CRLF1

Chr 19p12

cytokine receptor like factor 1

Aliases:: CLF-1, CLF, CISS, CISS1
MANE:: ENST00000392386.8

OMIM: 604237 ↗NCBI: 9244 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

CRLF1 · O75462

v62025-08-01

Predicted Aligned Error matrix for CRLF1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

80.3/ 100

Confident

422 residues

Confidence breakdown

Very high(≥ 90)56%
Confident(70–90)19%
Low(50–70)8%
Very low(< 50)18%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Arthrogryposis
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Cold-induced sweating syndrome 1
0.81
cold-induced sweating syndrome
0.64
Crisponi syndrome
0.56
spinal stenosis
0.42
hereditary disease
0.42
dentures
0.29
cone-rod dystrophy 12
0.27
esophageal disorder
0.26
diaphragmatic hernia
0.22
cholelithiasis
0.15

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Cytokine receptor-like factor 1

Functions as secretory protein carrier chaperone that promotes cellular release (PubMed:10966616). Also functions as a cytokine subunit within the CRLF1-CLCF1 heterodimer, which engages the CNTF receptor complex (CNTFR, IL6ST/gp130, LIFR) (PubMed:10966616). As part of the CRLF-CLCF1 complex, binds to CNTFR, induces dimerization of the IL6ST/gp130 and LIFR, which activates JAK tyrosine kinases (JAK1 or JAK2 and to lesser extent TYK2) bound to their intracellular domains (PubMed:11294841). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STAT3 and to lesser extent STAT1) (PubMed:10966616, PubMed:11294841). Moreover, CLCF1/CLF heterodimer induces tyrosine phosphorylation of PTPN11, that associates with IL6ST/gp130-LIFR, which in turn recruits PIK3 protein kinase followed by AKT protein phosphorylation (PubMed:11294841). Participates in the survival of embryonic motor neurons (PubMed:10966616). May also play a regulatory role in the immune system (PubMed:9686600)