CLEC16A

Chr 16

C-type lectin domain containing 16A

Also known as: Gop-1, KIAA0350

NCBI Gene: 23274 ENSG00000038532 UniProt: Q2KHT3 OMIM: 611303

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.38

Clinical Summary— CLEC16A

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

152 VUS of 203 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.21Z-score

OE missense 0.86 (0.81–0.93)

549 obs / 635.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.14–0.38)

0≤0.351.4

Missense OE?0.86 (0.81–0.93)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 11 / 47.5Missense obs/exp: 549 / 635.2Syn Z: -2.16

ClinVar Variant Classifications

203 submitted variants in ClinVar

ClinVar

Classification Summary

VUS152

Likely Benign16

Benign1

152

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	152	0	152
Likely Benign	9	7	16
Benign	1	0	1
Total	162	7	169

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap CLEC16A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →