IL37

protein-coding

interleukin 37, the group of Interleukins

Gene summary

The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine can bind to, and may be a ligand for interleukin 18 receptor (IL18R1/IL-1Rrp). This cytokine also binds to interleukin 18 binding protein (IL18BP), an inhibitory binding protein of interleukin 18 (IL18), and subsequently forms a complex with IL18 receptor beta subunit, and through which it inhibits the activity of IL18. This gene along with eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Five alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Previous symbols:

IL1F7

MANE transcript

NM_014439.4

Inheritance

ClinVar variants

P:3U:24B:5

Top phenotype

Inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr2:112,911,165-112,918,882

External References & Databases

Ensembl (ENSG00000125571)

Transcript & Mutation Effects

hg38 • Region Span ~7.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessiveLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030314

Submitter: Labcorp Genetics (formerly Invitae)

inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030314

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessiveAR

Manifestation: Allergy/Immunology/Infectious; Gastrointestinal

Intervention: Allergy/Immunology/Infectious; Gastrointestinal

Rationale: The condition can manifest with inflammatory bowel disease, and medical management (eg, with mesalamine, corticosteroids, and azathioprine) have been described as being beneficial

Refs: 33674380

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IL37 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 5

Inflammatory bowel disease (infantile ulcerative colitis) 31, autosomal recessiveTotal: 3

Inflammatory bowel diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014439.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense	1 clinvar		23 clinvar	3 clinvar	1 clinvar	28
nonsense		2 clinvar				2
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	2	24	4	1	32

Highest pathogenic variant AF is 0.00013013765

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014439.4	RefSeq	NP_055254.2	5	MANE Select
ENST00000263326.8	Ensembl	ENSP00000263326.3	5	MANE Select
NM_173202.2	RefSeq	NP_775294.1	4	Standard
NM_173203.2	RefSeq	NP_775295.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by Interleukins
Cytokine Signaling in Immune system
Interleukin-18 signaling
Immune System
Interleukin-37 signaling

Biological Process

inflammatory response
immune response
regulation of signaling receptor activity
cytokine-mediated signaling pathway
neutrophil chemotaxis

Molecular Function

cytokine activity
interleukin-1 receptor binding

Cellular Component

extracellular region
extracellular space
nucleoplasm
cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263326
Coding exons: 5
Length: 5912
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125736
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0421	119	118	1.01	0.00000593	1438
Missense (PolyPhen)		26	24.045	1.0813		347
Synonymous	-0.679	53	47.1	1.13	0.00000268	402
Loss of Function	0.131	6	6.36	0.944	2.65e-7	91

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation. {ECO:0000269|PubMed:18390730, ECO:0000269|PubMed:20935647}.;

Recessive Scores

pRec: 0.0767

Intolerance Scores

RVIS EVS: 1.62
RVIS percentile EVS: 95.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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