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Fetal anomalies v7.3 CLCF1 Ida Ertmanska Classified gene: CLCF1 as Amber List (moderate evidence)
Fetal anomalies v7.3 CLCF1 Ida Ertmanska Added comment: Comment on list classification: There are now 3 unrelated individuals reported in literature with biallelic CLCF1 variants and cold-induced sweating syndrome 2, with campodactyly and elbow contractures being a consistent feature in all 3 cases. Hence, this gene can be promoted to Green at the next update.
Fetal anomalies v7.3 CLCF1 Ida Ertmanska Gene: clcf1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v7.2 CLCF1 Ida Ertmanska gene: CLCF1 was added
gene: CLCF1 was added to Fetal anomalies. Sources: Literature
Q2_26_promote_green tags were added to gene: CLCF1.
Mode of inheritance for gene: CLCF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLCF1 were set to 16782820; 20400119; 32512309
Phenotypes for gene: CLCF1 were set to Cold-induced sweating syndrome 2, OMIM:610313; cold-induced sweating syndrome 2, MONDO:0012467; Elbow contracture, HP:0034391; Bilateral camptodactyly, HP:0005617
Review for gene: CLCF1 was set to GREEN
Added comment: PMID: 32512309 Buers et al., 2020
11-year-old boy of European ancestry, homozygous for CLCF1 c.321C>G, p.Tyr107*, with Crisponi Syndrome/cold-induced sweating syndrome 2.

PMID: 20400119 Hahn et al., 2010
Case 1 - female patient, Hungarian (non-consanguineous parents), 25yo - she had bilateral campodactyly (hands and feet), elbow contractures, dysmorphic features, thoracolumbar scoliosis, dry and scaly skin in neonatal period, and oral-facial weakness; from age 10 years she experienced excessive sweating triggered by cold or stressors; neurodevelopment was normal.
Case 2 - sibling of Case 1, 20yo - similarly affected, with profuse sweating in cold temperatures, difficulty sucking and swallowing in infancy, elbow contracture, campodactyly, scoliosis.
Both sibs had CLCF1 variants c.46T>C, p.Cys16Arg and c.676T>C, p.*226Argext*170 (both absent from gnomAD v4.1.1). No sequence variants detected in CRLF1
Case 3 & 4 - identical presentation, but biallelic CRLF1 variants detected.

PMID: 16782820 Rousseau et al., 2006
Australian man examined at age 46 years - he had feeding difficulties in infancy, lifelong issue of profuse sweating in cold temperatures and unable to sweat in hot conditions; also noted to have elbow contractures, campodactyly and syndactyly, thoracolumbar scoliosis and lumbar lordosis, mild sensorimotor peripheral neuropathy; brain MRI and tomography were normal. No family history. He was compound heterozygous for CLCF1 c.590G>T, p.Arg197Leu and c.321C>A, p.Tyr107* (not in gnomAD v4).

Functional evidence:
PMID: 19098279 Zou et al., 2009 - A complete knock-out of CLCF1 in mice is lethal at P1: underdeveloped motor neurons of the face and jaw prevent the pups from suckling - multifocal neuronal hypoplasia phenotype.

This gene is associated with AR Cold-induced sweating syndrome 2, OMIM:610313 in OMIM (accessed 11th May 2026). CLCF1 is not yet associated with a condition in G2P or ClinGen.
Sources: Literature