LIFR

LIF receptor subunit alpha, the group of MicroRNA protein coding host genes|Fibronectin type III domain containing|CD molecules

Basic information

Region (hg38): 5:38474668-38608354

Links

ENSG00000113594 ∙ NCBI:3977 ∙ OMIM:151443 ∙ HGNC:6597 ∙ Uniprot:P42702 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Stüve-Wiedemann syndrome (Supportive), mode of inheritance: AR
• Stüve-Wiedemann syndrome 1 (Definitive), mode of inheritance: AR
• Stüve-Wiedemann syndrome 1 (Strong), mode of inheritance: AR
• Stüve-Wiedemann syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stuve-Wiedemann syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	4105362; 8728692; 9382147; 9674905; 9674906; 12514358; 14740318; 18546280; 19371797; 20447141
Individuals can have temperature control anomalies and other manifestations of dysautonomia

ClinVar

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

• not provided (75 variants)
• Stuve-Wiedemann syndrome (8 variants)
• Stüve-Wiedemann syndrome 1 (7 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIFR 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	323		325
missense		2	189	6	6	203
nonsense	29	1	1			31
start loss						0
frameshift	50	7	1			58
inframe indel			4			4
splice donor/acceptor (+/-2bp)	1	27				28
splice region			8	59	4	71
non coding			111	183	72	366
Total	80	37	308	512	78

Highest pathogenic variant AF is 0.0000131

Variants in LIFR

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

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

Position	Type	Phenotype	Significance	ClinVar
5-38474954-C-CT		Stuve-Wiedemann syndrome	Likely benign (Jun 14, 2016)
5-38475031-G-A		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475104-T-C		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475112-G-T		Stuve-Wiedemann syndrome	Uncertain significance (Jan 12, 2018)
5-38475200-A-G		Stuve-Wiedemann syndrome	Conflicting classifications of pathogenicity (Apr 01, 2023)
5-38475209-T-C		Stuve-Wiedemann syndrome	Uncertain significance (Jan 12, 2018)
5-38475215-C-G		Stuve-Wiedemann syndrome	Uncertain significance (Jan 12, 2018)
5-38475279-G-A		Stuve-Wiedemann syndrome	Benign (Jan 12, 2018)
5-38475347-G-C		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475369-T-C		Stuve-Wiedemann syndrome	Uncertain significance (Jan 12, 2018)
5-38475405-G-A		Stuve-Wiedemann syndrome	Benign (Jan 13, 2018)
5-38475455-G-C		Stuve-Wiedemann syndrome	Benign (Jan 13, 2018)
5-38475495-C-T		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475553-T-TTAA		Stuve-Wiedemann syndrome	Uncertain significance (Jun 14, 2016)
5-38475609-A-G		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475670-G-T		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475799-T-G		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475802-G-C		Stuve-Wiedemann syndrome	Uncertain significance (Jan 12, 2018)
5-38475827-T-G		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475925-T-C		Stuve-Wiedemann syndrome	Benign (Jan 13, 2018)
5-38475928-A-G		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38475961-A-G		Stuve-Wiedemann syndrome	Benign (Jan 12, 2018)
5-38476053-C-T		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38476174-T-C		Stuve-Wiedemann syndrome	Uncertain significance (Jan 13, 2018)
5-38476239-T-C		Stuve-Wiedemann syndrome	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIFR	protein_coding	protein_coding	ENST00000263409	19	133392

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.49e-13	1.00	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.241	563	579	0.972	0.0000299	7201
Missense in Polyphen		134	166.46	0.80502		2106
Synonymous	-0.214	201	197	1.02	0.0000105	2040
Loss of Function	3.40	31	59.3	0.523	0.00000319	706

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000174	0.000174
Ashkenazi Jewish	0.000800	0.000794
East Asian	0.000327	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000339	0.000325
Middle Eastern	0.000327	0.000326
South Asian	0.000231	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells.
• Disease: DISEASE: Stueve-Wiedemann syndrome (STWS) [MIM:601559]: Severe autosomal recessive condition and belongs to the group of the bent-bone dysplasias. SWS is characterized by bowing of the lower limbs, with internal cortical thickening, wide metaphyses with abnormal trabecular pattern, and camptodactyly. Additional features include feeding and swallowing difficulties, as well as respiratory distress and hyperthermic episodes, which cause death in the first months of life. The rare survivors develop progressive scoliosis, spontaneous fractures, bowing of the lower limbs, with prominent joints and dysautonomia symptoms, including temperature instability, absent corneal and patellar reflexes, and smooth tongue. {ECO:0000269|PubMed:14740318}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving LIFR is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(5;8)(p13;q12) with PLAG1.
• Pathway: Jak-STAT 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;Physiological and Pathological Hypertrophy of the Heart;Adipogenesis;Oncostatin M Signaling Pathway;ESC Pluripotency Pathways;Transcriptional regulation by RUNX1;Gene expression (Transcription);Signaling by Interleukins;IL-6-type cytokine receptor ligand interactions;Generic Transcription Pathway;Cytokine Signaling in Immune system;JAK STAT MolecularVariation 1;RNA Polymerase II Transcription;Oncostatin_M;Immune System;JAK STAT MolecularVariation 2;JAK STAT pathway and regulation;LIF signaling;RUNX1 regulates transcription of genes involved in interleukin signaling;Transcriptional regulation by RUNX1;Interleukin-6 family signaling (Consensus)

Recessive Scores

• pRec: 0.309

Intolerance Scores

• loftool: 0.794
• rvis_EVS: -0.13
• rvis_percentile_EVS: 44.09

Haploinsufficiency Scores

• pHI: 0.715
• hipred: Y
• hipred_score: 0.674
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lifr
• Phenotype: embryo phenotype; liver/biliary system phenotype; hematopoietic system 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); 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); limbs/digits/tail phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: lifrb
• Affected structure: cranial nerve V
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: regulation of cytokine-mediated signaling pathway;cell surface receptor signaling pathway;positive regulation of cell population proliferation;cytokine-mediated signaling pathway;response to cytokine;oncostatin-M-mediated signaling pathway;leukemia inhibitory factor signaling pathway;ciliary neurotrophic factor-mediated signaling pathway
• Cellular component: plasma membrane;integral component of plasma membrane;external side of plasma membrane;receptor complex;extracellular exosome
• Molecular function: cytokine receptor activity;ciliary neurotrophic factor receptor activity;leukemia inhibitory factor receptor activity;oncostatin-M receptor activity;ciliary neurotrophic factor receptor binding;protein binding;growth factor binding;cytokine binding