IGF1

insulin like growth factor 1, the group of Neuropeptides

Basic information

Region (hg38): 12:102395873-102481744

Links

ENSG00000017427 ∙ NCBI:3479 ∙ OMIM:147440 ∙ HGNC:5464 ∙ Uniprot:P05019 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• growth delay due to insulin-like growth factor type 1 deficiency (Definitive), mode of inheritance: AR
• growth delay due to insulin-like growth factor type 1 deficiency (Supportive), mode of inheritance: AR
• growth delay due to insulin-like growth factor type 1 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Insulin-like growth factor I deficiency	AR	Audiologic/Otolaryngologic; Endocrine	Recombinant human IGF1 treatment has been reported to improve linear growth and insulin sensitivity; Interventions related to hearing impairment may also be beneficial	Audiologic/Otolaryngologic; Endocrine; Neurologic	8857020; 10323388; 10770174; 14684690; 20668042; 21237682; 22832530

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IGF1 gene.

• Growth delay due to insulin-like growth factor type 1 deficiency (144 variants)
• not provided (43 variants)
• Inborn genetic diseases (5 variants)
• not specified (2 variants)
• IGF1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IGF1 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			2	11		13
missense			23	1	1	25
nonsense			1			1
start loss						0
frameshift	1	1	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			2			2
non coding			94	14	23	131
Total	1	2	121	26	24

Variants in IGF1

This is a list of pathogenic ClinVar variants found in the IGF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-102395885-T-C		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102395909-A-G		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102395924-T-C		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102396014-AGTC-TATTCAATTAGTTACATTTTAG		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jun 14, 2016)
12-102396074-C-G		Growth delay due to insulin-like growth factor type 1 deficiency	Benign (Jan 12, 2018)
12-102396123-G-A		Growth delay due to insulin-like growth factor type 1 deficiency	Benign (Jan 13, 2018)
12-102396196-A-G		Growth delay due to insulin-like growth factor type 1 deficiency	Benign (Jan 12, 2018)
12-102396264-T-A		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102396280-C-G		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102396326-A-G		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 13, 2018)
12-102396388-C-T		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102396414-C-T		Growth delay due to insulin-like growth factor type 1 deficiency	Benign (Jan 12, 2018)
12-102396516-G-A		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 13, 2018)
12-102396577-T-A		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 13, 2018)
12-102396663-T-G		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102396788-C-CT		Growth delay due to insulin-like growth factor type 1 deficiency	Benign (Jun 14, 2016)
12-102396837-G-A		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102396969-G-A		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 13, 2018)
12-102396974-G-A		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102397002-A-T		Growth delay due to insulin-like growth factor type 1 deficiency	Benign (Jan 12, 2018)
12-102397058-C-T		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 13, 2018)
12-102397175-C-A		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 13, 2018)
12-102397175-C-T		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102397218-A-T		Growth delay due to insulin-like growth factor type 1 deficiency	Uncertain significance (Jan 12, 2018)
12-102397237-A-C		Growth delay due to insulin-like growth factor type 1 deficiency	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IGF1	protein_coding	protein_coding	ENST00000307046	4	84779

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.272	0.707	124431	0	6	124437	0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	68	114	0.595	0.00000665	1272
Missense in Polyphen		17	48.293	0.35202		481
Synonymous	-0.581	51	46.0	1.11	0.00000298	373
Loss of Function	1.93	2	7.81	0.256	3.31e-7	105

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000126	0.000126
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000576	0.0000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.00000908	0.00000887
Middle Eastern	0.0000576	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation (PubMed:21076856, PubMed:24132240). Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity). Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiatiating a cascade of down- stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:19578119, PubMed:22351760, PubMed:23696648, PubMed:23243309). {ECO:0000250|UniProtKB:P05017, ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:21076856, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:23243309, ECO:0000269|PubMed:23696648, ECO:0000269|PubMed:24132240}.
• Disease: DISEASE: Insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:608747]: Autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation. {ECO:0000269|PubMed:8857020}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Inflammatory mediator regulation of TRP channels - Homo sapiens (human);Focal adhesion - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Melanoma - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Long-term depression - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Breast cancer - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Glioma - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Aldosterone-regulated sodium reabsorption - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);IGF-Core;MicroRNAs in cardiomyocyte hypertrophy;TarBasePathway;Adipogenesis;Cardiac Progenitor Differentiation;Apoptosis;Polycystic Kidney Disease Pathway;JAK-STAT;Cardiac Hypertrophic Response;Differentiation Pathway;Focal Adhesion;Lung fibrosis;Apoptotic Signaling Pathway;Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Caloric restriction and aging;Endochondral Ossification;Senescence and Autophagy in Cancer;Signal Transduction;regulation of bad phosphorylation;multiple antiapoptotic pathways from igf-1r signaling lead to bad phosphorylation;nfat and hypertrophy of the heart ;skeletal muscle hypertrophy is regulated via akt-mtor pathway;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;igf-1 signaling pathway;IGF signaling;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);GPCR signaling-G alpha s Epac and ERK;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;SHP2 signaling;Hemostasis;the igf-1 receptor and longevity;GPCR signaling-G alpha i;SHC-related events triggered by IGF1R;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;Stabilization and expansion of the E-cadherin adherens junction;IGF1 pathway;Plasma membrane estrogen receptor signaling;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);Ceramide signaling pathway;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.994

Intolerance Scores

• loftool: 0.128
• rvis_EVS: 0.24
• rvis_percentile_EVS: 68.98

Haploinsufficiency Scores

• pHI: 0.664
• hipred: Y
• hipred_score: 0.804
• ghis: 0.469

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.852

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Igf1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; renal/urinary system phenotype; respiratory system phenotype; hematopoietic system 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); reproductive system phenotype; normal 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); neoplasm; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: igf1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: activation of MAPK activity;skeletal system development;cell activation;platelet degranulation;signal transduction;Ras protein signal transduction;muscle organ development;cell population proliferation;positive regulation of cell population proliferation;response to heat;glycolate metabolic process;regulation of gene expression;regulation of signaling receptor activity;positive regulation of glycoprotein biosynthetic process;positive regulation of cardiac muscle hypertrophy;positive regulation of gene expression;negative regulation of gene expression;phosphatidylinositol 3-kinase signaling;positive regulation of phosphatidylinositol 3-kinase signaling;skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration;muscle hypertrophy;myotube cell development;positive regulation of smooth muscle cell migration;proteoglycan biosynthetic process;positive regulation of cell migration;activation of protein kinase B activity;obsolete positive regulation of protein import into nucleus, translocation;negative regulation of smooth muscle cell apoptotic process;bone mineralization involved in bone maturation;regulation of multicellular organism growth;positive regulation of activated T cell proliferation;positive regulation of tyrosine phosphorylation of STAT protein;negative regulation of apoptotic process;positive regulation of DNA binding;positive regulation of MAPK cascade;protein kinase B signaling;positive regulation of insulin-like growth factor receptor signaling pathway;cellular protein metabolic process;myoblast differentiation;positive regulation of osteoblast differentiation;positive regulation of glycogen biosynthetic process;positive regulation of glycolytic process;positive regulation of mitotic nuclear division;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of glucose import;positive regulation of Ras protein signal transduction;insulin-like growth factor receptor signaling pathway;phosphatidylinositol-mediated signaling;positive regulation of fibroblast proliferation;positive regulation of smooth muscle cell proliferation;positive regulation of epithelial cell proliferation;positive regulation of protein secretion;positive regulation of peptidyl-tyrosine phosphorylation;protein stabilization;myoblast proliferation;negative regulation of oocyte development;positive regulation of cell growth involved in cardiac muscle cell development;ERK1 and ERK2 cascade;positive regulation of calcineurin-NFAT signaling cascade;negative regulation of release of cytochrome c from mitochondria;positive regulation of trophectodermal cell proliferation;cellular response to amyloid-beta;positive regulation of vascular smooth muscle cell proliferation;negative regulation of vascular associated smooth muscle cell apoptotic process;positive regulation of transcription regulatory region DNA binding;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: extracellular region;extracellular space;insulin-like growth factor binding protein complex;platelet alpha granule lumen;alphav-beta3 integrin-IGF-1-IGF1R complex;insulin-like growth factor ternary complex;exocytic vesicle
• Molecular function: insulin receptor binding;insulin-like growth factor receptor binding;integrin binding;hormone activity;protein binding;growth factor activity