SMN1 (survival of motor neuron 1, telomeric; HGNC:11117, NCBI Gene ID 6606) is a human locus mapped to chromosome band 5q13.2 that encodes survival motor neuron protein SMN (294 aa). SMN1 acts in spliceosomal U-rich snRNP biogenesis & alpha-motor neuron axonal RNA transport, together with SMN2 (Centromeric Backup Gene), Small Nuclear RNA (snRNA), and Antisense Oligonucleotides (ASOs). Encodes the survival motor neuron protein required for snRNP assembly; biallelic loss causes spinal muscular atrophy.
Approved Symbol
SMN1
Chromosomal Locus
5q13.2
Encoded Product
Survival motor neuron protein SMN (294 aa)
Primary Pathway
Spliceosomal U-rich snRNP biogenesis & alpha-motor neuron axonal RNA transport
Genomic Organization & Cytogenetic Locus: 9-exon telomeric gene (exons 1, 2a, 2b, 3–8) located within an inverted 500 kb segmental duplication on chromosome 5q13.2 alongside its nearly identical centromeric paralog SMN2, differing at five nucleotides including a critical C nucleotide at position +6 of exon 7 that ensures full-length exon 7 inclusion.
Cellular & Tissue Expression Profile: Ubiquitously expressed in all somatic cells inside nuclear Cajal bodies (gems) and cytoplasm, with spinal cord alpha-motor neurons exhibiting extreme vulnerability to reduced SMN protein levels.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Forms the core of the macromolecular SMN-Gemin2-8 complex, which chaperones the ATP-dependent assembly of the heptameric Sm protein ring onto spliceosomal small nuclear RNAs (U1, U2, U4, U5, U11, U12 snRNAs) and mediates axonal mRNP transport to neuromuscular junctions.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Homozygous deletion or gene conversion of SMN1 exon 7 accounts for approximately 95% of autosomal recessive 5q spinal muscular atrophy (SMA types 1–4), previously the leading monogenic cause of infant mortality prior to molecular therapies.
Therapeutic & Clinical Pharmacology: Directly replaced in spinal motor neurons by intravenous self-complementary AAV9 gene therapy onasemnogene abeparvovec (Zolgensma), while complementary therapeutics nusinersen (ASO) and risdiplam (small molecule) up-regulate full-length SMN protein from the backup SMN2 paralog.