BICD2

Chr 9AD

BICD cargo adaptor 2

Also known as: SMALED2, SMALED2A, SMALED2B, bA526D8.1

NCBI Gene: 23299ENSG00000185963UniProt: Q8TD16OMIM: 609797

The protein mediates dynein-mediated transport along microtubules toward the minus end and functions at the Golgi apparatus. Loss-of-function mutations cause autosomal dominant spinal muscular atrophy, lower extremity-predominant types 2A and 2B. The high pLI score (0.98) indicates this gene is highly intolerant to loss-of-function variants, consistent with the dominant inheritance pattern where haploinsufficiency drives pathogenicity.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 0.302 OMIM phenotypes
Clinical Summary— BICD2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 22 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.983
Z-score 4.40
OE 0.13 (0.07–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.20Z-score
OE missense 0.74 (0.68–0.80)
414 obs / 561.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.13 (0.07–0.30)
0≤0.351.4
Missense OE0.74 (0.68–0.80)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 4 / 30.0Missense obs/exp: 414 / 561.0Syn Z: -0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBICD2-related proximal spinal muscular atrophy with brain anomaliesOTHERAD
DN
0.5771th %ile
GOF
0.4874th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.30
GOF1 literature citation

Literature Evidence

GOFHere, using biochemical and single-molecule motility assays, we demonstrate that BICD2 disease mutations cause a gain of function in the motility of DDB complexes both in vitro and in cells.PMID:28883039

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic2
VUS22
Likely Benign51
Benign12
Conflicting10
3
Pathogenic
2
Likely Pathogenic
22
VUS
51
Likely Benign
12
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
2
0
3
Likely Pathogenic
0
1
1
0
2
VUS
1
19
2
0
22
Likely Benign
0
12
7
32
51
Benign
0
3
7
2
12
Conflicting
—10
Total1361934100

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

View in ClinVar →

Protein Context — Lollipop Plot

BICD2 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients