IL10

Chr 1

interleukin 10

Also known as: CSIF, GVHDS, IL-10, IL10A, TGIF

NCBI Gene: 3586 ENSG00000136634 UniProt: P22301

The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. [provided by RefSeq, May 2020]

Primary Disease Associations & Inheritance

{Graft-versus-host disease, protection against}MIM #614395

{HIV-1, susceptibility to}MIM #609423

{Rheumatoid arthritis, progression of}MIM #180300

Active trials

Pathogenic / LP

160

ClinVar variants

Pubs (1 yr)

0.8

Missense Z

1.04

LOEUF

Clinical Summary— IL10

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Gene-Disease Validity (ClinGen)

immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

16 Pathogenic / Likely Pathogenic· 65 VUS of 160 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.04LOEUF

pLI 0.006

Z-score 1.49

OE 0.49 (0.26–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.84Z-score

OE missense 0.76 (0.62–0.92)

71 obs / 93.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.49 (0.26–1.04)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.62–0.92)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00

0≤1.21.6

LoF obs/exp: 5 / 10.1Missense obs/exp: 71 / 93.9Syn Z: -0.02

0.79top 25%

GOF

0.72top 25%

LOF

0.2091th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15

Likely Pathogenic1

VUS65

Likely Benign67

Benign11

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	15	0	15
Likely Pathogenic	0	0	1	0	1
VUS	0	53	12	0	65
Likely Benign	0	1	25	41	67
Benign	0	0	11	0	11
Conflicting	—				1
Total	0	54	64	41	160

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IL10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

COVID-19Antibody COVID-19

The Role of Obesity in Severe COVID-19 Pathophysiology

RECRUITING

NCT06968442Phase NAFranciscus GasthuisStarted 2025-04-22

Venipuncture

Multiple SclerosisSpasticity

miR-142-3p as Potential Biomarker of Synaptopathy in MS

RECRUITING

NCT03999788Phase NANeuromed IRCCSStarted 2019-12-10

lumbar puncture and blood withdrawalIntermittent theta burst stimulation (iTBS) therapeutic protocol for spasticity

Systemic Lupus ErythematosusRheumatoid ArthritisMultiple Sclerosis

Quantum-Synaptic Immunotherapy Mapping Using Low-Frequency Electromagnetic Resonance and Machine Learning-Based Cytokine Forecasting

ENROLLING BY INVITATION

NCT07221565Phase PHASE1, PHASE2Truway Health, Inc.Started 2025-10-23

Low-Frequency Electromagnetic Resonance Therapy (LF-EMR)Sham Resonance Device (Inactive Control)Low-Dose Naltrexone (LDN)

Multiple Sclerosis

This is an Early Exploratory Study to Assess the Tolerability and Safety of GC012F in Patients With Multiple Sclerosis

RECRUITING

NCT07303790Phase EARLY_PHASE1Daishi TianStarted 2026-01-16

GC012F CAR-T Cell Injection

Migraine DisordersPainAutoimmune Diseases

The Role of Cytokines and Regulatory T Lymphocytes in Migraine Pathophysiology.

RECRUITING

NCT06426316Phase NAUniversity Hospital, Clermont-FerrandStarted 2025-06-02

Blood test

Depression

Intern Health Study

ENROLLING BY INVITATION

NCT01809080University of MichiganStarted 2007-05

Low Back Pain

The Prognostic Value of Biomarkers and the Effect of Tolperisone in Acute Low Back Pain and Sciatic Pain "BETA"

ACTIVE NOT RECRUITING

NCT05544656Phase PHASE3Semmelweis UniversityStarted 2019-12-13

Tolperisone HydrochloridePlacebo

Sickle Cell Disease

Cannabinoids for the Reduction of Inflammation and Sickle Cell Related Pain

RECRUITING

NCT05519111Phase PHASE2Icahn School of Medicine at Mount SinaiStarted 2025-04-03

DronabinolPlacebo

Stress (Psychology)InflamationPsychosocial Functioning

A Mindfulness-Based Intervention to Reduce Stress Through the Cultivation of Loving-Kindness, Compassion, Joy, and Equanimity in Healthcare Professionals

RECRUITING

NCT07283744Phase NAUniversity of California, Los AngelesStarted 2025-10-10

Building Emotional Strength Training

Periodontal Disease (PD)Cardio Vascular DiseaseOral-Systemic Link

PMPR and Chlorhexidine on Periodontal Disease and Vascular Function

NOT YET RECRUITING

NCT07311512Phase NAMahdi MutaharStarted 2026-01-23

Chlorhexidine (0.2%) mouthwashPlacebo mouthwash

Systemic Lupus Erythematosus (SLE)Idiopathic Inflammatory Myopathy (IIM)Systemic Sclerosis (SSc)

Safety Study of CC312 in Autoimmune Disease Patients

RECRUITING

NCT06888960Phase EARLY_PHASE1CytoCares IncStarted 2024-11-08