DLK1

delta like non-canonical Notch ligand 1

Basic information

Region (hg38): 14:100725704-100738224

Links

ENSG00000185559 ∙ NCBI:8788 ∙ OMIM:176290 ∙ HGNC:2907 ∙ Uniprot:P80370 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLK1 gene.

• Inborn genetic diseases (20 variants)
• not provided (17 variants)
• Silver-Russell syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLK1 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				6	3	9
missense			17	4	5	26
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	18	11	8

Variants in DLK1

This is a list of pathogenic ClinVar variants found in the DLK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-100727093-C-G		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
14-100727130-C-T		Inborn genetic diseases	Uncertain significance (Dec 05, 2022)
14-100727133-A-G		Inborn genetic diseases	Uncertain significance (Dec 17, 2021)
14-100727213-C-T		Central precocious puberty	Uncertain significance (Jun 21, 2023)
14-100728427-A-G		DLK1-related disorder	Benign/Likely benign (Feb 01, 2023)
14-100728431-G-C		Silver-Russell syndrome 1	Uncertain significance (Apr 15, 2021)
14-100728440-G-T			Uncertain significance (May 01, 2022)
14-100728445-T-A		Inborn genetic diseases	Uncertain significance (Jan 31, 2023)
14-100728975-C-T		DLK1-related disorder	Likely benign (Apr 16, 2019)
14-100728976-G-A		Inborn genetic diseases	Likely benign (Nov 15, 2021)
14-100728998-A-G		Silver-Russell syndrome 1	Benign (Apr 01, 2023)
14-100729010-G-A		Inborn genetic diseases	Likely benign (Aug 08, 2022)
14-100729017-C-T		DLK1-related disorder	Likely benign (Jul 01, 2023)
14-100729021-C-A		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
14-100729022-A-T			Benign (Dec 31, 2019)
14-100729029-T-G		Inborn genetic diseases	Uncertain significance (May 22, 2023)
14-100729036-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
14-100729048-G-C		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
14-100729052-A-G		Inborn genetic diseases	Uncertain significance (Apr 12, 2023)
14-100729070-G-A		DLK1-related disorder	Likely benign (Nov 28, 2023)
14-100729185-C-T			Likely benign (Apr 01, 2024)
14-100732047-C-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
14-100732060-C-T		Inborn genetic diseases	Uncertain significance (May 28, 2023)
14-100732089-G-A		DLK1-related disorder	Benign (Dec 31, 2019)
14-100732094-C-A		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLK1	protein_coding	protein_coding	ENST00000341267	5	9498

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0346	0.958	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.583	231	257	0.898	0.0000168	2504
Missense in Polyphen		90	109.78	0.81979		1032
Synonymous	0.358	116	121	0.959	0.00000935	769
Loss of Function	2.35	5	14.7	0.340	6.30e-7	163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000531	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a role in neuroendocrine differentiation.
• Pathway: Adipogenesis;Canonical and Non-canonical Notch signaling;EMT transition in Colorectal Cancer;Signal Transduction;Signaling by NOTCH1;Signaling by NOTCH;Notch signaling pathway;FOXA2 and FOXA3 transcription factor networks;Activated NOTCH1 Transmits Signal to the Nucleus (Consensus)

Recessive Scores

• pRec: 0.356

Intolerance Scores

• loftool: 0.122
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.6

Haploinsufficiency Scores

• pHI: 0.891
• hipred: Y
• hipred_score: 0.812
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.742

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dlk1
• Phenotype: immune system phenotype; skeleton phenotype; vision/eye phenotype; 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; 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); reproductive system phenotype; embryo phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: cell differentiation;negative regulation of Notch signaling pathway
• Cellular component: extracellular space;cytoplasm;integral component of membrane
• Molecular function: molecular_function;calcium ion binding