SMG8

SMG8 nonsense mediated mRNA decay factor, the group of SMG1 complex

Basic information

Region (hg38): 17:59209400-59215239

Previous symbols: [ "C17orf71" ]

Links

ENSG00000167447 ∙ NCBI:55181 ∙ OMIM:613175 ∙ HGNC:25551 ∙ Uniprot:Q8ND04 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Alzahrani-Kuwahara syndrome (Moderate), mode of inheritance: AR
• Alzahrani-Kuwahara syndrome (Strong), mode of inheritance: AR
• Alzahrani-Kuwahara syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Alzahrani-Kuwahara syndrome	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	33242396

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMG8 gene.

• Alzahrani-Kuwahara syndrome (3 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMG8 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				6	1	7
missense			39	2	2	43
nonsense	2					2
start loss						0
frameshift	2	1				3
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1		2
Total	4	1	40	10	3

Variants in SMG8

This is a list of pathogenic ClinVar variants found in the SMG8 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-59210059-G-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
17-59210064-G-A		Inborn genetic diseases	Uncertain significance (Dec 02, 2022)
17-59210092-C-T		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
17-59210121-G-A		SMG8-related disorder • Inborn genetic diseases	Uncertain significance (Nov 13, 2024)
17-59210225-A-G			Likely benign (Jul 01, 2022)
17-59210230-T-C		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
17-59210233-A-T		Inborn genetic diseases	Uncertain significance (May 31, 2024)
17-59210310-G-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2024)
17-59210336-G-A			Likely benign (Nov 01, 2023)
17-59210377-G-C		Inborn genetic diseases	Uncertain significance (Oct 25, 2024)
17-59210401-G-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
17-59210407-G-C		Inborn genetic diseases	Uncertain significance (Sep 09, 2024)
17-59210444-C-T			Likely benign (Oct 01, 2024)
17-59210459-C-A		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
17-59210483-G-A			Likely benign (Aug 01, 2023)
17-59210489-C-CA		Alzahrani-Kuwahara syndrome	Pathogenic (Apr 19, 2021)
17-59210527-A-G		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
17-59210590-T-C		Inborn genetic diseases	Uncertain significance (Dec 04, 2024)
17-59210660-A-C			Likely benign (Aug 01, 2022)
17-59210663-CTCTG-C		Alzahrani-Kuwahara syndrome	Likely pathogenic (-)
17-59210665-C-CT		Alzahrani-Kuwahara syndrome	Likely pathogenic (-)
17-59210674-A-G		Alzahrani-Kuwahara syndrome	Pathogenic (Apr 19, 2021)
17-59210683-T-C			Uncertain significance (Jul 26, 2022)
17-59210688-G-C		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
17-59210694-C-A		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMG8	protein_coding	protein_coding	ENST00000543872	4	5848

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00726	0.993	125708	0	39	125747	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.73	416	528	0.788	0.0000261	6446
Missense in Polyphen		114	182.59	0.62433		2244
Synonymous	0.655	185	197	0.941	0.00000968	2009
Loss of Function	4.23	12	41.3	0.290	0.00000277	427

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000240	0.000239
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.000240	0.000196
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG9 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required to mediate the recruitment of SMG1 to the ribosome:SURF complex and to suppress SMG1 kinase activity until the ribosome:SURF complex locates the exon junction complex (EJC). Acts as a regulator of kinase activity. {ECO:0000269|PubMed:19417104}.
• Pathway: Metabolism of RNA;Nonsense-Mediated Decay (NMD);Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (Consensus)

Intolerance Scores

• rvis_EVS: -0.86
• rvis_percentile_EVS: 10.92

Haploinsufficiency Scores

• pHI: 0.297
• hipred: Y
• hipred_score: 0.519
• ghis: 0.593

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smg8

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;regulation of protein kinase activity
• Cellular component: cellular_component;cytosol
• Molecular function: protein binding