SMG5

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	1 clinvar		6
missense			135 clinvar	5 clinvar	1 clinvar	141
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	145	6	1	152

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015327.3	RefSeq	NP_056142.2	22	MANE Select
ENST00000361813.5	Ensembl	ENSP00000355261.5	22	MANE Select
NM_001323614.2	RefSeq	NP_001310543.1	21	Standard
NM_001323615.2	RefSeq	NP_001310544.1	21	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
smg5	Danio rerio	Structure: extension Quality: decreased thickness abnormal

Gene / Model

Organism

Observed Phenotype

smg5

Danio rerio

Structure: extension

Quality: decreased thickness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA surveillance pathway - Homo sapiens (human)
Regulation of Telomerase
Signaling events mediated by HDAC Class I

Biological Process

nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
mRNA export from nucleus
telomere maintenance via telomerase
regulation of telomere maintenance
regulation of telomere maintenance via telomerase

Molecular Function

protein binding
ubiquitin protein ligase binding
telomeric DNA binding
histone deacetylase binding
protein phosphatase 2A binding

Cellular Component

nucleus
telomerase holoenzyme complex
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361813
Coding exons: 22
Length: 33606
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	510	587	0.869	0.0000345	6627
Missense (PolyPhen)		129	171.16	0.75368		1949
Synonymous	-0.225	229	225	1.02	0.0000123	1994
Loss of Function	5.08	15	56.1	0.268	0.00000317	614

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00022	0.00022	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000099	0.000097	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in nonsense-mediated mRNA decay. Does not have RNase activity by itself. Promotes dephosphorylation of UPF1. Together with SMG7 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Necessary for TERT activity. {ECO:0000269|PubMed:17053788}.;

Recessive Scores

pRec: 0.126

Intolerance Scores

LoFtool: 0.506
RVIS EVS: -1.02
RVIS percentile EVS: 8.14

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.202

Gene Damage Prediction

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