MDK

protein-coding

midkine

Gene summary

This gene encodes a member of a small family of secreted growth factors that binds heparin and responds to retinoic acid. The encoded protein promotes cell growth, migration, and angiogenesis, in particular during tumorigenesis. This gene has been targeted as a therapeutic for a variety of different disorders. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

Previous symbols:

NEGF2

MANE transcript

NM_002391.6

Inheritance

—

ClinVar variants

U:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr11:46,380,756-46,383,837

External References & Databases

Ensembl (ENSG00000110492)

Transcript & Mutation Effects

hg38 • Region Span ~3.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MDK variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002391.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			18 clinvar			18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	18	0	0	18

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002391.6	RefSeq	NP_002382.1	4	MANE Select
ENST00000395566.9	Ensembl	ENSP00000378933.4	4	MANE Select
NM_001012333.3	RefSeq	NP_001012333.1	4	Standard
NM_001012334.2	RefSeq	NP_001012334.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mdka	Danio rerio	Structure: retina Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

mdka

Danio rerio

Structure: retina

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOTCH-Core
Signal Transduction
Signaling by NOTCH2
Signaling by NOTCH
NOTCH2 Activation and Transmission of Signal to the Nucleus

Biological Process

behavioral fear response
signal transduction
Notch signaling pathway
nervous system development
short-term memory

Molecular Function

growth factor activity
heparin binding

Cellular Component

extracellular region
cytoplasm
cell projection
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000405308
Coding exons: 4
Length: 3070
Individuals with no LoFs: 125139
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125147
p: 0.0000320

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.331	71	79.3	0.895	0.00000380	917
Missense (PolyPhen)		24	28.715	0.8358		352
Synonymous	0.557	28	32.0	0.875	0.00000158	269
Loss of Function	1.81	2	7.25	0.276	3.13e-7	85

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.000055	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Developmentally regulated, secreted growth factor homologous to pleiotrophin (PTN), which has heparin binding activity. Binds anaplastic lymphoma kinase (ALK) which induces ALK activation and subsequent phosphorylation of the insulin receptor substrate (IRS1), followed by the activation of mitogen-activated protein kinase (MAPK) and PI3-kinase, and the induction of cell proliferation. Involved in neointima formation after arterial injury, possibly by mediating leukocyte recruitment. Also involved in early fetal adrenal gland development (By similarity). {ECO:0000250, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:1768439}.;

Intolerance Scores

LoFtool: 0.312
RVIS EVS: 0.06
RVIS percentile EVS: 58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.972

Gene Damage Prediction

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