SMG9

Protein identityUniProt · HPA

UniProt accession

Q9H0W8

Gene

SMG9

Ensembl

ENSG00000105771

Chromosome

19

Canonical length

520 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Vesicles,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

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. Mutations in this gene cause a multiple congenital anomaly syndrome in human patients, characterized by brain malformation, congenital heart disease and other features. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

520 residues, UniProt reviewed canonical sequence.

>Q9H0W8|SMG9
     1  MSESGHSQPG LYGIERRRRW KEPGSGGPQN LSGPGGRERD YIAPWERERR DASEETSTSV
    61  MQKTPIILSK PPAERSKQPP PPTAPAAPPA PAPLEKPIVL MKPREEGKGP VAVTGASTPE
   121  GTAPPPPAAP APPKGEKEGQ RPTQPVYQIQ NRGMGTAAPA AMDPVVGQAK LLPPERMKHS
   181  IKLVDDQMNW CDSAIEYLLD QTDVLVVGVL GLQGTGKSMV MSLLSANTPE EDQRTYVFRA
   241  QSAEMKERGG NQTSGIDFFI TQERIVFLDT QPILSPSILD HLINNDRKLP PEYNLPHTYV
   301  EMQSLQIAAF LFTVCHVVIV VQDWFTDLSL YRFLQTAEMV KPSTPSPSHE SSSSSGSDEG
   361  TEYYPHLVFL QNKARREDFC PRKLRQMHLM IDQLMAHSHL RYKGTLSMLQ CNVFPGLPPD
   421  FLDSEVNLFL VPFMDSEAES ENPPRAGPGS SPLFSLLPGY RGHPSFQSLV SKLRSQVMSM
   481  ARPQLSHTIL TEKNWFHYAA RIWDGVRKSS ALAEYSRLLA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SMG9 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.44

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SMG9.

Disease | AllUniProt

Conditions SMG9 is implicated in, by any mechanism.

• Heart and brain malformation syndrome (HBMS) MIM:616920
• Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies (NEDITPO) MIM:619995

Disease | GeneticClinVar

16 pathogenic / likely-pathogenic of 149 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies
• Heart and brain malformation syndrome
• Brainstem dysplasia
• Abnormal cardiovascular system morphology
• Abnormal facial shape

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.1

gnomAD pLI

0

gnomAD missense Z

1.6

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• brain development
• eye development
• heart development
• in utero embryonic development
• negative regulation of apoptotic process
• nuclear-transcribed mRNA catabolic process, nonsense-mediated decay

Molecular functions

• identical protein binding

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• P-loop containing nucleoside triphosphate hydrolase
• Nonsense-mediated mRNA decay factor SMG9

KeywordsUniProt

• Acetylation
• Intellectual disability
• Nonsense-mediated mRNA decay
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of SMG9 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DHX34
• SMG8