CLEC19A

Chr 16

C-type lectin domain containing 19A

NCBI Gene: 728276 ENSG00000261210 UniProt: Q6UXS0

The protein is predicted to bind carbohydrates and localize to the extracellular region. Mutations in this gene have been associated with neurodevelopmental disorders, though the clinical phenotype and inheritance pattern are not well-established based on current data. The gene shows relatively low constraint to loss-of-function variation.

ResearchSummary from RefSeq

Predicted to enable carbohydrate binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.60

Clinical Summary— CLEC19A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 total variants — no pathogenic classifications of 7 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.60LOEUF

pLI 0.004

Z-score 0.56

OE 0.74 (0.36–1.60)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.81Z-score

OE missense 0.73 (0.58–0.92)

51 obs / 70.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.36–1.60)

0≤0.351.4

Missense OE?0.73 (0.58–0.92)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 4 / 5.4Missense obs/exp: 51 / 70.2Syn Z: 0.63

This gene — mechanism propensity

0.7229th %ile

GOF

0.7029th %ile

LOF

0.2583th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

7 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign1

Benign1

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Synonymous	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	0	0
Likely Benign	1	1
Benign	1	1
Total	2	2

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap CLEC19A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →