SMG9

SMG9 nonsense mediated mRNA decay factor, the group of SMG1 complex

Basic information

Region (hg38): 19:43727982-43754962

Previous symbols: [ "C19orf61" ]

Links

ENSG00000105771 ∙ NCBI:56006 ∙ OMIM:613176 ∙ HGNC:25763 ∙ Uniprot:Q9H0W8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heart and brain malformation syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Heart and brain malformation syndrome; Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Neurologic; Ophthalmologic	27018474; 35087184

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMG9 gene.

• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMG9 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				14	3	17
missense			36	3		39
nonsense	1	1				2
start loss						0
frameshift		2	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	4	1	6
non coding				2	1	3
Total	1	3	37	19	4

Variants in SMG9

This is a list of pathogenic ClinVar variants found in the SMG9 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-43731608-G-A			Likely benign (Mar 06, 2018)
19-43731651-C-G		Heart and brain malformation syndrome	Pathogenic (Feb 13, 2024)
19-43731657-C-T		Inborn genetic diseases	Uncertain significance (May 11, 2022)
19-43732878-C-T		SMG9-related disorder	Likely benign (Jan 29, 2024)
19-43732916-G-A		Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies	Pathogenic (Apr 10, 2024)
19-43732922-G-A		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
19-43732952-G-A		Inborn genetic diseases	Uncertain significance (Apr 08, 2024)
19-43732963-T-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
19-43732990-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
19-43733373-C-T			Benign/Likely benign (Jul 01, 2022)
19-43733388-C-T		SMG9-related disorder	Likely benign (Jun 26, 2020)
19-43733405-C-G		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
19-43733414-G-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2017)
19-43733419-G-A			Uncertain significance (Mar 01, 2024)
19-43733428-T-C			Uncertain significance (Jan 24, 2023)
19-43733627-C-T		SMG9-related disorder	Likely benign (May 22, 2023)
19-43733659-G-A		Neurodevelopmental abnormality • Heart and brain malformation syndrome	Pathogenic (Jan 18, 2023)
19-43733682-C-T		Heart and brain malformation syndrome	Benign/Likely benign (Sep 27, 2021)
19-43733692-G-A		Inborn genetic diseases	Uncertain significance (May 14, 2021)
19-43733712-C-T		Inborn genetic diseases	Uncertain significance (Apr 30, 2021)
19-43734380-G-T		SMG9-related disorder	Likely benign (Jan 31, 2020)
19-43734420-G-A		SMG9-related disorder	Likely benign (Oct 28, 2019)
19-43734424-C-A		Inborn genetic diseases	Uncertain significance (May 04, 2021)
19-43734429-T-G			Likely benign (Dec 31, 2019)
19-43734444-G-A		SMG9-related disorder	Benign (Nov 11, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMG9	protein_coding	protein_coding	ENST00000270066	13	23842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.46e-13	0.278	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	240	320	0.749	0.0000189	3369
Missense in Polyphen		54	84.374	0.64001		835
Synonymous	0.592	113	121	0.932	0.00000699	1058
Loss of Function	1.13	23	29.7	0.775	0.00000164	304

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000782	0.000656
Ashkenazi Jewish	0.000202	0.000198
East Asian	0.000492	0.000489
Finnish	0.000187	0.000185
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.000492	0.000489
South Asian	0.000263	0.000261
Other	0.000655	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:19417104). Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8 (PubMed:19417104). Plays a role in brain, heart, and eye development (By similarity). {ECO:0000250|UniProtKB:Q9DB90, ECO:0000269|PubMed:19417104}.
• Disease: DISEASE: Heart and brain malformation syndrome (HBMS) [MIM:616920]: An autosomal recessive syndrome characterized by multiple congenital anomalies such as cardiac defects, brain malformations, including cerebellar vermis hypoplasia, hypoplastic corpus callosum and Dandy-Walker malformation, profoundly delayed psychomotor development, microphthalmia, and facial dysmorphism. {ECO:0000269|PubMed:27018474}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of RNA;Nonsense-Mediated Decay (NMD);Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (Consensus)

Intolerance Scores

• rvis_EVS: -0.76
• rvis_percentile_EVS: 13.45

Haploinsufficiency Scores

• pHI: 0.129
• hipred: Y
• hipred_score: 0.564
• ghis: 0.583

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• 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: Smg9
• Phenotype: vision/eye phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear 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); skeleton phenotype; renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; 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); 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); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;eye development;brain development;heart development
• Cellular component: cytosol
• Molecular function: protein binding;identical protein binding