CLCF1

cardiotrophin like cytokine factor 1, the group of Interleukin 6 type cytokine family

Basic information

Region (hg38): 11:67364167-67374177

Links

ENSG00000175505 ∙ NCBI:23529 ∙ OMIM:607672 ∙ HGNC:17412 ∙ Uniprot:Q9UBD9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Cold-induced sweating syndrome 1 (Supportive), mode of inheritance: AR
• cold-induced sweating syndrome (Supportive), mode of inheritance: AR
• cold-induced sweating syndrome 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Crisponi/Cold-induced sweating syndrome 2	AR	Neurologic	In the neonatal/early childhood period, the condition can be lethal unless advanced care is instituted; Later, it has been described that cold-induced sweating was alleviated by medical treatment (eg, with clonidine, with lasting effects when co-administered with amitriptyline)	Musculoskeletal; Neurologic	16782820; 20400119

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLCF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLCF1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7		7
missense			15	1		16
nonsense						0
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	8	1

Variants in CLCF1

This is a list of pathogenic ClinVar variants found in the CLCF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-67365138-A-G		Cold-induced sweating syndrome 2	Pathogenic (Jun 15, 2010)
11-67365147-GAGCCCCC-G		not specified	Benign (May 20, 2022)
11-67365215-T-C		not specified	Uncertain significance (Jun 07, 2024)
11-67365221-G-A		not specified	Uncertain significance (Oct 05, 2021)
11-67365224-C-A		Cold-induced sweating syndrome 2	Pathogenic (Jun 27, 2006)
11-67365265-G-A		CLCF1-related disorder	Likely benign (May 25, 2019)
11-67365327-G-A		not specified	Uncertain significance (Mar 28, 2024)
11-67365366-C-T		not specified	Uncertain significance (Apr 07, 2022)
11-67365422-C-T		not specified	Uncertain significance (Jun 29, 2022)
11-67365425-C-T		not specified	Uncertain significance (Sep 16, 2021)
11-67365426-G-A		not specified	Uncertain significance (Jan 23, 2024)
11-67365427-C-T			Likely benign (Aug 16, 2018)
11-67365450-G-C		not specified	Uncertain significance (Mar 20, 2024)
11-67365456-G-A		not specified	Uncertain significance (Dec 11, 2023)
11-67365493-G-T		Cold-induced sweating syndrome 2	Pathogenic (Jun 27, 2006)
11-67365521-T-C		not specified	Uncertain significance (May 30, 2024)
11-67365523-G-A			Likely benign (Dec 31, 2019)
11-67365535-C-T			Likely benign (Dec 14, 2018)
11-67365538-C-T			Likely benign (Dec 31, 2019)
11-67365603-C-T		not specified	Uncertain significance (Jul 19, 2022)
11-67367479-C-T			Uncertain significance (Sep 02, 2021)
11-67367480-G-A		Cold-induced sweating syndrome 2	Uncertain significance (Mar 05, 2018)
11-67367500-C-T			Uncertain significance (Jun 08, 2021)
11-67367503-G-C		not specified	Uncertain significance (Apr 08, 2024)
11-67367510-C-G		not specified	Uncertain significance (Jun 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLCF1	protein_coding	protein_coding	ENST00000312438	3	10010

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.948	0.0519	125731	0	4	125735	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	104	141	0.735	0.00000871	1438
Missense in Polyphen		28	48.076	0.58241		526
Synonymous	0.408	54	58.0	0.932	0.00000333	487
Loss of Function	2.83	0	9.32	0.00	4.86e-7	88

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytokine with B-cell stimulating capability. Binds to and activates the ILST/gp130 receptor. {ECO:0000269|PubMed:10448081, ECO:0000269|PubMed:10500198}.
• Pathway: Cytokine-cytokine receptor interaction - Homo sapiens (human);Signaling by Interleukins;IL-6-type cytokine receptor ligand interactions;Cytokine Signaling in Immune system;Immune System;Glycerophospholipid metabolism;Interleukin-6 family signaling (Consensus)

Recessive Scores

• pRec: 0.248

Intolerance Scores

• loftool: 0.367
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.380
• hipred: Y
• hipred_score: 0.667
• ghis: 0.460

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Clcf1
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); growth/size/body region phenotype

Gene ontology

• Biological process: positive regulation of immunoglobulin production;cell surface receptor signaling pathway;JAK-STAT cascade;positive regulation of cell population proliferation;regulation of signaling receptor activity;cytokine-mediated signaling pathway;B cell differentiation;positive regulation of B cell proliferation;positive regulation of tyrosine phosphorylation of STAT protein;negative regulation of neuron apoptotic process;positive regulation of isotype switching to IgE isotypes;positive regulation of astrocyte differentiation
• Cellular component: extracellular region;CRLF-CLCF1 complex;CNTFR-CLCF1 complex
• Molecular function: signaling receptor binding;cytokine activity;ciliary neurotrophic factor receptor binding;protein binding;growth factor activity;protein heterodimerization activity