SMG1

SMG1 nonsense mediated mRNA decay associated PI3K related kinase, the group of SMG1 complex|DECID complex|Armadillo like helical domain containing

Basic information

Region (hg38): 16:18804860-18926408

Links

ENSG00000157106 ∙ NCBI:23049 ∙ OMIM:607032 ∙ HGNC:30045 ∙ Uniprot:Q96Q15 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMG1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	5	2	8
missense			23	1	3	27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	24	6	5

Variants in SMG1

This is a list of pathogenic ClinVar variants found in the SMG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-18812121-C-T		not specified	Uncertain significance (Aug 10, 2021)
16-18816363-A-G		not specified	Uncertain significance (Jul 28, 2021)
16-18817390-C-T			Likely benign (Nov 01, 2022)
16-18819585-A-G			Likely benign (Jan 01, 2023)
16-18829459-G-A		not specified	Uncertain significance (Aug 17, 2021)
16-18829977-T-C		not specified	Uncertain significance (Jul 06, 2021)
16-18834273-T-C			Likely benign (Aug 14, 2018)
16-18835939-T-C		not specified	Uncertain significance (Oct 29, 2021)
16-18836186-C-T		not specified	Uncertain significance (Sep 17, 2021)
16-18837383-A-G			Uncertain significance (Apr 01, 2022)
16-18838114-T-C		not specified	Uncertain significance (Oct 06, 2021)
16-18848040-T-A			Likely benign (Mar 01, 2018)
16-18850274-C-T		not specified	Uncertain significance (Aug 09, 2021)
16-18853610-A-C		not specified	Uncertain significance (Sep 01, 2021)
16-18853684-G-A		not specified	Uncertain significance (Aug 13, 2021)
16-18859071-T-A		not specified	Uncertain significance (Aug 02, 2021)
16-18859589-A-G		not specified	Uncertain significance (Jul 14, 2021)
16-18863720-C-A			Benign (Aug 14, 2018)
16-18863836-G-C		not specified	Uncertain significance (Sep 14, 2021)
16-18864053-T-A		not specified	Uncertain significance (Sep 15, 2021)
16-18866676-T-C		not specified	Likely benign (Aug 13, 2021)
16-18866729-C-T		not specified	Uncertain significance (Nov 15, 2021)
16-18869141-T-C			Benign (Mar 01, 2018)
16-18869926-C-T		not specified	Uncertain significance (Jul 13, 2021)
16-18871408-G-C		not specified	Uncertain significance (Aug 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMG1	protein_coding	protein_coding	ENST00000446231	63	121602

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.30e-25	124651	0	6	124657	0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.30	1372	1.76e+3	0.779	0.0000937	23799
Missense in Polyphen		424	736.79	0.57547		10252
Synonymous	-2.76	736	647	1.14	0.0000357	7024
Loss of Function	11.9	4	172	0.0232	0.00000908	2272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.0000355	0.0000354
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. {ECO:0000269|PubMed:11331269, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:15175154, ECO:0000269|PubMed:16452507}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);Metabolism of RNA;Nonsense-Mediated Decay (NMD);Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (Consensus)

Intolerance Scores

• rvis_EVS: -2.98
• rvis_percentile_EVS: 0.54

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.760
• ghis: 0.628

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.818

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Smg1
• Phenotype: craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; neoplasm

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;DNA repair;mRNA export from nucleus;peptidyl-serine phosphorylation;regulation of telomere maintenance;protein autophosphorylation;phosphatidylinositol phosphorylation;regulation of response to DNA damage stimulus
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: RNA binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;telomeric DNA binding;metal ion binding