IL17A

Chr 6

interleukin 17A

Also known as: CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17

NCBI Gene: 3605 ENSG00000112115 UniProt: Q16552

This gene is a member of the IL-17 receptor family which includes five members (IL-17RA-E) and the encoded protein is a proinflammatory cytokine produced by activated T cells. IL-17A-mediated downstream pathways induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins. The encoded protein elicits crucial impacts on host defense, cell trafficking, immune modulation, and tissue repair, with a key role in the induction of innate immune defenses. This cytokine stimulates non-hematopoietic cells and promotes chemokine production thereby attracting myeloid cells to inflammatory sites. This cytokine also regulates the activities of NF-kappaB and mitogen-activated protein kinases and can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). IL-17A plays a pivotal role in various infectious diseases, inflammatory and autoimmune disorders, and cancer. High levels of this cytokine are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis. The lung damage induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL17A. [provided by RefSeq, Sep 2020]

ClinVar variants

Pathogenic / LP

0.04

pLI score

Active trials

Clinical Summary— IL17A

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

11 Pathogenic / Likely Pathogenic· 25 VUS of 43 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.

1.14LOEUF

pLI 0.043

Z-score 1.35

OE 0.44 (0.20–1.14)

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.

0.28Z-score

OE missense 0.92 (0.77–1.10)

85 obs / 92.4 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.0.44 (0.20–1.14)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.77–1.10)

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.1.32

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	9	0	9
Likely Pathogenic	0	2	0	2
VUS	23	2	0	25
Likely Benign	1	0	0	1
Benign	0	5	1	6
Total	24	18	1	43

IL17A

Population Genetics & Constraint

ClinVar Variant Classifications

Classification Summary

Curated Variants Distribution

Protein Context — Lollipop Plot

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases

Gene Resources