation in a justacrine/paracrine manner and in the pathogenesis of NF1,participating in the control of cell differentiation of several cell type,including small cell lung cancer lines,immune stem cells,B cells and adrenal glumerulose cells

Phenotypes From GWAS Catalog for DLK1 Gene

Gene Ontology (GO) - Molecular Function for DLK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003674 molecular_function ND --
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 32814053
genes like me logo Genes that share ontologies with DLK1: view
genes like me logo Genes that share phenotypes with DLK1: view

Human Phenotype Ontology for DLK1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for DLK1 Gene

MGI Knock Outs for DLK1:

Animal Models for research

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DLK1

Clone products for research

  • Addgene plasmids for DLK1

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for DLK1 Gene

Localization for DLK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DLK1 Gene

Membrane. Single-pass type I membrane protein. Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DLK1 gene
Compartment Confidence
extracellular 5
plasma membrane 3
cytoskeleton 3
nucleus 3
cytosol 3
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DLK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IDA 7925474
GO:0005737 cytoplasm IEA --
GO:0016020 membrane IBA 21873635
GO:0016021 integral component of membrane TAS,IEA --
genes like me logo Genes that share ontologies with DLK1: view

Pathways & Interactions for DLK1 Gene

genes like me logo Genes that share pathways with DLK1: view

SIGNOR curated interactions for DLK1 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for DLK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0030154 cell differentiation IEA --
GO:0045746 negative regulation of Notch signaling pathway IDA 25093684
genes like me logo Genes that share ontologies with DLK1: view

Drugs & Compounds for DLK1 Gene

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  1. Drug products for research

(4) Drugs for DLK1 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for DLK1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with DLK1: view

Transcripts for DLK1 Gene

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mRNA/cDNA for DLK1 Gene

3 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for DLK1

Clone products for research

  • Addgene plasmids for DLK1

Alternative Splicing Database (ASD) splice patterns (SP) for DLK1 Gene

No ASD Table

Relevant External Links for DLK1 Gene

GeneLoc Exon Structure for
DLK1

Expression for DLK1 Gene

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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DLK1 Gene

mRNA expression in normal human tissues for DLK1 Gene
mRNA expression by GTEx for DLK1 GenemRNA expression by BioGPS for DLK1 Gene

mRNA differential expression in normal tissues according to GTEx for DLK1 Gene

This gene is overexpressed in Adrenal Gland (x27.7), Pituitary (x17.2), and Ovary (x4.8).

Protein differential expression in normal tissues from HIPED for DLK1 Gene

This gene is overexpressed in Fetal Brain (24.4), Urine (22.5), and Fetal ovary (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for DLK1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DLK1

SOURCE GeneReport for Unigene cluster for DLK1 Gene:

Hs.533717

mRNA Expression by UniProt/SwissProt for DLK1 Gene:

P80370-DLK1_HUMAN
Tissue specificity: Found within the stromal cells in close contact to the vascular structure of placental villi, yolk sac, fetal liver, adrenal cortex and pancreas and in the beta cells of the islets of Langerhans in the adult pancreas. Found also in some forms of neuroendocrine lung tumor tissue.

Evidence on tissue expression from TISSUES for DLK1 Gene

  • Adrenal gland(4.7)
  • Pancreas(4.5)
  • Nervous system(3.4)
  • Liver(3.2)
  • Muscle(2.9)
  • Heart(2.7)
  • Lung(2.2)
  • Skin(2)
genes like me logo Genes that share expression patterns with DLK1: view

Primer products for research

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for DLK1 Gene

Orthologs for DLK1 Gene

This gene was present in the common ancestor of animals.

Orthologs for DLK1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia DLK1 29 30
  • 99.22 (n)
 OneToOne
Dog
(Canis familiaris)
 Mammalia DLK1 29 30
  • 90.1 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Dlk1 29 16 30
  • 87.03 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Dlk1 29
  • 87.03 (n)
Cow
(Bos Taurus)
 Mammalia DLK 30
  • 83 (a)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia DLK1 30
  • 57 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia DLK1 30
  • 50 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves DLK1 29 30
  • 58.57 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia DLK1 30
  • 50 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia dlk1 29
  • 54.85 (n)
Zebrafish
(Danio rerio)
 Actinopterygii LOC101883341 29
  • 55.9 (n)
Fruit Fly
(Drosophila melanogaster)
 Insecta wry 30
  • 7 (a)
 OneToMany
Species where no ortholog for DLK1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for DLK1 Gene

ENSEMBL:
Gene Tree for DLK1 (if available)
TreeFam:
Gene Tree for DLK1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DLK1: view image
Alliance of Genome Resources:
Additional Orthologs for DLK1

Paralogs for DLK1 Gene

Paralogs for DLK1 Gene

(13) SIMAP similar genes for DLK1 Gene using alignment to 7 proteins:

  • DLK1_HUMAN
  • G3V2R7_HUMAN
  • G3XAH5_HUMAN
  • Q0H2C6_HUMAN
  • Q45KX0_HUMAN
  • Q4U3E1_HUMAN
  • Q969Y6_HUMAN
genes like me logo Genes that share paralogs with DLK1: view

Variants for DLK1 Gene

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Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DLK1 Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
rs115349979 Benign: not provided 100,734,882(+) G/C
NM_003836.6(DLK1):c.1138G>C (p.Asp380His) 		MISSENSE
rs116078181 Benign: not provided 100,734,177(+) G/T
NM_003836.6(DLK1):c.433G>T (p.Val145Leu) 		MISSENSE
rs13329039 Benign: not provided 100,728,427(+) A/G
NM_003836.6(DLK1):c.99A>G (p.Gln33=) 		SYNONYMOUS
rs139584149 Benign: not provided 100,734,869(+) C/T
NM_003836.6(DLK1):c.1125C>T (p.Ser375=) 		SYNONYMOUS
rs143814604 Likely Benign: not provided 100,734,281(+) C/T
NM_003836.6(DLK1):c.537C>T (p.Cys179=) 		SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for DLK1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for DLK1 Gene

Variant ID Type Subtype PubMed ID
esv2751158 CNV gain 17911159
esv3635516 CNV gain 21293372
nsv1425 CNV insertion 18451855
nsv456428 CNV loss 19166990
nsv470668 CNV loss 18288195
nsv483116 CNV gain 15286789
nsv521690 CNV loss 19592680
nsv525723 CNV loss 19592680
nsv565787 CNV loss 21841781
nsv565858 CNV loss 21841781
nsv832876 CNV loss 17160897

Variation tolerance for DLK1 Gene

Residual Variation Intolerance Score: 25.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.97; 68.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DLK1 Gene

Human Gene Mutation Database (HGMD)
DLK1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DLK1
Leiden Open Variation Database (LOVD)
DLK1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DLK1 Gene

Disorders for DLK1 Gene

MalaCards: The human disease database

(22) MalaCards diseases for DLK1 Gene - From: ORP, COP, and GCD

Disorder Aliases PubMed IDs
temple syndrome
  • uniparental disomy, maternal, chromosome 14
idiopathic central precocious puberty
kagami-ogata syndrome
  • uniparental disomy, paternal, chromosome 14
maternal uniparental disomy
uniparental disomy of chromosome 14
  • upd(14)
- elite association - COSMIC cancer census association via MalaCards
Search DLK1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DLK1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with DLK1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DLK1 Gene

Publications for DLK1 Gene

  1. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2. (PMID: 7925474) Jensen CH … Teisner B (European journal of biochemistry 1994) 2 3 4 22
  2. dlk, pG2 and Pref-1 mRNAs encode similar proteins belonging to the EGF-like superfamily. Identification of polymorphic variants of this RNA. (PMID: 7711066) Lee YL … Laborda J (Biochimica et biophysica acta 1995) 3 4 22
  3. Studies on the isolation, structural analysis and tissue localization of fetal antigen 1 and its relation to a human adrenal-specific cDNA, pG2. (PMID: 8501199) Jensen CH … Skjødt K (Human reproduction (Oxford, England) 1993) 3 4 22
  4. dlk, a putative mammalian homeotic gene differentially expressed in small cell lung carcinoma and neuroendocrine tumor cell line. (PMID: 8095043) Laborda J … Notario V (The Journal of biological chemistry 1993) 2 3 4
  5. Paternally Inherited DLK1 Deletion Associated With Familial Central Precocious Puberty. (PMID: 28324015) Dauber A … Latronico AC (The Journal of clinical endocrinology and metabolism 2017) 3 72

ExternalLinks

View latest publications for DLK1 gene in Mastermind

Products for DLK1 Gene

  • Addgene plasmids for DLK1

Sources for DLK1 Gene