DCBLD2

Chr 3

discoidin, CUB and LCCL domain containing 2

Also known as: CLCP1, ESDN

DCBLD2 encodes a cell surface signaling receptor that negatively regulates cell growth and participates in wound healing processes. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants (LOEUF 0.446), suggesting intolerance to protein-truncating mutations.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 0.45
Clinical SummaryDCBLD2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.095
Z-score 4.09
OE 0.26 (0.150.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.95Z-score
OE missense 0.87 (0.800.95)
360 obs / 414.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.150.45)
00.351.4
Missense OE0.87 (0.800.95)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 9 / 35.2Missense obs/exp: 360 / 414.6Syn Z: 0.09
DN
0.7229th %ile
GOF
0.78top 25%
LOF
0.3164th %ile

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

GOFprediction above median
DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DCBLD2 · 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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