CRLF1

Chr 19

cytokine receptor like factor 1

Also known as: CISS, CISS1, CLF, CLF-1, NR6, zcytor5

NCBI Gene: 9244ENSG00000006016UniProt: O75462

This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCrisponi/Cold-induced sweating syndrome 1

Clinical highlights

Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
20
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.91
LOEUF
LOF
Mechanism· G2P
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GeneReview available — CRLF1
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.91LOEUF
pLI 0.000
Z-score 1.86
OE 0.54 (0.33–0.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.47Z-score
OE missense 0.91 (0.82–1.02)
224 obs / 244.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.54 (0.33–0.91)
0≤0.351.4
Missense OE?0.91 (0.82–1.02)
0≤0.61.4
Synonymous OE?0.98
0≤1.21.6
LoF obs/exp: 10 / 18.7Missense obs/exp: 224 / 244.9Syn Z: 0.19

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CRLF1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients