BICDL2

Chr 16

BICD family like cargo adaptor 2

Also known as: BICDR-2, BICDR2, CCDC64B

NCBI Gene: 146439 ENSG00000162069 UniProt: A1A5D9 OMIM: 617003

The protein is predicted to bind small GTPases and transport vesicles along microtubules from the Golgi to secretory granules. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), suggesting that mutations would likely cause severe developmental disorders, though specific disease associations have not yet been established. The inheritance pattern for potential BICDL2-related disorders has not been determined.

OMIM ResearchSummary from RefSeq

Predicted to enable small GTPase binding activity. Predicted to be involved in Golgi to secretory granule transport and vesicle transport along microtubule. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.12

Clinical Summary— BICDL2

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.12LOEUF

pLI 0.000

Z-score 1.07

OE 0.78 (0.55–1.12)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.51Z-score

OE missense 1.08 (0.99–1.19)

312 obs / 287.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.78 (0.55–1.12)

0≤0.351.4

Missense OE?1.08 (0.99–1.19)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 21 / 27.0Missense obs/exp: 312 / 287.6Syn Z: 0.03

This gene — mechanism propensity

0.75top 25%

GOF

0.6737th %ile

LOF

0.3068th %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.