LIFR

Chr 5AR

LIF receptor subunit alpha

NCBI Gene: 3977ENSG00000113594UniProt: P42702

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

Primary Disease Associations & Inheritance

Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndromeMIM #601559
AR
1422
ClinVar variants
59
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LIFR
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 211 VUS of 1422 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.71LOEUF
pLI 0.000
Z-score 3.40
OE 0.52 (0.39–0.71)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.24Z-score
OE missense 0.97 (0.91–1.04)
563 obs / 579.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.39–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.91–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 31 / 59.3Missense obs/exp: 563 / 579.3Syn Z: -0.21

ClinVar Variant Classifications

1422 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic30
VUS211
Likely Benign220
Benign5
Conflicting5
29
Pathogenic
30
Likely Pathogenic
211
VUS
220
Likely Benign
5
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
12
0
29
Likely Pathogenic
23
1
6
0
30
VUS
0
194
12
5
211
Likely Benign
0
2
124
94
220
Benign
0
0
5
0
5
Conflicting
—5
Total4019715999500

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LIFR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LIFR-related Stuve-Wiedeman syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndrome

MIM #601559

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
HMGA2-WIF1 Rearrangements Characterize a Distinctive Subset of Salivary Pleomorphic Adenomas With Prominent Trabecular (Canalicular Adenoma-like) Morphology.
Agaimy A et al.·Am J Surg Pathol
2022
Super-Enhancer Driven LIF/LIFR-STAT3-SOX2 Regulatory Feedback Loop Promotes Cancer Stemness in Head and Neck Squamous Cell Carcinoma.
Li J et al.·Adv Sci (Weinh)
2024
Stüve-Wiedemann syndrome: LIFR and associated cytokines in clinical course and etiology.
Mikelonis D et al.·Orphanet J Rare Dis
2014Review
The Pleiotropic role, functions and targeted therapies of LIF/LIFR axis in cancer: Old spectacles with new insights.
Halder S et al.·Biochim Biophys Acta Rev Cancer
2022Review
Leukemia inhibitory factor (LIF) receptor amplifies pathogenic activation of fibroblasts in lung fibrosis.
Nguyen HN et al.·Proc Natl Acad Sci U S A
2024
Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF.
Michaëlsson E et al.·JACC Heart Fail
2023
HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer.
Clements ME et al.·Oncogene
2021
LncRNA LIFR-AS1 overexpression suppressed the progression of serous ovarian carcinoma.
Liu F et al.·J Clin Lab Anal
2022
Association between circulating inflammatory proteins and benign prostatic disease: a Mendelian randomization study.
Cao H et al.·Sci Rep
2024
Expanding the Molecular Spectrum of Carcinoma Ex Pleomorphic Adenoma: An Analysis of 84 Cases With a Novel HMGA2::LINC02389 Fusion.
de Lima-Souza RA et al.·Am J Surg Pathol
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Tissue IL-6/LIF/LIFR and CXCL9 Expression Correlates with High-Risk NBI Patterns and Squamous Cell Carcinoma in Vocal Fold Lesions.
Barańska M et al.·Int J Mol Sci
2026
Artificial Intelligence Driven Virtual Screening and Molecular Docking Approaches Identified LIFR, BTG2, EPHX2, and PAK3 as Targets and BI-2536, AP-24534, and AZ-628 as Repurposed Drugs for PDAC.
Pragya et al.·IEEE Trans Comput Biol Bioinform
2026
p16Ink4a-Positive Hepatocytes Drive Liver Fibrosis Through Activation of LIFR Family Pathway.
Nishikawa K et al.·Adv Sci (Weinh)
2026
LIFR antagonism reverses epithelial pro-CAF programs in pancreatic ductal adenocarcinoma.
Giorgio CD et al.·Biochem Pharmacol
2026
From chronic gastritis to gastric cancer: Mendelian randomisation and multi-omics interrogation of leukaemia inhibitory factor receptor (LIFR), hepatocyte growth factor (HGF), serine protease inhibitor E1 (SERPINE1) and interleukin-10 receptor subunit beta (IL10RB).
Lu L et al.·Int J Biol Macromol
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools