BICD2

Summary

BICD2 (BICD cargo adaptor 2, HGNC:17208) is a protein-coding gene on chromosome 9q22.31, encoding Protein bicaudal D homolog 2 (Q8TD16). Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin.

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.

Source: NCBI Gene 23299 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 963 total — 13 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 89
• MANE Select transcript: NM_001003800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17208
Approved symbol	BICD2
Name	BICD cargo adaptor 2
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0699
Ensembl gene	ENSG00000185963
Ensembl biotype	protein_coding
OMIM	609797
Entrez	23299

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000356884, ENST00000375512

RefSeq mRNA: 2 — MANE Select: NM_001003800 NM_001003800, NM_015250

CCDS: CCDS35064, CCDS6700

Canonical transcript exons

ENST00000356884 — 7 exons

Exon	Start	End
ENSE00000869912	92729024	92729236
ENSE00000869913	92722656	92722808
ENSE00000869914	92720300	92720755
ENSE00000869915	92718539	92719582
ENSE00000869916	92717797	92717948
ENSE00001404188	92711363	92715463
ENSE00003844327	92764505	92764833

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.4067 / max 297.4962, expressed in 1665 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101451	5.4067	1665

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	98.68	gold quality
gingiva	UBERON:0001828	98.63	gold quality
hair follicle	UBERON:0002073	98.58	gold quality
cervix squamous epithelium	UBERON:0006922	98.39	gold quality
penis	UBERON:0000989	97.92	gold quality
tongue squamous epithelium	UBERON:0006919	97.54	gold quality
nipple	UBERON:0002030	97.01	gold quality
mammalian vulva	UBERON:0000997	96.86	gold quality
upper arm skin	UBERON:0004263	96.70	gold quality
oral cavity	UBERON:0000167	96.67	gold quality
upper leg skin	UBERON:0004262	96.18	gold quality
squamous epithelium	UBERON:0006914	96.18	gold quality
skin of hip	UBERON:0001554	95.80	gold quality
cervix epithelium	UBERON:0004801	95.48	gold quality
pharyngeal mucosa	UBERON:0000355	95.41	gold quality
amniotic fluid	UBERON:0000173	94.71	gold quality
saphenous vein	UBERON:0007318	94.52	gold quality
zone of skin	UBERON:0000014	94.43	gold quality
superior surface of tongue	UBERON:0007371	94.33	gold quality
esophagus squamous epithelium	UBERON:0006920	94.32	gold quality
epithelium of esophagus	UBERON:0001976	94.27	gold quality
tongue	UBERON:0001723	94.21	gold quality
skin of abdomen	UBERON:0001416	93.97	gold quality
skin of leg	UBERON:0001511	93.83	gold quality
body of tongue	UBERON:0011876	93.72	gold quality
seminal vesicle	UBERON:0000998	93.54	gold quality
palpebral conjunctiva	UBERON:0001812	93.06	gold quality
superficial temporal artery	UBERON:0001614	92.64	gold quality
germinal epithelium of ovary	UBERON:0001304	92.54	gold quality
esophagus mucosa	UBERON:0002469	92.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

185 targeting BICD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6835-3P	99.93	70.49	2904

Literature-anchored findings (GeneRIF, showing 32)

• isolation, cloning, and characterization of human Nek8, a new mammalian NIMA-related kinase, and its candidate substrate Bicd2 (PMID:11864968)
• Data suggest that ASUN promotes perinuclear enrichment of dynein at G2/M that facilitates BICD2- and CENP-F-mediated anchoring of dynein to nuclear pore complexes. (PMID:23097494)
• Mutations in BICD2 cause congenital autosomal-dominant spinal muscular atrophy and massive Golgi fragmentation in affected cells. (PMID:23664116)
• BICD2 mutations cause non-5q linked spinal muscular atrophy in humans (PMID:23664119)
• Disease causing mutations resulting in amino acid substitutions in two binding regions of BICD2 increase its binding affinity for the cytoplasmic dynein-dynactin complex. (PMID:23664120)
• This study identified BICD3 significantly associated loci with a biologically plausible role in schizophrenia. (PMID:24507884)
• the features of BICD2 spinal muscular atrophy, lower extremity predominant are consistent with a pathological process that preferentially affects lumbar lower motor neurons (PMID:25497877)
• several analyses of vesicular transport demonstrated that Rab6A and BICD2 play crucial roles in Golgi tubule fusion with the endoplasmic reticulum (ER) in brefeldin A (BFA)-treated cells (PMID:25962623)
• These findings give further insight into the clinical and pathoanatomical consequences of BICD2 mutations. (PMID:26998597)
• Data suggest that BICD1 and BICD2 are highly expressed in the nervous system during development and are important in neuronal homeostasis. [REVIEW] (PMID:28215293)
• BICD2 missense mutations were identified in patients with severe muscular atrophy with arthrogryposis and asymptomatic individuals with subclinical features. (PMID:28635954)
• results reveal that dominant mutations in BICD2 hyperactivate DDB motility and suggest that an imbalance of minus versus plus end-directed microtubule motility in neurons may underlie spinal muscular atrophy. (PMID:28883039)
• BICD2 facilitates infection by promoting the trafficking of viral cores to the nucleus, thereby promoting nuclear entry of the viral genome and infection (PMID:29180435)
• A family with three members affected by spinal muscular dystrophy 2, caused by the first in-frame deletion of BICD2 is described. (PMID:29353221)
• our findings contribute to the better understanding of spinal muscular atrophy-2 pathology by providing evidence for a common pathomechanism of BICD2 mutations that increase microtubule stability in motor neurons leading to increased axonal branching and to impaired neuromuscular junction development. (PMID:29528393)
• Results provide evidence that BICD2 is a capsid-associated dynein adaptor utilized by HIV-1 for transport to the nucleus. (PMID:30068656)
• BICD2 mutations appear rather unlikely to cause a phenotype of hereditary motor and sensory neuropathy and are a very rare cause of the hereditary spastic paraplegia phenotype (PMID:30536747)
• A novel heterozygous mutation in the BICD2 gene that led to substitution of valine for leucine at residue 121 of BICD2 (p.L121V) was identified in an autosomal dominant inherited family. (PMID:30738493)
• Hypoxia-induced changes in intragenic DNA methylation correlate with alternative splicing in breast cancer. (PMID:31965981)
• Clinical spectrum of BICD2 mutations. (PMID:32056343)
• In this review, we identify the characteristics of disease-causing variants in BICD2 that distinguish them from benign variation and perform genotype-phenotype correlations for 99 BICD2 variant carriers from 35 families. [Review] (PMID:32057122)
• Loss of BICD2 in muscle drives motor neuron loss in a developmental form of spinal muscular atrophy. (PMID:32183910)
• Impairment in dynein-mediated nuclear translocation by BICD2 C-terminal truncation leads to neuronal migration defect and human brain malformation. (PMID:32665036)
• circBICD2 targets miR-149-5p/IGF2BP1 axis to regulate oral squamous cell carcinoma progression. (PMID:33382158)
• Fetal early motor neuron disruption and prenatal molecular diagnosis in a severe BICD2-opathy. (PMID:33547725)
• Elevated BICD2 DNA methylation in blood of major depressive disorder patients and reduction of depressive-like behaviors in hippocampal Bicd2-knockdown mice. (PMID:35858435)
• Identification and functional characterization of BICD2 as a candidate disease gene in an consanguineous family with dilated cardiomyopathy. (PMID:36068540)
• In vitro characterization of the full-length human dynein-1 cargo adaptor BicD2. (PMID:36150379)
• Role of Nesprin-2 and RanBP2 in BICD2-associated brain developmental disorders. (PMID:36930595)
• Microscopic and Biochemical Hallmarks of BICD2-Associated Muscle Pathology toward the Evaluation of Novel Variants. (PMID:37047781)
• m6Am methyltransferase PCIF1 negatively regulates ciliation by inhibiting BICD2 expression. (PMID:38526325)
• Molecular mechanism for recognition of the cargo adapter Rab6[GTP] by the dynein adapter BicD2. (PMID:38719748)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	BICD2	ENSDARG00000098215
mus_musculus	Bicd2	ENSMUSG00000037933
rattus_norvegicus	Bicd2	ENSRNOG00000016031
drosophila_melanogaster	BicD	FBGN0000183
caenorhabditis_elegans		WBGENE00016611

Paralogs (1): BICD1 (ENSG00000151746)

Protein

Protein identifiers

Protein bicaudal D homolog 2 — Q8TD16 (reviewed: Q8TD16)

All UniProt accessions (1): Q8TD16

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates and stabilizes the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Facilitates the binding of RAB6A to the Golgi by stabilizing its GTP-bound form. Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport via its interaction with RAB6A and recruitment of the dynein-dynactin motor complex. Contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1. During G2 phase of the cell cycle, associates with RANBP2 at the nuclear pores and recruits dynein and dynactin to the nuclear envelope to ensure proper positioning of the nucleus relative to centrosomes prior to the onset of mitosis.

Subunit / interactions. Part of a tripartite complex with dynein and dynactin, acts an adapter linking the dynein motor complex and dynactin. Interacts with CPNE4 (via VWFA domain). Interacts with RAB6A. Interacts with NEK9. Interacts with DNAI1. Interacts with DYNC1H1. Interacts with RANBP2. Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules. Interacts with DYNLL1, DYNC1I2; DCTN1, DCTN2 and KIF5A. Interacts with KIF1C.

Subcellular location. Golgi apparatus. Cytoplasm. Cytoskeleton. Nucleus envelope. Nucleus. Nuclear pore complex.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by NEK9 in vitro.

Disease relevance. Spinal muscular atrophy, lower extremity-predominant 2A, childhood onset, autosomal dominant (SMALED2A) [MIM:615290] An autosomal dominant form of spinal muscular atrophy characterized by early-childhood onset of muscle weakness and atrophy predominantly affecting the proximal and distal muscles of the lower extremity, although some patients may show upper extremity involvement. The disorder results in delayed walking, waddling gait, difficulty walking, and loss of distal reflexes. Some patients may have foot deformities or hyperlordosis, and some show mild upper motor signs, such as spasticity. Sensation, bulbar function, and cognitive function are preserved. The disorder shows very slow progression throughout life. The disease is caused by variants affecting the gene represented in this entry. Spinal muscular atrophy, lower extremity-predominant, 2B, prenatal onset, autosomal dominant (SMALED2B) [MIM:618291] An autosomal dominant neuromuscular disorder characterized by decreased fetal movements, fractures in utero, severe congenital joint contractures, arthrogryposis multiplex congenita, severe hypotonia, muscle atrophy, and respiratory insufficiency and failure due to muscle weakness. Some patients may have dysmorphic facial features and/or abnormalities on brain imaging. Death in early childhood may occur. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The fourth coiled coil region is involved in Golgi targeting and in the interaction with DCTN2.

Miscellaneous. Due to intron retention.

Similarity. Belongs to the BicD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TD16-1	1	yes
Q8TD16-2	2

RefSeq proteins (2): NP_001003800, NP_056065 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018477	BICD	Family

Pfam: PF09730

UniProt features (45 total): modified residue 13, sequence variant 12, region of interest 8, helix 4, coiled-coil region 3, compositionally biased region 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6OFP	X-RAY DIFFRACTION	2.01
6PSE	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD16-F1	78.89	0.51

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (13): 2, 190, 224, 318, 319, 343, 395, 568, 574, 582, 602, 821, 823

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6811436	COPI-independent Golgi-to-ER retrograde traffic
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
R-HSA-8856688	Golgi-to-ER retrograde transport

MSigDB gene sets: 463 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_MICROTUBULE_ANCHORING, JAEGER_METASTASIS_DN, TGCACTT_MIR519C_MIR519B_MIR519A, TATTATA_MIR374, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOMF_GTPASE_BINDING, GOCC_MICROTUBULE_ORGANIZING_CENTER, AGGCACT_MIR5153P, GTGCCTT_MIR506, RICKMAN_METASTASIS_DN

GO Biological Process (9): retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), microtubule-based movement (GO:0007018), protein transport (GO:0015031), protein localization to Golgi apparatus (GO:0034067), mRNA transport (GO:0051028), centrosome localization (GO:0051642), regulation of microtubule cytoskeleton organization (GO:0070507), minus-end-directed organelle transport along microtubule (GO:0072385), microtubule anchoring at microtubule organizing center (GO:0072393)

GO Molecular Function (6): cytoskeletal adaptor activity (GO:0008093), small GTPase binding (GO:0031267), dynactin binding (GO:0034452), dynein light intermediate chain binding (GO:0051959), dynein complex binding (GO:0070840), protein binding (GO:0005515)

GO Cellular Component (11): nuclear envelope (GO:0005635), annulate lamellae (GO:0005642), nuclear pore (GO:0005643), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), nucleus (GO:0005634), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Golgi-to-ER retrograde transport	1
Vesicle-mediated transport	1
Membrane Trafficking	1
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cytoskeletal protein binding	2
endomembrane system	2
membrane	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
Golgi vesicle transport	1
microtubule-based process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein localization to organelle	1
RNA transport	1
microtubule organizing center localization	1
microtubule cytoskeleton organization	1
regulation of microtubule-based process	1
regulation of cytoskeleton organization	1
organelle transport along microtubule	1
microtubule anchoring	1
protein-macromolecule adaptor activity	1
GTPase binding	1
protein binding	1
protein-containing complex binding	1
binding	1
nucleus	1
organelle envelope	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
nuclear envelope	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cell periphery	1
intracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1582 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BICD2	RANBP2	P49792	993
BICD2	RAB6A	P20340	944
BICD2	RGPD1	P0C839	895
BICD2	NEK9	Q8TD19	875
BICD2	DCTN2	Q13561	852
BICD2	HOOK3	Q86VS8	842
BICD2	BICDL1	Q6ZP65	831
BICD2	DYNC1LI1	Q9Y6G9	789
BICD2	NEK6	Q9HC98	776
BICD2	NEK7	Q8TDX7	762
BICD2	RAB11FIP3	O75154	731
BICD2	DYNC1H1	Q14204	723
BICD2	HOOK1	Q9UJC3	704
BICD2	KIF5B	P33176	679
BICD2	CSN2	P05814	673

IntAct

97 interactions, top by confidence:

A	B	Type	Score
PLK1	SPAG9	psi-mi:“MI:0914”(association)	0.790
MIS18A	DCTN6	psi-mi:“MI:0914”(association)	0.640
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
ORF	EIF3D	psi-mi:“MI:0914”(association)	0.560
CAPN6	UBA6	psi-mi:“MI:0914”(association)	0.530
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
ORC6	DCTN6	psi-mi:“MI:0914”(association)	0.530
COG6	EXOC5	psi-mi:“MI:0914”(association)	0.530
CPNE5	RAD21	psi-mi:“MI:0914”(association)	0.530
NEFL	RABEP1	psi-mi:“MI:0914”(association)	0.530
PLK1	PPP6C	psi-mi:“MI:0914”(association)	0.530
KXD1	TRAK2	psi-mi:“MI:0914”(association)	0.530
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
DYNC1I1	BICD2	psi-mi:“MI:0915”(physical association)	0.520
BICD2	DYNC1I1	psi-mi:“MI:0915”(physical association)	0.520
BICD2	RAB6A	psi-mi:“MI:0915”(physical association)	0.460
BICD2	RAB6A	psi-mi:“MI:0403”(colocalization)	0.460
RANBP2	BICD2	psi-mi:“MI:0915”(physical association)	0.400
BICD2	H1-5	psi-mi:“MI:0915”(physical association)	0.400
NEK9	BICD2	psi-mi:“MI:0915”(physical association)	0.400
H1-2	BICD2	psi-mi:“MI:0915”(physical association)	0.400
ACTR1A	BICD2	psi-mi:“MI:0915”(physical association)	0.400
H1-4	BICD2	psi-mi:“MI:0915”(physical association)	0.400
MFAP1	BICD2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (596): BICD2 (Affinity Capture-MS), BICD2 (Two-hybrid), RAB6A (Two-hybrid), BICD2 (Affinity Capture-MS), BICD2 (Affinity Capture-MS), BICD2 (Affinity Capture-MS), BICD2 (Affinity Capture-MS), BICD2 (Biochemical Activity), NEK9 (Affinity Capture-Western), BICD2 (Affinity Capture-Western), BICD2 (Affinity Capture-MS), BICD2 (Affinity Capture-Western), BICD2 (Proximity Label-MS), BICD2 (Proximity Label-MS), BICD2 (Affinity Capture-MS)

ESM2 similar proteins: A0PJP4, A0PJT0, A2VDP1, D3ZUQ0, O60271, O75150, P46825, Q0IHE5, Q0P485, Q0V989, Q14BN4, Q17QG3, Q28623, Q2QLI6, Q3U319, Q4R7K7, Q4V872, Q58A65, Q5DTM8, Q5EBL4, Q5R5R4, Q5RAU7, Q5VTR2, Q5ZLS3, Q653N3, Q68CZ1, Q6DFC2, Q6GQ73, Q6IMY1, Q7Z3E2, Q86VS8, Q8BR07, Q8BUK6, Q8C9S4, Q8CG73, Q8CJB9, Q8IYE1, Q8L7S4, Q8R4C2, Q8TD16

Diamond homologs: P16568, Q8BR07, Q8TD16, Q921C5, Q96G01, V6CJ04

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RANBP2	“up-regulates quantity”	BICD2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPI-independent Golgi-to-ER retrograde traffic	7	18.9×	6e-06
Aggrephagy	5	16.1×	3e-04
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	15.1×	7e-05
Loss of Nlp from mitotic centrosomes	7	14.4×	2e-05
Loss of proteins required for interphase microtubule organization from the centrosome	7	14.4×	2e-05
AURKA Activation by TPX2	7	13.8×	2e-05
EML4 and NUDC in mitotic spindle formation	11	13.3×	1e-07
Resolution of Sister Chromatid Cohesion	11	12.4×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
microtubule bundle formation	5	25.3×	3e-04
mitotic spindle organization	5	13.5×	3e-03
nucleosome assembly	8	11.1×	3e-04
cell division	11	5.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

963 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	20
Uncertain significance	417
Likely benign	367
Benign	35

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1707086	NM_001003800.2(BICD2):c.2100C>G (p.Asn700Lys)	Pathogenic
2579842	NM_001003800.2(BICD2):c.2113G>A (p.Glu705Lys)	Pathogenic
2865170	NM_001003800.2(BICD2):c.1922T>A (p.Leu641Gln)	Pathogenic
3233668	NM_001003800.2(BICD2):c.2100C>A (p.Asn700Lys)	Pathogenic
3342840	NM_001003800.2(BICD2):c.593T>C (p.Leu198Pro)	Pathogenic
3775573	NM_001003800.2(BICD2):c.342C>G (p.Tyr114Ter)	Pathogenic
419443	NM_001003800.2(BICD2):c.2231C>T (p.Ser744Phe)	Pathogenic
55857	NM_001003800.2(BICD2):c.320C>T (p.Ser107Leu)	Pathogenic
55860	NM_001003800.2(BICD2):c.2321A>G (p.Glu774Gly)	Pathogenic
617527	NM_001003800.2(BICD2):c.581A>G (p.Gln194Arg)	Pathogenic
637066	NM_001003800.2(BICD2):c.1604C>T (p.Ala535Val)	Pathogenic
862389	NM_001003800.2(BICD2):c.1667A>G (p.Tyr556Cys)	Pathogenic
989145	NM_001003800.2(BICD2):c.1519AAG[1] (p.Lys508del)	Pathogenic
1018827	NM_001003800.2(BICD2):c.2058G>T (p.Lys686Asn)	Likely pathogenic
1335730	NM_001003800.2(BICD2):c.560A>G (p.Glu187Gly)	Likely pathogenic
1375587	NM_001003800.2(BICD2):c.567C>G (p.Ile189Met)	Likely pathogenic
1527969	NM_001003800.2(BICD2):c.1543G>A (p.Glu515Lys)	Likely pathogenic
208737	NM_001003800.2(BICD2):c.1589T>C (p.Phe530Ser)	Likely pathogenic
2431200	NM_001003800.2(BICD2):c.2200A>G (p.Lys734Glu)	Likely pathogenic
2441951	NM_001003800.2(BICD2):c.538G>A (p.Asp180Asn)	Likely pathogenic
2442262	NM_001003800.2(BICD2):c.1922T>G (p.Leu641Arg)	Likely pathogenic
2444193	NM_001003800.2(BICD2):c.629A>C (p.His210Pro)	Likely pathogenic
3064531	NM_001003800.2(BICD2):c.535C>T (p.Gln179Ter)	Likely pathogenic
3773706	NM_001003800.2(BICD2):c.570C>A (p.Ser190Arg)	Likely pathogenic
422412	NM_001003800.2(BICD2):c.1646C>T (p.Pro549Leu)	Likely pathogenic
4813696	NM_001003800.2(BICD2):c.2056A>G (p.Lys686Glu)	Likely pathogenic
637065	NM_001003800.2(BICD2):c.565A>T (p.Ile189Phe)	Likely pathogenic
647320	NM_001003800.2(BICD2):c.1667A>C (p.Tyr556Ser)	Likely pathogenic
648279	NM_001003800.2(BICD2):c.2105A>G (p.Gln702Arg)	Likely pathogenic
650473	NM_001003800.2(BICD2):c.1633A>G (p.Asn545Asp)	Likely pathogenic

SpliceAI

1835 predictions. Top by Δscore:

Variant	Effect	Δscore
9:92715251:A:AC	donor_gain	1.0000
9:92715251:ACG:A	donor_gain	1.0000
9:92715251:ACGCT:A	donor_gain	1.0000
9:92715252:C:CC	donor_gain	1.0000
9:92715252:CG:C	donor_gain	1.0000
9:92715252:CGC:C	donor_gain	1.0000
9:92715252:CGCT:C	donor_gain	1.0000
9:92715252:CGCTC:C	donor_gain	1.0000
9:92715460:ACAC:A	acceptor_gain	1.0000
9:92715461:CAC:C	acceptor_gain	1.0000
9:92715461:CACC:C	acceptor_gain	1.0000
9:92715462:AC:A	acceptor_gain	1.0000
9:92715462:ACCTG:A	acceptor_loss	1.0000
9:92715463:CC:C	acceptor_gain	1.0000
9:92715464:C:CC	acceptor_gain	1.0000
9:92717792:GTTA:G	donor_loss	1.0000
9:92717793:TTAC:T	donor_loss	1.0000
9:92717794:TA:T	donor_loss	1.0000
9:92717795:A:AG	donor_loss	1.0000
9:92717796:C:CT	donor_loss	1.0000
9:92717842:T:TA	donor_gain	1.0000
9:92717945:CCGT:C	acceptor_gain	1.0000
9:92717946:CGTC:C	acceptor_gain	1.0000
9:92717957:CAGA:C	acceptor_gain	1.0000
9:92717960:A:AC	acceptor_gain	1.0000
9:92717960:A:C	acceptor_gain	1.0000
9:92717962:G:C	acceptor_gain	1.0000
9:92717962:G:GC	acceptor_gain	1.0000
9:92717964:G:C	acceptor_gain	1.0000
9:92717964:G:GC	acceptor_gain	1.0000

AlphaMissense

5577 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:92715377:A:G	L782P	1.000
9:92717805:A:C	F750L	1.000
9:92717805:A:T	F750L	1.000
9:92717807:A:G	F750L	1.000
9:92717826:G:C	F743L	1.000
9:92717826:G:T	F743L	1.000
9:92717828:A:G	F743L	1.000
9:92717857:A:G	L733P	1.000
9:92717866:C:G	R730P	1.000
9:92717869:A:G	L729P	1.000
9:92717923:A:G	L711P	1.000
9:92717945:C:G	A704P	1.000
9:92718542:C:A	K701N	1.000
9:92718542:C:G	K701N	1.000
9:92718550:C:G	A699P	1.000
9:92718555:A:G	L697P	1.000
9:92718555:A:T	L697H	1.000
9:92718564:C:G	R694P	1.000
9:92718565:G:T	R694S	1.000
9:92718567:A:G	L693P	1.000
9:92718579:T:G	Q689P	1.000
9:92718585:C:G	R687P	1.000
9:92718723:A:G	L641P	1.000
9:92719035:A:G	L537P	1.000
9:92719044:A:G	L534P	1.000
9:92719065:A:G	L527P	1.000
9:92764615:C:G	A44P	1.000
9:92764618:C:G	A43P	1.000
9:92715347:A:G	L792P	0.999
9:92715353:A:G	L790P	0.999

dbSNP variants (sampled 300 via entrez): RS1000023659 (9:92759843 A>G), RS1000061876 (9:92725057 A>G), RS1000095269 (9:92760296 C>A,T), RS1000145463 (9:92717670 G>A,T), RS1000162516 (9:92735997 A>G), RS1000268138 (9:92754245 T>C), RS1000382855 (9:92748036 G>T), RS1000536245 (9:92765096 G>A), RS1000592538 (9:92743356 T>A,C), RS1000645729 (9:92749591 T>C,G), RS1000664335 (9:92723663 A>C,G), RS1000673701 (9:92742163 G>A), RS1000714007 (9:92749373 G>C), RS1000791138 (9:92749506 C>T), RS1000796053 (9:92725745 G>A)

Disease associations

OMIM: gene MIM:609797 | disease phenotypes: MIM:615290, MIM:618291, MIM:158600, MIM:118220, MIM:182960, MIM:303350, MIM:617468, MIM:614751, MIM:253300, MIM:160500, MIM:182600, MIM:616878

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	Definitive	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant
spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant	Strong	Autosomal recessive

Mondo (18): autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (MONDO:0014121), spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant (MONDO:0032660), autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures (MONDO:0008026), Charcot-Marie-Tooth disease (MONDO:0015626), neuronopathy, distal hereditary motor, autosomal dominant (MONDO:0015362), hereditary spastic paraplegia (MONDO:0019064), autism spectrum disorder (MONDO:0005258), autosomal dominant childhood-onset proximal spinal muscular atrophy (MONDO:0018190), amyotrophic lateral sclerosis (MONDO:0004976), muscular atrophy (MONDO:0004323), arthrogryposis multiplex congenita (MONDO:0015168), neuronopathy, distal hereditary motor, type 5B (MONDO:0013884), spinal muscular atrophy (MONDO:0001516), distal myopathy (MONDO:0018949), hereditary spastic paraplegia 3A (MONDO:0008437)

Orphanet (14): Autosomal dominant childhood-onset proximal spinal muscular atrophy (Orphanet:363447), BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy (Orphanet:363454), DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy (Orphanet:209341), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Autosomal dominant hereditary axonal motor and sensory neuropathy (Orphanet:140456), Autosomal dominant distal hereditary motor neuropathy (Orphanet:140465), Hereditary spastic paraplegia (Orphanet:685), Amyotrophic lateral sclerosis (Orphanet:803), Arthrogryposis multiplex congenita (Orphanet:1037), Distal hereditary motor neuropathy type 5 (Orphanet:139536), Distal myopathy (Orphanet:599), Autosomal dominant spastic paraplegia type 3 (Orphanet:100984), Recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (Orphanet:480864), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

89 total (30 of 89 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000256	Macrocephaly
HP:0000347	Micrognathia
HP:0000377	Abnormal pinna morphology
HP:0000767	Pectus excavatum
HP:0000954	Single transverse palmar crease
HP:0000960	Sacral dimple
HP:0001181	Adducted thumb
HP:0001188	Hand clenching
HP:0001249	Intellectual disability
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001283	Bulbar palsy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001374	Congenital hip dislocation
HP:0001385	Hip dysplasia
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001763	Pes planus
HP:0001771	Achilles tendon contracture
HP:0002061	Lower limb spasticity
HP:0002079	Hypoplasia of the corpus callosum
HP:0002091	Restrictive ventilatory defect

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001524_22	Visceral adipose tissue/subcutaneous adipose tissue ratio	2.000000e-06
GCST008839_217	Height	6.000000e-11
GCST010725_16	Malaria	9.000000e-06
GCST010725_28	Malaria	6.000000e-06
GCST010725_95	Malaria	6.000000e-06
GCST90000025_474	Appendicular lean mass	2.000000e-22
GCST90002398_155	Neutrophil count	3.000000e-09
GCST90002402_66	Platelet count	1.000000e-12
GCST90002407_117	White blood cell count	6.000000e-12
GCST90014033_92	Haemorrhoidal disease	3.000000e-08
GCST90020025_1131	Waist-to-hip ratio adjusted for BMI	4.000000e-08
GCST90020027_914	Waist-hip index	4.000000e-08
GCST90020028_344	Hip circumference adjusted for BMI	6.000000e-11
GCST90020028_345	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004980	appendicular lean mass
EFO:0004833	neutrophil count
EFO:0004309	platelet count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D009133	Muscular Atrophy	C10.597.613.612; C23.300.070.500; C23.888.592.608.612
D009134	Muscular Atrophy, Spinal	C10.228.854.468; C10.574.562.500; C10.668.467.500
D065886	Neurodevelopmental Disorders	F03.625
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C536864	Spastic paraplegia 3, autosomal dominant (supp.)
C563560	Spinal Muscular Atrophy, Childhood, Proximal, Autosomal Dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
Cadmium Chloride	decreases expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
epigallocatechin gallate	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
clothianidin	decreases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Calcium Chloride	increases expression	1
Estradiol	affects expression	1
Ivermectin	decreases expression	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	decreases expression	1
Cyclosporine	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C3R2	CRICKi007-A	Induced pluripotent stem cell	Female
CVCL_D9YL	Ubigene HeLa BICD2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

497 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder