C17ORF99

Chr 17

chromosome 17 open reading frame 99

Also known as: IL-40, IL40, UNQ464

NCBI Gene: 100141515ENSG00000187997UniProt: Q6UX52

Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in cell surface receptor signaling pathway; mature B cell differentiation involved in immune response; and positive regulation of immunoglobulin production in mucosal tissue. Located in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]

1
Active trials
13
Pathogenic / LP
16
ClinVar variants
0
Pubs (1 yr)
0.9
Missense Z
0.79
LOEUF
Clinical Summary— C17ORF99
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 2 VUS of 16 total submissions
💊
Clinical Trials
1 active or recruiting trial — 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.
0.79LOEUF
pLI 0.132
Z-score 2.01
OE 0.31 (0.14–0.79)
Tolerant

Typical tolerance to LoF variation

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.
0.94Z-score
OE missense 0.78 (0.67–0.91)
110 obs / 141.4 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.0.31 (0.14–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.67–0.91)
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.0.89
0≤1.21.6
LoF obs/exp: 3 / 9.8Missense obs/exp: 110 / 141.4Syn Z: 0.68

ClinVar Variant Classifications

16 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
VUS2
Likely Benign1
13
Pathogenic
2
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————13
Likely Pathogenic
————0
VUS
————2
Likely Benign
————1
Benign
————0
Total—16

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

C17ORF99 · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Comparative Response of HCC Cells to TKIs: Modified in vitro Testing and Descriptive Expression Analysis
Sagmeister P et al.·J Hepatocell Carcinoma
2022
Possible role for IL-40 and IL-40-producing cells in the lymphocytic infiltrated salivary glands of patients with primary Sjogren's syndrome
Guggino G et al.·RMD Open
2023Cohort
A Comprehensive Review on the Role of Interleukin-40 as a Biomarker for Diagnosing Inflammatory Diseases
Dabbagh-Gorjani F·Autoimmune Dis
2024Review
CRISPR activation screening in a mouse model for drivers of hepatocellular carcinoma growth and metastasis
Zhang B et al.·iScience
2023Functional
IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis
Navrátilová A et al.·Front Immunol
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

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