CLEC16A

Chr 16

C-type lectin domain containing 16A

Also known as: Gop-1, KIAA0350

This protein regulates mitophagy (selective mitochondrial autophagy) through the RNF41-PRKN pathway, which is essential for mitochondrial quality control and beta cell function. The gene is highly constrained against loss-of-function variants (LOEUF 0.38), and mutations cause autosomal recessive primary immunodeficiency with diabetes mellitus and neurodegeneration. Clinical features include early-onset diabetes, immunodeficiency, and progressive neurological deterioration affecting multiple systems.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.38
Clinical SummaryCLEC16A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 164 VUS of 235 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.276
Z-score 4.91
OE 0.23 (0.140.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.21Z-score
OE missense 0.86 (0.810.93)
549 obs / 635.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.140.38)
00.351.4
Missense OE0.86 (0.810.93)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 11 / 47.5Missense obs/exp: 549 / 635.2Syn Z: -2.16

ClinVar Variant Classifications

235 submitted variants in ClinVar

Classification Summary

Pathogenic18
VUS164
Likely Benign18
Benign1
18
Pathogenic
164
VUS
18
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
0
0
0
VUS
0
152
12
0
164
Likely Benign
0
9
2
7
18
Benign
0
1
0
0
1
Total0162327201

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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