CLEC16A

Chr 16

C-type lectin domain containing 16A

Also known as: Gop-1, KIAA0350

NCBI Gene: 23274ENSG00000038532UniProt: Q2KHT3

This gene encodes a member of the C-type lectin domain containing family. Single nucleotide polymorphisms in introns of this gene have been associated with diabetes mellitus, multiple sclerosis and rheumatoid arthritis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

UniProtType 1 diabetes mellitus
235
ClinVar variants
16
Pathogenic / LP
0.28
pLI score
0
Active trials
Clinical Summary— CLEC16A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 73 VUS of 235 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.38LOEUF
pLI 0.276
Z-score 4.91
OE 0.23 (0.14–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.21Z-score
OE missense 0.86 (0.81–0.93)
549 obs / 635.2 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.0.23 (0.14–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.81–0.93)
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.1.16
0≤1.21.6
LoF obs/exp: 11 / 47.5Missense obs/exp: 549 / 635.2Syn Z: -2.16

ClinVar Variant Classifications

235 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
VUS73
Likely Benign11
Benign1
16
Pathogenic
73
VUS
11
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
0
0
0
VUS
0
62
11
0
73
Likely Benign
0
6
2
3
11
Benign
0
1
0
0
1
Total069293101

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

View in ClinVar →

Protein Context — Lollipop Plot

CLEC16A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CLEC16A-An Emerging Master Regulator of Autoimmunity and Neurodegeneration.
Pandey R et al.·Int J Mol Sci
2023Review
CLEC16A interacts with retromer and TRIM27, and its loss impairs endosomal trafficking and neurodevelopment.
Smits DJ et al.·Hum Genet
2023
Defining Mechanistic Links Between the Non-Coding Variant rs17673553 in CLEC16A and Lupus Susceptibility.
Rallabandi HR et al.·Int J Mol Sci
2025
An intrinsically disordered protein region encoded by the human disease gene CLEC16A regulates mitophagy.
Gingerich MA et al.·Autophagy
2023
Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency.
Bronson PG et al.·Nat Genet
2016Meta-analysis
Human Leukocyte Antigen Signatures as Pathophysiological Discriminants of Microscopic Colitis Subtypes.
Zheng T et al.·J Crohns Colitis
2024Meta-analysis
Genetic variations in autoimmune genes and VKH disease.
Albalawi AM et al.·Int Ophthalmol
2020Review
Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells.
Leikfoss IS et al.·PLoS One
2015
Systemic Lupus Erythematosus Patients Exhibit Reduced Expression of CLEC16A Isoforms in Peripheral Leukocytes.
Tam RC et al.·Int J Mol Sci
2015Cohort
Tshz1 Regulates Pancreatic β-Cell Maturation.
Raum JC et al.·Diabetes
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools