SMG9 (SMG9 nonsense mediated mRNA decay factor)

Gene

• Entrez ID: 56006
• Gene name: SMG9 nonsense mediated mRNA decay factor
• Gene symbol: SMG9
• Synonyms (NCBI Gene): C19orf61, F17127_1, HBMS, NEDITPO
• Chromosome: 19
• Chromosome location: 19q13.31
• Summary: This gene encodes a regulatory subunit of the SMG1 complex, which plays a critical role in nonsense-mediated mRNA decay (NMD). Binding of the encoded protein to the SMG1 complex kinase scaffold protein results in the inhibition of its kinase activity. Mut

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs869312741	GG>-	Likely-pathogenic, pathogenic	Frameshift variant, 5 prime UTR variant, coding sequence variant
rs869312742	T>C	Likely-pathogenic, pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2111238	hsa-miR-1276	CLIP-seq
MIRT2111239	hsa-miR-3158-3p	CLIP-seq
MIRT2111240	hsa-miR-3202	CLIP-seq
MIRT2111241	hsa-miR-323b-3p	CLIP-seq
MIRT2111242	hsa-miR-4311	CLIP-seq
MIRT2111243	hsa-miR-4747-5p	CLIP-seq
MIRT2111244	hsa-miR-5095	CLIP-seq
MIRT2111245	hsa-miR-583	CLIP-seq
MIRT2111246	hsa-miR-600	CLIP-seq
MIRT2111239	hsa-miR-3158-3p	CLIP-seq
MIRT2111240	hsa-miR-3202	CLIP-seq
MIRT2111243	hsa-miR-4747-5p	CLIP-seq
MIRT2111244	hsa-miR-5095	CLIP-seq
MIRT2111246	hsa-miR-600	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000184	Process	Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	IBA
GO:0000184	Process	Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	IEA
GO:0000184	Process	Nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	IMP	19417104
GO:0001654	Process	Eye development	IEA
GO:0001654	Process	Eye development	ISS
GO:0001701	Process	In utero embryonic development	IEA
GO:0005515	Function	Protein binding	IPI	19417104, 20817927, 25220460, 25416956, 26496610, 26841701, 32296183, 33205750
GO:0005829	Component	Cytosol	TAS
GO:0007420	Process	Brain development	IEA
GO:0007420	Process	Brain development	ISS
GO:0007507	Process	Heart development	IEA
GO:0007507	Process	Heart development	ISS
GO:0042802	Function	Identical protein binding	IPI	20817927
GO:0043066	Process	Negative regulation of apoptotic process	EXP	20817927

Other IDs

• MIM: 613176
• HGNC: 25763
• e!Ensembl: ENSG00000105771

Protein

• UniProt ID: Q9H0W8
• Protein name: Nonsense-mediated mRNA decay factor SMG9
• Protein 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
• PDB: 6L54, 6SYT, 6Z3R, 7PW4, 7PW5, 7PW7, 7PW8, 7PW9, 8FE7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10220	Smg8_Smg9	198 → 351	Smg8_Smg9	Family

• Sequence:

  MSESGHSQPGLYGIERRRRWKEPGSGGPQNLSGPGGRERDYIAPWERERRDASEETSTSV
  MQKTPIILSKPPAERSKQPPPPTAPAAPPAPAPLEKPIVLMKPREEGKGPVAVTGASTPE
  GTAPPPPAAPAPPKGEKEGQRPTQPVYQIQNRGMGTAAPAAMDPVVGQAKLLPPERMKHS
  IKLVDDQMNWCDSAIEYLLDQTDVLVVGVLGLQGTGKSMVMSLLSANTPEEDQRTYVFRA
  QSAEMKERGGNQTSGIDFFITQERIVFLDTQPILSPSILDHLINNDRKLPPEYNLPHTYV
  EMQSLQIAAFLFTVCHVVIVVQDWFTDLSLYRFLQTAEMVKPSTPSPSHESSSSSGSDEG
  TEYYPHLVFLQNKARREDFCPRKLRQMHLMIDQLMAHSHLRYKGTLSMLQCNVFPGLPPD
  FLDSEVNLFLVPFMDSEAESENPPRAGPGSSPLFSLLPGYRGHPSFQSLVSKLRSQVMSM
  ARPQLSHTILTEKNWFHYAARIWDGVRKSSALAEYSRLLA

• Sequence length: 520

Pathways

Reactome:

Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal cardiovascular system morphology	Likely pathogenic	rs869312741	RCV000210059	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Abnormal facial shape	Likely pathogenic	rs869312741	RCV000210059	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Brainstem dysplasia	Likely pathogenic	rs869312741	RCV000210059	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Likely pathogenic	rs869312741	RCV000210059	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Heart and brain malformation syndrome	Likely pathogenic; Pathogenic	rs869312741, rs1418644001, rs1968559161	RCV000210947 RCV003756641 RCV003152621	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental abnormality	Pathogenic	rs1968559161	RCV001264652	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies	Pathogenic	rs749498958, rs377252810	RCV002274864 RCV004587784	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Autism spectrum disorder	association	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SMG9-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Apraxias	Apraxia	Pubtator	35087184	Associate	★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	2434529	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	35321723	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	31390136		★☆☆☆☆ Found in Text Mining only
Dandy-Walker Syndrome	Dandy-Walker Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	31390136		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	33242396, 35087184	Associate	★☆☆☆☆ Found in Text Mining only
Facial Dysmorphism with Multiple Malformations	Facial dysmorphism syndrome	Pubtator	33242396	Associate	★☆☆☆☆ Found in Text Mining only
Gastroesophageal reflux disease	Gastroesophageal Reflux Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	CLINVAR_DG	27018474		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	BEFREE	31390136		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Growth Disorders	Growth disorder	Pubtator	35321723	Associate	★☆☆☆☆ Found in Text Mining only
HEART AND BRAIN MALFORMATION SYNDROME	Heart And Brain Malformation Syndrome	GENOMICS_ENGLAND_DG	27018474, 31390136		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HEART AND BRAIN MALFORMATION SYNDROME	Heart And Brain Malformation Syndrome	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HEART AND BRAIN MALFORMATION SYNDROME	Heart And Brain Malformation Syndrome	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Heart Defects Congenital	Congenital heart defect	Pubtator	33242396	Associate	★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	35087184, 35321723	Associate	★☆☆☆☆ Found in Text Mining only
Interrupted aortic arch	Interrupted aortic arch	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	31390136		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	33242396, 35321723	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	20872948		★☆☆☆☆ Found in Text Mining only
Posteriorly rotated ear	Posteriorly Rotated Ear	HPO_DG			★☆☆☆☆ Found in Text Mining only
Splenomegaly	Splenomegaly	Pubtator	2434529	Associate	★☆☆☆☆ Found in Text Mining only
Tremor	Tremor	Pubtator	35087184	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only