CLCF1

Summary

CLCF1 (cardiotrophin like cytokine factor 1, HGNC:17412) is a protein-coding gene on chromosome 11q13.2, encoding Cardiotrophin-like cytokine factor 1 (Q9UBD9). In complex with CRLF1, forms a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development.

This gene is a member of the glycoprotein (gp)130 cytokine family and encodes cardiotrophin-like cytokine factor 1 (CLCF1). CLCF1 forms a heterodimer complex with cytokine receptor-like factor 1 (CRLF1). This dimer competes with ciliary neurotrophic factor (CNTF) for binding to the ciliary neurotrophic factor receptor (CNTFR) complex, and activates the Jak-STAT signaling cascade. CLCF1 can be actively secreted from cells by forming a complex with soluble type I CRLF1 or soluble CNTFR. CLCF1 is a potent neurotrophic factor, B-cell stimulatory agent and neuroendocrine modulator of pituitary corticotroph function. Defects in CLCF1 cause cold-induced sweating syndrome 2 (CISS2). This syndrome is characterized by a profuse sweating after exposure to cold as well as congenital physical abnormalities of the head and spine. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 23529 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cold-induced sweating syndrome 2 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 69 total — 4 pathogenic
• Phenotypes (HPO): 34
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_013246

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17412
Approved symbol	CLCF1
Name	cardiotrophin like cytokine factor 1
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	NNT1, BSF3, CLC, NR6, CISS2, BSF-3, NNT-1
Ensembl gene	ENSG00000175505
Ensembl biotype	protein_coding
OMIM	607672
Entrez	23529

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000312438, ENST00000533438

RefSeq mRNA: 2 — MANE Select: NM_013246 NM_001166212, NM_013246

CCDS: CCDS31617, CCDS53666

Canonical transcript exons

ENST00000312438 — 3 exons

Exon	Start	End
ENSE00001213782	67373524	67373598
ENSE00001337542	67364168	67365630
ENSE00003560147	67367460	67367626

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 89.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0714 / max 569.5814, expressed in 1429 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120905	10.5751	1222
120906	1.9125	816
120908	0.3571	156
120907	0.2092	99
120904	0.0175	2

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	89.66	gold quality
metanephros cortex	UBERON:0010533	88.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.53	gold quality
body of uterus	UBERON:0009853	85.09	gold quality
gall bladder	UBERON:0002110	84.49	gold quality
cartilage tissue	UBERON:0002418	84.05	gold quality
mucosa of stomach	UBERON:0001199	82.99	gold quality
granulocyte	CL:0000094	82.80	gold quality
endocervix	UBERON:0000458	82.49	gold quality
right uterine tube	UBERON:0001302	82.20	gold quality
stromal cell of endometrium	CL:0002255	81.94	gold quality
omental fat pad	UBERON:0010414	81.91	gold quality
peritoneum	UBERON:0002358	81.87	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.68	gold quality
lower esophagus	UBERON:0013473	81.62	gold quality
ascending aorta	UBERON:0001496	81.50	gold quality
thoracic aorta	UBERON:0001515	81.47	gold quality
descending thoracic aorta	UBERON:0002345	81.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.91	gold quality
nerve	UBERON:0001021	80.79	gold quality
tibial nerve	UBERON:0001323	80.79	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	80.68	gold quality
right lobe of thyroid gland	UBERON:0001119	80.58	gold quality
left lobe of thyroid gland	UBERON:0001120	80.11	gold quality
aorta	UBERON:0000947	80.00	gold quality
minor salivary gland	UBERON:0001830	79.65	gold quality
body of stomach	UBERON:0001161	79.25	gold quality
thyroid gland	UBERON:0002046	79.21	gold quality
tongue squamous epithelium	UBERON:0006919	79.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting CLCF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3150A-3P	99.76	64.44	1640

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• activation of the Jak-STAT cascade is essential for corticotroph NNT-1/BSF-3 signaling. (PMID:12639901)
• Structural and docking interaction studies showed that the R197L substitution destabilized the contact site between CLC and CNTFRalpha. (PMID:16782820)
• Ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin share a conserved binding site on the ciliary neurotrophic factor receptor alpha chain (PMID:18728012)
• albuminuria in focal segmental glomerulosclerosis is related to qualitative or quantitative changes in the CLCF1-CRLF1 complex. (PMID:25843671)
• Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and their roles in development, adulthood, cancer and degenerative disorders. (PMID:26198769)
• CLF-1, based on its binding site for CLC and on two additional and independent sites for CNTFRalpha and sorLA, is a key player in CLC and CNTFRalpha signaling and turnover. (PMID:26858303)
• Very low-density lipoproteins (VLDL)- and LDL-CLCF1 binding was confirmed using proximity and ligand blots assays. CLCF1-induced STAT3 phosphorylation was significantly reduced when the cytokine was complexed with VLDL. (PMID:29507344)
• Crisponi/cold-induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts. (PMID:31497877)
• we nominate blockade of CLCF1-CNTFR signaling as a novel therapeutic opportunity for lung adenocarcinoma and potentially for other tumor types in which CLCF1 is present in the tumor microenvironment. (PMID:31700175)
• Association of cardiotrophin-like cytokine factor 1 levels in peripheral blood mononuclear cells with bone mineral density and osteoporosis in postmenopausal women. (PMID:33430863)
• Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-kappaB signaling pathway. (PMID:34364014)
• CRLF1 and CLCF1 in Development, Health and Disease. (PMID:35055176)
• CLCF1 Is a Novel Potential Immune-Related Target With Predictive Value for Prognosis and Immunotherapy Response in Glioma. (PMID:35265072)
• Intrahepatic paracrine signaling by cardiotrophin-like cytokine factor 1 ameliorates diet-induced NASH in mice. (PMID:35950514)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	clcf1	ENSDARG00000076140
mus_musculus	Clcf1	ENSMUSG00000040663
rattus_norvegicus	Clcf1	ENSRNOG00000018752

Paralogs (1): CTF1 (ENSG00000150281)

Protein

Protein identifiers

Cardiotrophin-like cytokine factor 1 — Q9UBD9 (reviewed: Q9UBD9)

Alternative names: B-cell-stimulating factor 3, Novel neurotrophin-1

All UniProt accessions (1): Q9UBD9

UniProt curated annotations — full annotation on UniProt →

Function. In complex with CRLF1, forms a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development. Also stimulates B-cells. Binds to and activates the ILST/gp130 receptor.

Subunit / interactions. Forms a heteromeric complex with cardiotrophin-like cytokine CRLF1/CLF-1; the CRLF1-CLCF1 complex is a ligand for the ciliary neurotrophic factor receptor/CNTFR. The CRLF1-CLCF1 heterodimer binds SORL1 (via N-terminal ectodomain); within this complex, the interaction is mediated predominantly by the CRLF1 moiety. The tripartite signaling complex formed by CRLF1, CLCF1 and CNTFR also binds SORL1.

Subcellular location. Secreted.

Tissue specificity. Expressed predominantly in lymph nodes, spleen, peripheral blood lymphocytes, bone marrow, and fetal liver.

Disease relevance. Crisponi/Cold-induced sweating syndrome 2 (CISS2) [MIM:610313] 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the IL-6 superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBD9-1	1	yes
Q9UBD9-2	2

RefSeq proteins (2): NP_001159684, NP_037378* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR010681	PRF/CT	Family

Pfam: PF06875

UniProt features (16 total): helix 7, strand 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8D7H	ELECTRON MICROSCOPY	3.4
8D7R	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBD9-F1	82.59	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 29

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions

MSigDB gene sets: 516 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, FXR_IR1_Q6, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MYOGENIN_Q6, GOBP_TOLERANCE_INDUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GCANCTGNY_MYOD_Q6

GO Biological Process (11): positive regulation of immunoglobulin production (GO:0002639), cell surface receptor signaling pathway (GO:0007166), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of cell population proliferation (GO:0008284), cytokine-mediated signaling pathway (GO:0019221), B cell differentiation (GO:0030183), positive regulation of B cell proliferation (GO:0030890), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of isotype switching to IgE isotypes (GO:0048295), positive regulation of astrocyte differentiation (GO:0048711), cell surface receptor signaling pathway via STAT (GO:0097696)

GO Molecular Function (6): signaling receptor binding (GO:0005102), cytokine activity (GO:0005125), ciliary neurotrophic factor receptor binding (GO:0005127), growth factor activity (GO:0008083), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), CRLF-CLCF1 complex (GO:0097058), CNTFR-CLCF1 complex (GO:0097059)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-6 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
cell surface receptor signaling pathway	2
receptor ligand activity	2
extracellular protein-containing complex	2
immunoglobulin production	1
regulation of immunoglobulin production	1
positive regulation of production of molecular mediator of immune response	1
cell surface receptor signaling pathway via STAT	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular response to cytokine stimulus	1
lymphocyte differentiation	1
B cell activation	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
positive regulation of isotype switching	1
isotype switching to IgE isotypes	1
regulation of isotype switching to IgE isotypes	1
positive regulation of glial cell differentiation	1
astrocyte differentiation	1
regulation of astrocyte differentiation	1
protein binding	1
cytokine receptor binding	1
binding	1
signaling receptor binding	1
signaling receptor activator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLCF1	CRLF1	O75462	997
CLCF1	CNTFR	P26992	881
CLCF1	CNTF	P26441	879
CLCF1	CTF1	Q16619	841
CLCF1	LIFR	P42702	831
CLCF1	IL6ST	P40189	611
CLCF1	OSM	P13725	595
CLCF1	REX1BD	Q96EN9	582
CLCF1	IL11	P20809	581
CLCF1	LIF	P15018	531
CLCF1	OSMR	Q99650	484
CLCF1	IL6	P05231	446
CLCF1	IL31	Q6EBC2	432
CLCF1	IL1A	P01583	402
CLCF1	VCP	P55072	390

IntAct

15 interactions, top by confidence:

A	B	Type	Score
CLCF1	CRLF1	psi-mi:“MI:0915”(physical association)	0.770
CRLF1	CLCF1	psi-mi:“MI:0407”(direct interaction)	0.770
CRLF1	CNTFR	psi-mi:“MI:0915”(physical association)	0.610
APOE	CLCF1	psi-mi:“MI:0915”(physical association)	0.520
CLCF1	CNTFR	psi-mi:“MI:0915”(physical association)	0.490
CRLF1	Cntfr	psi-mi:“MI:0915”(physical association)	0.400
ESR2		psi-mi:“MI:0914”(association)	0.350
PROK1	IDE	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): CLCF1 (Affinity Capture-MS), CLCF1 (Affinity Capture-MS), CLCF1 (Affinity Capture-MS), CLCF1 (Affinity Capture-Western), CLCF1 (Co-purification), CLCF1 (Affinity Capture-RNA), CLCF1 (Affinity Capture-MS), CLCF1 (Affinity Capture-Western), S100A1 (Reconstituted Complex), S100A6 (Reconstituted Complex), S100P (Reconstituted Complex), CLCF1 (Affinity Capture-MS), CLCF1 (Affinity Capture-MS), CLCF1 (Affinity Capture-MS), CLCF1 (Affinity Capture-MS)

ESM2 similar proteins: D3YZZ2, E7ERA6, F2Z333, H3BV60, O00292, O18796, O43508, O43612, O54907, O55232, O55241, O60391, O75462, O75610, O77668, O95633, O95685, P13224, P41155, P56717, Q02833, Q06643, Q14626, Q1LZB9, Q2TBM7, Q4V892, Q5RF19, Q5TM22, Q6IA17, Q6UXT9, Q6ZMM2, Q862Z7, Q86VR8, Q86YD3, Q8BQB4, Q8NBV8, Q8TAD2, Q99640, Q99MF4, Q9BZR6

Diamond homologs: Q9QZM3, Q9UBD9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CLCF1	up-regulates	IL6ST	binding
CLCF1	up-regulates	CNTFR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

69 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	41
Likely benign	14
Benign	4

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
21503	NM_013246.3(CLCF1):c.46T>C (p.Cys16Arg)	Pathogenic
2930	NM_013246.3(CLCF1):c.321C>A (p.Tyr107Ter)	Pathogenic
2931	NM_013246.3(CLCF1):c.590G>T (p.Arg197Leu)	Pathogenic
39568	NM_013246.3(CLCF1):c.676T>C (p.Ter226Arg)	Pathogenic

SpliceAI

1562 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67367458:A:AC	donor_gain	1.0000
11:67367459:C:CC	donor_gain	1.0000
19:39731505:CCTAC:C	acceptor_loss	1.0000
19:39731506:C:CA	acceptor_loss	1.0000
19:39734293:T:C	donor_gain	1.0000
19:39737936:A:AC	donor_gain	1.0000
19:39737937:C:CC	donor_gain	1.0000
11:67367451:GATAC:G	donor_loss	0.9900
11:67367452:ATACT:A	donor_loss	0.9900
11:67367453:TAC:T	donor_loss	0.9900
11:67367454:ACT:A	donor_loss	0.9900
11:67367456:TCAC:T	donor_loss	0.9900
11:67367456:TCACA:T	donor_loss	0.9900
11:67367457:C:CC	donor_loss	0.9900
11:67367458:A:C	donor_loss	0.9900
11:67367458:AC:A	donor_loss	0.9900
11:67367459:C:CT	donor_loss	0.9900
11:67368290:A:AC	donor_gain	0.9900
11:67368291:C:CC	donor_gain	0.9900
11:67373518:TCCTA:T	donor_loss	0.9900
11:67373519:CCTA:C	donor_loss	0.9900
11:67373520:CTA:C	donor_loss	0.9900
11:67373520:CTACC:C	donor_loss	0.9900
11:67373521:TACC:T	donor_loss	0.9900
11:67373521:TACCT:T	donor_loss	0.9900
11:67373522:A:AT	donor_loss	0.9900
11:67373523:C:CA	donor_loss	0.9900
11:67373523:CCT:C	donor_loss	0.9900
11:67373523:CCTG:C	donor_gain	0.9900
19:39731502:TTAC:T	acceptor_gain	0.9900

AlphaMissense

1444 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67365242:A:G	L191P	0.999
11:67365496:G:C	N106K	0.999
11:67365496:G:T	N106K	0.999
11:67365592:G:C	F74L	0.999
11:67365592:G:T	F74L	0.999
11:67365594:A:G	F74L	0.999
11:67365607:G:C	F69L	0.999
11:67365607:G:T	F69L	0.999
11:67365609:A:G	F69L	0.999
11:67365209:A:G	F202S	0.998
11:67365213:C:G	D201H	0.998
11:67365221:G:C	S198W	0.998
11:67365225:G:T	R197S	0.998
11:67365280:G:C	F178L	0.998
11:67365280:G:T	F178L	0.998
11:67365282:A:G	F178L	0.998
11:67365386:A:G	L143P	0.998
11:67365506:A:G	L103P	0.998
11:67365532:C:A	W94C	0.998
11:67365532:C:G	W94C	0.998
11:67365534:A:G	W94R	0.998
11:67365534:A:T	W94R	0.998
11:67365593:A:G	F74S	0.998
11:67365608:A:G	F69S	0.998
11:67367482:A:G	L54P	0.998
11:67367494:A:G	L50P	0.998
11:67367506:A:G	L46P	0.998
11:67365222:A:G	S198P	0.997
11:67365230:A:G	L195P	0.997
11:67365234:A:G	W194R	0.997

dbSNP variants (sampled 300 via entrez): RS1000576087 (11:67372004 G>A), RS1000684726 (11:67366223 G>A,T), RS1000809641 (11:67372533 C>G), RS1000907971 (11:67372306 G>A,T), RS1001550263 (11:67371383 C>T), RS1001600874 (11:67371642 G>C), RS1001669598 (11:67373212 G>A), RS1001719096 (11:67365630 G>C), RS1001828500 (11:67372407 G>C), RS1001882444 (11:67372725 G>A,C,T), RS1001972340 (11:67373527 C>A), RS1002272833 (11:67366821 G>A,T), RS1003206602 (11:67363908 T>G), RS1003340331 (11:67374998 T>C,G), RS1003643346 (11:67375703 C>T)

Disease associations

OMIM: gene MIM:607672 | disease phenotypes: MIM:610313

GenCC curated gene-disease

Disease	Classification	Inheritance
cold-induced sweating syndrome 2	Strong	Autosomal recessive
Cold-induced sweating syndrome 1	Supportive	Autosomal recessive
cold-induced sweating syndrome	Supportive	Autosomal recessive

Mondo (3): cold-induced sweating syndrome 2 (MONDO:0012467), Cold-induced sweating syndrome 1 (MONDO:0010091), cold-induced sweating syndrome (MONDO:0015526)

Orphanet (1): Cold-induced sweating syndrome (Orphanet:157820)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000293	Full cheeks
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000411	Protruding ear
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000966	Hypohidrosis
HP:0000975	Hyperhidrosis
HP:0001250	Seizure
HP:0001276	Hypertonia
HP:0001371	Flexion contracture
HP:0001376	Limitation of joint mobility
HP:0001377	Limited elbow extension
HP:0001522	Death in infancy
HP:0001645	Sudden cardiac death
HP:0002047	Malignant hyperthermia
HP:0002093	Respiratory insufficiency
HP:0002650	Scoliosis
HP:0002808	Kyphosis
HP:0002938	Lumbar hyperlordosis
HP:0002944	Thoracolumbar scoliosis
HP:0002967	Cubitus valgus
HP:0004691	2-3 toe syndactyly
HP:0007141	Sensorimotor neuropathy
HP:0011968	Feeding difficulties
HP:0025278	Cold-induced sweating
HP:0030084	Clinodactyly

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007293_14	Body fat distribution (arm fat ratio)	9.000000e-08
GCST007294_129	Body fat distribution (trunk fat ratio)	8.000000e-28
GCST007294_95	Body fat distribution (trunk fat ratio)	1.000000e-35
GCST007295_43	Body fat distribution (leg fat ratio)	1.000000e-25
GCST007295_76	Body fat distribution (leg fat ratio)	1.000000e-21

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536214	Crisponi syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Estradiol	affects cotreatment, increases expression, affects binding, decreases expression	3
Tobacco Smoke Pollution	increases expression, affects expression	3
bisphenol A	decreases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	affects cotreatment, decreases expression	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Nickel	increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
GSK-J4	decreases expression	1
Glupearl 19S	increases expression	1
TL8-506	affects cotreatment, increases expression	1
lead acetate	increases expression	1
sodium arsenate	increases abundance, increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	decreases expression	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
cetrorelix	decreases expression	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
NSC668394	increases expression	1
Temozolomide	decreases expression	1
Decitabine	increases expression	1
Leflunomide	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_ZL84	UKMi002-A	Induced pluripotent stem cell	Male
CVCL_ZL85	UKMi002-B	Induced pluripotent stem cell	Male
CVCL_ZL86	UKMi002-C	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.