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 (896 variants)
Stuve-Wiedemann_syndrome (213 variants)
St�ve-Wiedemann_syndrome_1 (186 variants)
Inborn_genetic_diseases (120 variants)
Connective_tissue_disorder (25 variants)
LIFR-related_disorder (21 variants)
not_specified (11 variants)
Congenital_anomaly_of_kidney_and_urinary_tract (4 variants)
Epileptic_encephalopathy (1 variants)
Global_developmental_delay (1 variants)
Abnormal_cerebral_white_matter_morphology (1 variants)
Hypotonia (1 variants)
Hereditary_breast_ovarian_cancer_syndrome (1 variants)
Absent_speech (1 variants)
Developmental_regression (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. These statistics are base on transcript: NM_001127671.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			13 clinvar	354 clinvar	1 clinvar	368
missense		4 clinvar	351 clinvar	16 clinvar	4 clinvar	375
nonsense	28 clinvar	13 clinvar	1 clinvar			42
start loss						0
frameshift	51 clinvar	16 clinvar	1 clinvar			68
splice donor/acceptor (+/-2bp)		36 clinvar				36
Total	79	69	366	370	5

Highest pathogenic variant AF is 0.0000371812

Loading clinvar variants...

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