CRLF1

cytokine receptor like factor 1, the group of Fibronectin type III domain containing

Basic information

Region (hg38): 19:18572220-18607741

Links

ENSG00000006016

∙ NCBI:9244 ∙ OMIM:604237 ∙ HGNC:2364 ∙ Uniprot:O75462 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Cold-induced sweating syndrome 1 (Definitive), mode of inheritance: AR
idiopathic achalasia (Supportive), mode of inheritance: AR
Cold-induced sweating syndrome 1 (Supportive), mode of inheritance: AR
cold-induced sweating syndrome (Supportive), mode of inheritance: AR
Cold-induced sweating syndrome 1 (Strong), mode of inheritance: AR
Cold-induced sweating syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Crisponi/Cold-induced sweating syndrome, type 1	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)	Musculoskeletal; Neurologic	8723066; 12509788; 17436252; 17436251; 18837055; 19012339; 20186812; 20400119; 21326283; 21370513; 23026229

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRLF1 gene.

not_provided (105 variants)
Inborn_genetic_diseases (58 variants)
Cold-induced_sweating_syndrome_1 (29 variants)
not_specified (12 variants)
Cold-induced_sweating_syndrome (4 variants)
CRLF1-related_disorder (3 variants)
Cone-rod_dystrophy_12 (1 variants)
Crisponi/Cold-induced_sweating_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRLF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004750.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	44 clinvar	3 clinvar	48
missense	2 clinvar	3 clinvar	81 clinvar	4 clinvar	1 clinvar	91
nonsense	6 clinvar					6
start loss		2				2
frameshift	11 clinvar	4 clinvar	1 clinvar			16
splice donor/acceptor (+/-2bp)		3 clinvar				3
Total	19	12	83	48	4

Highest pathogenic variant AF is 0.00003534958

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRLF1	protein_coding	protein_coding	ENST00000392386	9	35522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000400	0.959	125690	0	54	125744	0.000215

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.475	224	245	0.915	0.0000150	2656
Missense in Polyphen		92	96.912	0.94931		1035
Synonymous	0.193	109	112	0.977	0.00000725	908
Loss of Function	1.86	10	18.7	0.535	8.10e-7	213

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000773	0.000773
Ashkenazi Jewish	0.000499	0.000496
East Asian	0.000275	0.000272
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000136	0.000132
Middle Eastern	0.000275	0.000272
South Asian	0.000132	0.000131
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Cytokine receptor subunit, possibly playing a regulatory role in the immune system and during fetal development. May be involved in nervous system development.;
Disease: DISEASE: Crisponi/Cold-induced sweating syndrome 1 (CISS1) [MIM:272430]: An autosomal recessive disorder characterized by profuse sweating induced by cool surroundings (temperatures of 7 to 18 degrees Celsius). Patients manifest, in the neonatal period, orofacial weakness with impaired sucking and swallowing, resulting in poor feeding. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. These features are referred to as Crisponi syndrome and can result in early death in infancy. Patients who survive into childhood have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Additional abnormalities include a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend the elbows and kyphoscoliosis. {ECO:0000269|PubMed:12509788, ECO:0000269|PubMed:16952376, ECO:0000269|PubMed:17436251, ECO:0000269|PubMed:17436252, ECO:0000269|PubMed:21326283, ECO:0000269|PubMed:23026229, ECO:0000269|PubMed:24488861}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: JAK-STAT-Core;Signaling by Interleukins;IL-6-type cytokine receptor ligand interactions;Cytokine Signaling in Immune system;Immune System;Interleukin-6 family signaling (Consensus)

Recessive Scores

pRec: 0.198

Intolerance Scores

loftool: 0.328
rvis_EVS: -0.65
rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

pHI: 0.447
hipred: N
hipred_score: 0.485
ghis: 0.604

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.982

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Crlf1
Phenotype: 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); 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: ureteric bud development;positive regulation of cell population proliferation;regulation of signaling receptor activity;cytokine-mediated signaling pathway;positive regulation of tyrosine phosphorylation of STAT protein;negative regulation of neuron apoptotic process;interleukin-27-mediated signaling pathway;negative regulation of motor neuron apoptotic process
Cellular component: extracellular region;extracellular space;cytosol;external side of plasma membrane;receptor complex;CRLF-CLCF1 complex
Molecular function: cytokine receptor activity;cytokine activity;ciliary neurotrophic factor receptor binding;protein binding;cytokine binding;protein heterodimerization activity