BICD2

Chr 9AD

BICD cargo adaptor 2

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

NCBI Gene: 23299ENSG00000185963UniProt: Q8TD16

This gene is one of two human homologs of Drosophila bicaudal-D and a member of the Bicoid family. It has been implicated in dynein-mediated, minus end-directed motility along microtubules. It has also been reported to be a phosphorylation target of NIMA related kinase 8. Two alternative splice variants have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominantMIM #615290
AD
Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominantMIM #618291
AD
592
ClinVar variants
27
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
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
27 Pathogenic / Likely Pathogenic· 293 VUS of 592 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.07–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.68–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 4 / 30.0Missense obs/exp: 414 / 561.0Syn Z: -0.45

ClinVar Variant Classifications

592 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic13
VUS293
Likely Benign223
Benign22
Conflicting27
14
Pathogenic
13
Likely Pathogenic
293
VUS
223
Likely Benign
22
Benign
27
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
7
0
14
Likely Pathogenic
0
10
3
0
13
VUS
5
254
33
1
293
Likely Benign
0
44
40
139
223
Benign
0
4
9
9
22
Conflicting
—27
Total531992149592

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.

Gene2Phenotype Curations

BICD2-related proximal spinal muscular atrophy with brain anomalies

definitive
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant

MIM #615290

Molecular basis of disorder known

Autosomal dominant

Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant

MIM #618291

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Systemic Sclerosis-Specific Antibodies: Novel and Classical Biomarkers.
Cavazzana I et al.·Clin Rev Allergy Immunol
2023
Distal hereditary motor neuropathies.
Tazir M et al.·Rev Neurol (Paris)
2024Review
Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice.
Xiu J et al.·Proc Natl Acad Sci U S A
2022Cohort
Genetic overlap between ALS and other neurodegenerative or neuromuscular disorders.
Olsen CG et al.·Amyotroph Lateral Scler Frontotemporal Degener
2024
The Genotypic and Phenotypic Spectrum of BICD2 Variants in Spinal Muscular Atrophy.
Koboldt DC et al.·Ann Neurol
2020Review
Clinical spectrum of BICD2 mutations.
Frasquet M et al.·Eur J Neurol
2020
Comprehensive multiplexed autoantibody profiling of patients with advanced urothelial cancer.
Ravi P et al.·J Immunother Cancer
2024Cohort
Neurogenic arthrogryposis and the power of phenotyping.
Rossor AM et al.·Neuromuscul Disord
2021Review
Likely pathogenic variant in the BICD2 gene in fetus presenting with non-immune hydrops.
Chandler N et al.·Prenat Diagn
2023Case report
Genetic epidemiology of amyotrophic lateral sclerosis in Cyprus: a population-based study.
Mitsi E et al.·Sci Rep
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Antisense oligonucleotide of cargo adaptor BICD2 long-term effectively alleviates neuropathic pain via activation of PSD95 in the mouse spinal dorsal horn.
Wu ZX et al.·Neuropharmacology
2026Functional
Dominant spinal muscular atrophy linked mutations in the cargo binding domain of BICD2 result in altered interactomes and dynein hyperactivity.
Neiswender H et al.·Elife
2025🔓 Open Access
BICD2 promotes ciliogenesis by facilitating CP110 removal from the mother centriole.
Kuang W et al.·EMBO Rep
2025🔓 Open Access
Rab6a enables BICD2/dynein-mediated trafficking of human papillomavirus from the trans-Golgi network during virus entry.
Choi J et al.·mBio
2024🔓 Open Access
Missense BICD2 variants in fetuses with congenital arthrogryposis and pterygia.
Masuda L et al.·Hum Genome Var
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools