Spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant

Summary

Spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant (MONDO:0032660) is a disease caused by BICD2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BICD2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant
Mondo ID	MONDO:0032660
OMIM	618291
DOID	DOID:0070350
UMLS	C4749003
MedGen	1648362
GARD	0025715
Is cancer (heuristic)	no

Also known as: SMALED2B · spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant

Data availability: 17 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › spinal muscular atrophy › proximal spinal muscular atrophy › autosomal dominant childhood-onset proximal spinal muscular atrophy › spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant

Related subtypes (2): autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures, autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

17 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 4 pathogenic/likely pathogenic, 3 likely pathogenic, 2 benign/likely benign, 1 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323979	NM_001003800.2(BICD2):c.2081G>A (p.Arg694His)	BICD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210526	NM_001003800.2(BICD2):c.2080C>T (p.Arg694Cys)	BICD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
422408	NM_001003800.2(BICD2):c.1636_1638del (p.Asn546del)	BICD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
429371	NM_001003800.2(BICD2):c.2320G>A (p.Glu774Lys)	BICD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
617527	NM_001003800.2(BICD2):c.581A>G (p.Gln194Arg)	BICD2	Pathogenic	no assertion criteria provided
1527969	NM_001003800.2(BICD2):c.1543G>A (p.Glu515Lys)	BICD2	Likely pathogenic	criteria provided, single submitter
2441951	NM_001003800.2(BICD2):c.538G>A (p.Asp180Asn)	BICD2	Likely pathogenic	criteria provided, single submitter
4813696	NM_001003800.2(BICD2):c.2056A>G (p.Lys686Glu)	BICD2	Likely pathogenic	criteria provided, single submitter
1504892	NM_001003800.2(BICD2):c.902A>G (p.Asn301Ser)	BICD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1773727	NM_001003800.2(BICD2):c.1489_1491delinsTCA (p.Glu497Ser)	BICD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431908	NM_001003800.2(BICD2):c.1579C>G (p.Leu527Val)	BICD2	Uncertain significance	criteria provided, single submitter
3381915	NM_001003800.2(BICD2):c.361C>G (p.Leu121Val)	BICD2	Uncertain significance	criteria provided, single submitter
3612987	NM_001003800.2(BICD2):c.1853G>A (p.Ser618Asn)	BICD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
834774	NM_001003800.2(BICD2):c.871G>A (p.Glu291Lys)	BICD2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1167684	NM_001003800.2(BICD2):c.1401C>T (p.His467=)	BICD2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
387003	NM_001003800.2(BICD2):c.2258+15G>C	BICD2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
678244	NM_001003800.2(BICD2):c.1063-111G>C	BICD2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BICD2	Definitive	Autosomal dominant	autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BICD2	Orphanet:363454	BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BICD2	HGNC:17208	ENSG00000185963	Q8TD16	Protein bicaudal D homolog 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BICD2	Protein bicaudal D homolog 2	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BICD2	Other/Unknown	no		BICD

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	1
gingival epithelium	1
hair follicle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BICD2	290	ubiquitous	marker	gingival epithelium, gingiva, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BICD2	2,275

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BICD2	Q8TD16	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.016	BICD2
Golgi-to-ER retrograde transport	1	132.8×	0.016	BICD2
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.016	BICD2
Membrane Trafficking	1	37.1×	0.029	BICD2
Vesicle-mediated transport	1	34.8×	0.029	BICD2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
microtubule anchoring at microtubule organizing center	1	8426.0×	0.001	BICD2
minus-end-directed organelle transport along microtubule	1	4213.0×	0.001	BICD2
centrosome localization	1	887.0×	0.003	BICD2
protein localization to Golgi apparatus	1	802.5×	0.003	BICD2
regulation of microtubule cytoskeleton organization	1	543.6×	0.003	BICD2
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	337.0×	0.004	BICD2
microtubule-based movement	1	295.6×	0.004	BICD2
mRNA transport	1	263.3×	0.004	BICD2
protein transport	1	43.9×	0.023	BICD2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BICD2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BICD2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BICD2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.