SMN1

Highest pathogenic variant AF is 0.0007965045

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000380707

Coding exons

8

Length

29002

Individuals with no LoFs

124181

Homozygous LoFs

0

Heterozygous LoFs

5

Defined

124186

p

0.0000201

Function

FUNCTION: The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs). {ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:23063131, ECO:0000269|PubMed:26700805, ECO:0000269|PubMed:9845364}.;

Disease

DISEASE: Spinal muscular atrophy 1 (SMA1) [MIM:253300]: A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7- skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:15249625, ECO:0000269|PubMed:15580564, ECO:0000269|PubMed:7813012, ECO:0000269|PubMed:9147655}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy 2 (SMA2) [MIM:253550]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. It has intermediate severity, with onset between 6 and 18 months. Patients do not reach the motor milestone of standing, and survive into adulthood. {ECO:0000269|PubMed:10732802, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy 3 (SMA3) [MIM:253400]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is after 18 months. Patients develop ability to stand and walk and survive into adulthood. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:9158159, ECO:0000269|PubMed:9837824}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinal muscular atrophy 4 (SMA4) [MIM:271150]: An autosomal recessive form of spinal muscular atrophy, a neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Onset is in adulthood, disease progression is slow, and patients can stand and walk. {ECO:0000269|PubMed:7658877, ECO:0000269|PubMed:8551862}. Note=The disease is caused by mutations affecting the gene represented in this entry.;