LIF

LIF interleukin 6 family cytokine, the group of Interleukin 6 type cytokine family|Receptor ligands

Basic information

Region (hg38): 22:30240452-30246759

Links

ENSG00000128342 ∙ NCBI:3976 ∙ OMIM:159540 ∙ HGNC:6596 ∙ Uniprot:P15018 ∙ 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 LIF gene.

• Inborn genetic diseases (6 variants)
• not specified (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIF 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						0
missense			6	1		7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	1	0

Variants in LIF

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

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

Position	Type	Phenotype	Significance	ClinVar
22-30243664-G-A		not specified	Uncertain significance (Dec 02, 2022)
22-30243785-A-G		not specified	Uncertain significance (Nov 21, 2022)
22-30243839-C-T		not specified	Uncertain significance (Jun 09, 2022)
22-30243851-G-A		not specified	Uncertain significance (Nov 06, 2023)
22-30243962-C-G		not specified	Uncertain significance (Jan 17, 2024)
22-30244000-G-A		not specified	Uncertain significance (Mar 11, 2024)
22-30244004-C-T		not specified	Benign/Likely benign (Nov 01, 2022)
22-30244034-T-C		not specified	Uncertain significance (Nov 21, 2022)
22-30244844-G-A		not specified	Uncertain significance (Nov 29, 2023)
22-30244868-G-A		not specified	Uncertain significance (Mar 02, 2023)
22-30244880-G-A		not specified	Uncertain significance (Jun 16, 2023)
22-30246688-A-T		not specified	Uncertain significance (Dec 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIF	protein_coding	protein_coding	ENST00000249075	3	6405

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.524	0.461	125721	0	4	125725	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.398	109	121	0.898	0.00000776	1315
Missense in Polyphen		35	47.037	0.7441		568
Synonymous	-0.694	66	59.2	1.11	0.00000446	424
Loss of Function	1.96	1	6.30	0.159	3.55e-7	68

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000569	0.0000462
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;MicroRNAs in cardiomyocyte hypertrophy;Adipogenesis;ESC Pluripotency Pathways;Interleukin-10 signaling;Interleukin-4 and 13 signaling;TGF-beta Receptor Signaling;Signaling by Interleukins;IL-6-type cytokine receptor ligand interactions;nfat and hypertrophy of the heart ;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Immune System;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;JAK STAT pathway and regulation;LIF signaling;Direct p53 effectors;GPCR signaling-G alpha i;Validated transcriptional targets of AP1 family members Fra1 and Fra2;Interleukin-6 family signaling (Consensus)

Recessive Scores

• pRec: 0.783

Intolerance Scores

• loftool: 0.397
• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.27

Haploinsufficiency Scores

• pHI: 0.249
• hipred: Y
• hipred_score: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lif
• Phenotype: reproductive 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); 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; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye 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); digestive/alimentary phenotype; muscle phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: blood vessel remodeling;immune response;tyrosine phosphorylation of STAT protein;multicellular organism development;embryo implantation;positive regulation of cell population proliferation;negative regulation of cell population proliferation;regulation of signaling receptor activity;cytokine-mediated signaling pathway;stem cell population maintenance;positive regulation of peptidyl-serine phosphorylation;positive regulation of peptidyl-serine phosphorylation of STAT protein;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of MAPK cascade;regulation of cell differentiation;positive regulation of macrophage differentiation;negative regulation of meiotic nuclear division;positive regulation of transcription by RNA polymerase II;decidualization;negative regulation of hormone secretion;lung alveolus development;muscle organ morphogenesis;neuron development;positive regulation of astrocyte differentiation;leukemia inhibitory factor signaling pathway;stem cell differentiation;positive regulation of peptidyl-tyrosine phosphorylation;lung vasculature development;lung lobe morphogenesis;trophoblast giant cell differentiation;spongiotrophoblast differentiation;negative regulation of ERK1 and ERK2 cascade;positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis;regulation of metanephric nephron tubule epithelial cell differentiation;positive regulation of protein localization to nucleus;positive regulation of histone H3-K27 acetylation;regulation of RNA polymerase II regulatory region sequence-specific DNA binding
• Cellular component: extracellular region;extracellular space;cytosol
• Molecular function: signaling receptor binding;cytokine activity;leukemia inhibitory factor receptor binding;protein binding;growth factor activity