IL17F

Summary

IL17F (interleukin 17F, HGNC:16404) is a protein-coding gene on chromosome 6p12.2, encoding Interleukin-17F (Q96PD4). Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity.

The protein encoded by this gene is a cytokine that shares sequence similarity with IL17. This cytokine is expressed by activated T cells, and has been shown to stimulate the production of several other cytokines, including IL6, IL8, and CSF2/GM_CSF. This cytokine is also found to inhibit the angiogenesis of endothelial cells and induce endothelial cells to produce IL2, TGFB1/TGFB, and monocyte chemoattractant protein-1.

Source: NCBI Gene 112744 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chronic mucocutaneous candidiasis (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 178 total
• Phenotypes (HPO): 33
• Druggable target: yes
• MANE Select transcript: NM_052872

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16404
Approved symbol	IL17F
Name	interleukin 17F
Location	6p12.2
Locus type	gene with protein product
Status	Approved
Aliases	IL-17F, ML-1, ML1
Ensembl gene	ENSG00000112116
Ensembl biotype	protein_coding
OMIM	606496
Entrez	112744

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000336123, ENST00000478427, ENST00000699946

RefSeq mRNA: 1 — MANE Select: NM_052872 NM_052872

CCDS: CCDS4938

Canonical transcript exons

ENST00000336123 — 3 exons

Exon	Start	End
ENSE00001167022	52238730	52238950
ENSE00001424697	52244397	52244500
ENSE00003562963	52236681	52237168

Expression profiles

Bgee: expression breadth broad, 43 present calls, max score 87.14.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.14	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.59	gold quality
endothelial cell	CL:0000115	62.68	gold quality
bone marrow cell	CL:0002092	59.18	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	57.38	gold quality
trabecular bone tissue	UBERON:0002483	56.19	gold quality
vermiform appendix	UBERON:0001154	56.11	gold quality
nasal cavity epithelium	UBERON:0005384	55.72	gold quality
cartilage tissue	UBERON:0002418	54.01	gold quality
colonic epithelium	UBERON:0000397	53.64	silver quality
caecum	UBERON:0001153	52.58	gold quality
parotid gland	UBERON:0001831	52.44	gold quality
decidua	UBERON:0002450	51.62	gold quality
deltoid	UBERON:0001476	48.81	gold quality
tonsil	UBERON:0002372	48.40	gold quality
vastus lateralis	UBERON:0001379	46.71	gold quality
bone marrow	UBERON:0002371	46.63	gold quality
quadriceps femoris	UBERON:0001377	46.55	gold quality
biceps brachii	UBERON:0001507	46.33	gold quality
middle temporal gyrus	UBERON:0002771	46.30	gold quality
lateral nuclear group of thalamus	UBERON:0002736	46.18	gold quality
lateral globus pallidus	UBERON:0002476	46.00	gold quality
skeletal muscle tissue	UBERON:0001134	45.48	gold quality
colonic mucosa	UBERON:0000317	45.18	gold quality
gingiva	UBERON:0001828	44.47	gold quality
buccal mucosa cell	CL:0002336	43.74	gold quality
substantia nigra pars compacta	UBERON:0001965	43.61	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	43.36	gold quality
muscle tissue	UBERON:0002385	43.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETV5, EZH2, GFI1, HNF1A, NFATC1, PRDM1, RORA, RORC, STAT3, TBX21

miRNA regulators (miRDB)

20 targeting IL17F, 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-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-144-5P	97.66	69.90	531
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-6861-5P	96.23	67.19	800

Literature-anchored findings (GeneRIF, showing 40)

• a cytokine involved in the activaion of MAP kinases (PMID:11891214)
• cell membrane IL-17R is required for signaling by both IL-17A and IL-17F (PMID:15972674)
• This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6. (PMID:17346928)
• IL-17F induces expression of IFN-gamma-inducible protein 10 (IP-10) by activating Raf1-mitogen-activated protein kinase 1/2-extracellular-regulated kinase 1/2-p90 ribosomal S6 kinase-cyclic AMP response element-binding protein signaling pathway. (PMID:17418381)
• Our results provided the first evidence that -197A (IL-17A) and 7488T (IL-17F) alleles may influence the susceptibility to and pathophysiological features of ulcerative colitis independently. (PMID:17828618)
• These results provide the first evidence that the IL-17F and MIF gene polymorphisms are significantly associated with the development of functional dyspepsia. (PMID:17912466)
• Intestinal IL17F gene expression is increased in active CD (PMID:18088064)
• Human IL-17F/IL-17A heterodimer can bind and signal through the same receptor complex as human homodimeric cytokines IL-17F and IL-17A. (PMID:18684971)
• The association between chronic fatigue syndrome and the frequency of rs763780, a C/T genetic polymorphism leading to His161Arg substitution in the IL-17F protein was studied. (PMID:18774769)
• IL-17F may be involved in psoriasis via, in part, the activation of ERK1/2 and the induction of IL-8 in keratinocytes (PMID:18830271)
• IL-17F single nucleotide polymorphism is not associated with psoriasis vulgaris or atopic dermatitis in the Japanese population. (PMID:19019635)
• Although transgenic strain IL-17F expression is restricted to CD4-positive T cells during murine experimental autoimmune encephalomyelitis, CD8 T cells robustly express IL-17F. (PMID:19155467)
• This study shows that IL-17F 7488 A > G polymorphism is associated with weak UC protection in the Chinese population. (PMID:19263269)
• Results show that G-197A polymorphism of IL-17A gene was significantly associated with the development of gastric cancer, especially intestinal-type cancer. (PMID:19414056)
• No association were found between CpG island hyper-methylati status and L-17A (-197G>A), IL-17F (7488T>C) and MIF (-173G>C) polymorphism. (PMID:19724898)
• The IL-17F His161Arg polymorphism is unlikely to be a major contributor to the pathogenesis of myocardial infarction. (PMID:19838108)
• present the crystal structure of a complex of IL-17 receptor A (IL-17RA) bound to IL-17F in a 1:2 stoichiometry. (PMID:19838198)
• Results suggest that genetic polymorphisms of IL-17A and MIF, but not IL-17F, are associated with CpG island hyper-methylation status in gastric cancer. (PMID:20127054)
• produced by CD4+ T cells in psoriatic skin lesions (PMID:20148256)
• IL-17F, a novel antiangiogenic factor, directly inhibited ECV304 vascular endothelial cell growth and downregulated the expression of proangiogenic factors IL-6, IL-8, and VEGF in hepatocarcinoma cells. (PMID:20210523)
• IL-17 isoforms (IL-17A and IL-17F) are implicated in systemic lupus erythematosus but also in discoid and subacute lupus erythrmatosis immunopathogenesis (PMID:20493423)
• investigated the association between rheumatoid arthritis (RA) and His161Arg (7488A/G; rs763780) and Glu126Gly (7383A/G; rs2397084) polymorphism of IL-17F gene; results showed the relationship between IL-17F gene polymorphisms and severity of RA (PMID:20618772)
• genetic polymorphism is associated with Vogt-Koyanagi-Harada syndrome but not with Behcet’s disease in a Chinese Han population (PMID:20620187)
• H. pylori infection leads to a strong upregulation of both IL-17A and IL-17F in the gastric mucosa suggesting a regulatory link between both genes. (PMID:21044126)
• a twenty-fold increase in the expression of IL-17A mRNA and thirty three-times greater expression of IL-17F in Multiple sclerosis patients compared to the control group (PMID:21189442)
• gene polymorphism is associated with susceptibility to asthma in a Korean population (PMID:21196754)
• After renaturation and purification of IL-17F, the recombinant protein can up-regulate macrophages to secret TNF-alpha, IL-6 and other relative cytokines. It also promoted proliferation of HeLa cells in vitro. (PMID:21419044)
• CD8-positive T-cells express IL-17F which may be involved in the pathogenesis of chronic obstructive pulmonary disease. (PMID:21477350)
• These findings suggest that IL-17F may stimulate the development of endometriosis by up-regulation of IL-8 and COX2. (PMID:21601196)
• IL-17F 7488 T allele is significantly associated with the development of chronic ITP, suggesting a role for IL-17F in the pathogenesis of chronic immune thrombocytopenia. (PMID:21615796)
• DNA copy number variations of IL-17F, IL-21, and IL-22 are associated with the risk of systemic lupus erythematosus. (PMID:22038405)
• Significantly higher frequencies of the rs763780 T allele and TT genotype of IL17F were observed in neuromyelitis optica patients versus controls (PMID:22118860)
• These novel findings provide evidence that cytokine-stimulated B lymphocytes could be a significant source of IL-17A and IL-17F and support the notion that these cells actively participate in immune responses via alternative mechanisms in addition to the classic release of antibodies. (PMID:22123224)
• The angiogenetic potential of pancreatic cancers in patients with variant IL-17F is higher than that of tumors in patients with wild-type IL-17F, conferring worse prognosis. (PMID:22142827)
• cAMP-responsive element modulator alpha (CREMalpha) suppresses IL-17F protein expression in T lymphocytes from patients with systemic lupus erythematosus (SLE). (PMID:22184122)
• results provide evidence that Th17 cytokines IL-17A and IL-17F have a distinct regulatory role in CXCL1, CXCL5, and CXCL8 expression in lung microvascular endothelial cells stimulated either with IL-1beta or with TNF-alpha (PMID:22219048)
• Of all the SNPs analyzed of IL17A and IL17F, only rs17880588 showed a significant association with asthma in the Saudi population. (PMID:22312940)
• Results suggested that single-nucleotide polymorphisms (SNPs) in IL-17A but not IL-17F were associated with the risk of breast cancer. (PMID:22461912)
• IL17A and IL17F SNPs, and some intergenic variants have the potential association with allergic rhinitis and comorbid asthma in Chinese population. (PMID:22507625)
• data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation (PMID:22540331)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	il17a/f3	ENSDARG00000041976
danio_rerio	il17a/f1	ENSDARG00000043933
danio_rerio	si:dkey-66g10.2	ENSDARG00000092845
mus_musculus	Il17f	ENSMUSG00000041872
rattus_norvegicus	Il17f	ENSRNOG00000012509
caenorhabditis_elegans		WBGENE00009108

Paralogs (5): IL17A (ENSG00000112115), IL17C (ENSG00000124391), IL17B (ENSG00000127743), IL25 (ENSG00000166090), IL17D (ENSG00000172458)

Protein

Protein identifiers

Interleukin-17F — Q96PD4 (reviewed: Q96PD4)

Alternative names: Cytokine ML-1

All UniProt accessions (1): Q96PD4

UniProt curated annotations — full annotation on UniProt →

Function. Effector cytokine of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. IL17A-IL17F signals via IL17RA-IL17RC heterodimeric receptor complex, triggering homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation. IL17A-IL17F is primarily involved in host defense against extracellular bacteria and fungi by inducing neutrophilic inflammation. As signature effector cytokine of T-helper 17 cells (Th17), primarily induces neutrophil activation and recruitment at infection and inflammatory sites. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers. IL17F homodimer can signal via IL17RC homodimeric receptor complex, triggering downstream activation of TRAF6 and NF-kappa-B signaling pathway. Via IL17RC induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi. Likely via IL17RC, promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression. Regulates the composition of intestinal microbiota and immune tolerance by inducing antimicrobial proteins that specifically control the growth of commensal Firmicutes and Bacteroidetes.

Subunit / interactions. Homodimer; disulfide-linked. Heterodimer with IL17A (IL17A-IL17F). Forms complexes with IL17RA and IL17RC receptors with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule. IL17F homodimer forms predominantly complexes with IL17RC homodimer, whereas IL17A-IL17F favors complexes with IL17RA-IL17RC. IL17RA and IL17RC chains cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes.

Subcellular location. Secreted.

Tissue specificity. Expressed in T-helper 1 and T-helper 2 cells, basophils and mast cells.

Disease relevance. Candidiasis, familial, 6 (CANDF6) [MIM:613956] A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the IL-17 family.

RefSeq proteins (1): NP_443104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010345	IL-17_fam	Family
IPR020440	IL-17_chr	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF06083

UniProt features (26 total): strand 9, sequence variant 4, disulfide bond 4, helix 3, turn 2, signal peptide 1, chain 1, mutagenesis site 1, glycosylation site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
6HGO	X-RAY DIFFRACTION	2.1
5N92	X-RAY DIFFRACTION	2.3
6PPG	X-RAY DIFFRACTION	2.75
8RUU	X-RAY DIFFRACTION	2.81
1JPY	X-RAY DIFFRACTION	2.85
3JVF	X-RAY DIFFRACTION	3.3
5NAN	X-RAY DIFFRACTION	3.3
6HG4	X-RAY DIFFRACTION	3.32
6HG9	X-RAY DIFFRACTION	3.62

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PD4-F1	87.75	0.67

Antibody-complex structures (SAbDab): 2 — 6PPG, 8RUU

Functional residue map

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

Disulfide bonds (4): 47, 102–152, 107–154, 137

Glycosylation sites (1): 83

Mutagenesis-validated functional residues (1):

Position	Phenotype
77	significantly decreases the affinity for il17ra and il17rc by nearly 5-fold and 200-fold, respectively.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-448424	Interleukin-17 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses

MSigDB gene sets: 218 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, RACCACAR_AML_Q6, GOBP_POSITIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_SUPERFAMILY_CYTOKINE_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, chr6p12

GO Biological Process (23): positive regulation of cytokine production (GO:0001819), positive regulation of antimicrobial peptide production (GO:0002225), adaptive immune response (GO:0002250), inflammatory response (GO:0006954), negative regulation of angiogenesis (GO:0016525), regulation of transforming growth factor beta receptor signaling pathway (GO:0017015), regulation of granulocyte macrophage colony-stimulating factor production (GO:0032645), regulation of interleukin-2 production (GO:0032663), regulation of interleukin-6 production (GO:0032675), regulation of interleukin-8 production (GO:0032677), positive regulation of interleukin-6 production (GO:0032755), positive regulation of lymphotoxin A production (GO:0032761), innate immune response (GO:0045087), positive regulation of transcription by RNA polymerase II (GO:0045944), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), cartilage development (GO:0051216), interleukin-17-mediated signaling pathway (GO:0097400), positive regulation of cytokine production involved in inflammatory response (GO:1900017), positive regulation of chemokine (C-X-C motif) ligand 1 production (GO:2000340), immune system process (GO:0002376), regulation of primary metabolic process (GO:0080090), positive regulation of tumor necrosis factor superfamily cytokine production (GO:1903557)

GO Molecular Function (6): cytokine activity (GO:0005125), cytokine receptor binding (GO:0005126), cytokine binding (GO:0019955), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	2
SARS-CoV-2-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cytokine production	5
immune response	2
interleukin-6 production	2
positive regulation of cytokine production	2
defense response to bacterium	2
protein dimerization activity	2
cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
positive regulation of production of molecular mediator of immune response	1
positive regulation of antimicrobial humoral response	1
antimicrobial peptide production	1
regulation of antimicrobial peptide production	1
defense response	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
transforming growth factor beta receptor signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to transforming growth factor beta stimulus	1
granulocyte macrophage colony-stimulating factor production	1
regulation of protein metabolic process	1
interleukin-2 production	1
interleukin-8 production	1
regulation of interleukin-6 production	1
lymphotoxin A production	1
regulation of lymphotoxin A production	1
positive regulation of protein metabolic process	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
defense response to symbiont	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
skeletal system development	1
animal organ development	1
connective tissue development	1
cytokine-mediated signaling pathway	1
cellular response to interleukin-17	1
cytokine production involved in inflammatory response	1
regulation of cytokine production involved in inflammatory response	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IL17F	IL17RA	Q96F46	999
IL17F	IL17RC	Q8NAC3	998
IL17F	IL17RE	Q8NFR9	966
IL17F	IL25	Q9H293	957
IL17F	IL22	Q9GZX6	939
IL17F	IL17RB	Q9NRM6	920
IL17F	IL23R	Q5VWK5	914
IL17F	IL1B	P01584	894
IL17F	IL6	P05231	887
IL17F	CD4	P01730	870
IL17F	IL23A	Q9NPF7	869
IL17F	IFNG	P01579	869
IL17F	RORC	P51449	868
IL17F	TBX21	Q9UL17	843
IL17F	IL13	P35225	825

IntAct

17 interactions, top by confidence:

A	B	Type	Score
FLJ13057	IL17F	psi-mi:“MI:0915”(physical association)	0.560
MCRIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
IL17A	IL17F	psi-mi:“MI:0407”(direct interaction)	0.440
IL17RA	IL17F	psi-mi:“MI:0407”(direct interaction)	0.440
IL17RC	IL17F	psi-mi:“MI:0407”(direct interaction)	0.440
PPIL3	SNX3	psi-mi:“MI:0914”(association)	0.350
LDAF1	SLC19A2	psi-mi:“MI:0914”(association)	0.350
IL17F	TBL1X	psi-mi:“MI:0914”(association)	0.350
C20orf141	ENDOD1	psi-mi:“MI:0914”(association)	0.350
SDHD	TNNC2	psi-mi:“MI:0914”(association)	0.350
BRD4	SUMO1	psi-mi:“MI:0914”(association)	0.350
PDPN	KIF14	psi-mi:“MI:0914”(association)	0.350
CCDC28A	BLTP1	psi-mi:“MI:0914”(association)	0.350
IL17F	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): IL17F (Two-hybrid), IL17F (Reconstituted Complex), VWDE (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), IL17F (Affinity Capture-MS), SEC24D (Affinity Capture-MS), IL17F (Affinity Capture-MS), IL17F (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), IL17F (Affinity Capture-MS), PRKCI (Affinity Capture-MS), IL17F (Affinity Capture-MS), HMGCS1 (Affinity Capture-MS), FAT1 (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS)

ESM2 similar proteins: A6N6I9, B0VXV3, B0VXV4, C0K3N1, O40633, O46526, P00683, P0DW98, P24916, P34129, P49764, P50412, P67861, P67862, P67863, Q16552, Q330K6, Q3HRV3, Q3S2X5, Q5BJ95, Q60I29, Q61453, Q62386, Q63434, Q687Y7, Q6J936, Q7TNI7, Q8K4C5, Q8SPN3, Q8SPN4, Q8VD87, Q8VHH8, Q90X23, Q90X24, Q96PD4, Q9D244, Q9P0M4, Q9QXT6, Q9QYX2, Q9QYX3

Diamond homologs: A6N6I9, O40633, P24916, Q16552, Q5BJ95, Q60I29, Q61453, Q62386, Q687Y7, Q7TNI7, Q8TAD2, Q96PD4, Q9EQI6, Q9QXT6, Q9UHF5, A9XE49, Q8K4C5, Q8VHH8, Q9H293, Q9P0M4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	49
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

314 predictions. Top by Δscore:

Variant	Effect	Δscore
6:52238724:ACTT:A	donor_loss	1.0000
6:52238726:TTACG:T	donor_loss	1.0000
6:52238727:TA:T	donor_loss	1.0000
6:52238728:A:AC	donor_gain	1.0000
6:52238729:C:CA	donor_gain	1.0000
6:52238729:CG:C	donor_gain	1.0000
6:52238729:CGT:C	donor_gain	1.0000
6:52238729:CGTG:C	donor_gain	1.0000
6:52238729:CGTGT:C	donor_gain	1.0000
6:52238947:TGAC:T	acceptor_gain	1.0000
6:52238948:GACC:G	acceptor_loss	1.0000
6:52238949:ACC:A	acceptor_loss	1.0000
6:52238951:C:CC	acceptor_gain	1.0000
6:52238952:T:A	acceptor_loss	1.0000
6:52244389:CTACT:C	donor_loss	1.0000
6:52244392:CTCA:C	donor_loss	1.0000
6:52244393:TCA:T	donor_loss	1.0000
6:52244394:CACCA:C	donor_loss	1.0000
6:52244395:A:AC	donor_gain	1.0000
6:52244395:ACC:A	donor_loss	1.0000
6:52244396:C:CC	donor_gain	1.0000
6:52237164:TGACA:T	acceptor_gain	0.9900
6:52237167:CA:C	acceptor_gain	0.9900
6:52237169:C:CC	acceptor_gain	0.9900
6:52238946:TTGAC:T	acceptor_gain	0.9900
6:52238948:GAC:G	acceptor_gain	0.9900
6:52238949:AC:A	acceptor_gain	0.9900
6:52238950:CC:C	acceptor_gain	0.9900
6:52243216:T:C	acceptor_gain	0.9900
6:52244391:ACT:A	donor_loss	0.9900

AlphaMissense

1063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:52238738:C:A	W82C	0.997
6:52238738:C:G	W82C	0.997
6:52237103:C:G	C107S	0.996
6:52237104:A:T	C107S	0.996
6:52237118:C:G	C102S	0.996
6:52237119:A:T	C102S	0.996
6:52236968:C:G	C152S	0.995
6:52236969:A:T	C152S	0.995
6:52237148:C:G	R92P	0.994
6:52237049:T:G	Q125P	0.988
6:52238740:A:G	W82R	0.988
6:52238740:A:T	W82R	0.988
6:52236962:C:T	C154Y	0.987
6:52236969:A:G	C152R	0.987
6:52236962:C:G	C154S	0.986
6:52236963:A:T	C154S	0.986
6:52237055:A:G	I123T	0.986
6:52237119:A:G	C102R	0.986
6:52237034:A:T	V130D	0.985
6:52237104:A:G	C107R	0.983
6:52236961:G:C	C154W	0.982
6:52236963:A:G	C154R	0.982
6:52236971:C:T	G151D	0.982
6:52237055:A:C	I123S	0.982
6:52237055:A:T	I123N	0.981
6:52238752:A:G	S78P	0.981
6:52236972:C:A	G151C	0.980
6:52238754:C:G	R77P	0.980
6:52236967:G:C	C152W	0.979
6:52236971:C:A	G151V	0.979

dbSNP variants (sampled 300 via entrez): RS1000706748 (6:52241210 C>G), RS1000900381 (6:52246891 G>A), RS1001500423 (6:52236734 C>T), RS1001600019 (6:52236332 C>A,T), RS1001681374 (6:52242401 C>G,T), RS1001688037 (6:52239310 A>G), RS1002110839 (6:52242646 A>G), RS1002875617 (6:52246675 G>A), RS1003092746 (6:52243856 A>G), RS1003570788 (6:52238950 C>A,T), RS1003807840 (6:52237255 T>A,C), RS1004057673 (6:52243378 AC>A), RS1004484322 (6:52240424 G>A,C), RS1004620915 (6:52240232 T>G), RS1004759608 (6:52246609 C>A)

Disease associations

OMIM: gene MIM:606496 | disease phenotypes: MIM:613956

GenCC curated gene-disease

Disease	Classification	Inheritance
chronic mucocutaneous candidiasis	Supportive	Autosomal dominant
candidiasis, familial, 6	Limited	Unknown

Mondo (2): candidiasis, familial, 6 (MONDO:0013503), chronic mucocutaneous candidiasis (MONDO:0015279)

Orphanet (1): Chronic mucocutaneous candidiasis (Orphanet:1334)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000142	Abnormal vagina morphology
HP:0000153	Abnormality of the mouth
HP:0000159	Abnormal lip morphology
HP:0000478	Abnormality of the eye
HP:0000504	Abnormality of vision
HP:0000682	Abnormal dental enamel morphology
HP:0000790	Hematuria
HP:0000951	Abnormality of the skin
HP:0000962	Hyperkeratosis
HP:0000988	Skin rash
HP:0000989	Pruritus
HP:0001231	Abnormal fingernail morphology
HP:0001250	Seizure
HP:0001597	Abnormal nail morphology
HP:0001821	Broad nail
HP:0002105	Hemoptysis
HP:0002205	Recurrent respiratory infections
HP:0002715	Abnormality of the immune system
HP:0002719	Recurrent infections
HP:0002728	Chronic mucocutaneous candidiasis
HP:0004306	Abnormal endocardium morphology
HP:0004370	Abnormality of temperature regulation
HP:0008388	Abnormal toenail morphology
HP:0008872	Feeding difficulties in infancy
HP:0010783	Erythema
HP:0012115	Hepatitis
HP:0012735	Cough
HP:0030016	Dyspareunia

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001346_1	Response to gemcitabine in pancreatic cancer	3.000000e-08
GCST004485_52	Survival in pancreatic cancer	3.000000e-08
GCST006633_13	Initial alcohol sensitivity	2.000000e-06
GCST011681_6	Cryptococcosis in HIV infection	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0000638	overall survival

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002178	Candidiasis, Chronic Mucocutaneous	C01.150.703.160.088; C01.150.703.302.100; C01.800.200.100; C17.800.838.208.165; C23.550.291.500.250

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630880 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs763780	IL17F		0.00	0
rs7771466	IL17F		0.00	0

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dihydroouabain	increases secretion, increases expression	1
butyraldehyde	increases expression	1
tryptanthrine	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
Qingdai compound	increases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Digoxigenin	increases expression, increases secretion	1
Latex	increases expression	1
Nickel	increases expression	1
Pentachlorophenol	increases expression	1
Perfume	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Strophanthidin	increases expression, increases secretion	1
Dinoprostone	affects cotreatment, increases expression, increases reaction	1
Simvastatin	decreases secretion	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4828403	Binding	Binding affinity to human IL-17F	Interleukin-17A Peptide Aptamers with an Unexpected Binding Moiety Selected by cDNA Display under Heterogenous Conditions. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01386437	Not specified	RECRUITING	Natural History of Individuals With Immune System Problems That Lead to Fungal Infections
NCT03736252	Not specified	COMPLETED	Effectiveness of a Neoprene CMC Joint Orthosis
NCT05896410	Not specified	UNKNOWN	3D-Printed Hand Orthosis Versus Thermoplastic Orthosis