SMG6

protein-coding

SMG6 nonsense mediated mRNA decay factor, the group of Endoribonucleases

Gene summary

This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014]

Previous symbols:

C17orf31

MANE transcript

NM_017575.5

Inheritance

—

ClinVar variants

U:254B:20

Top phenotype

Corpus callosum agenesis-abnormal genitalia syndrome

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr17:2,059,839-2,303,785

External References & Databases

Ensembl (ENSG00000070366)

Transcript & Mutation Effects

hg38 • Region Span ~243.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMG6 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 249

not providedTotal: 12

Corpus callosum agenesis-abnormal genitalia syndromeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017575.5. Only rare variants are included.

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			6 clinvar	5 clinvar	1 clinvar	12
missense			240 clinvar	10 clinvar	4 clinvar	254
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	254	15	5	274

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017575.5	RefSeq	NP_060045.4	19	MANE Select
ENST00000263073.11	Ensembl	ENSP00000263073.5	19	MANE Select
NM_001256827.2	RefSeq	NP_001243756.1	10	Standard
NM_001256828.1	RefSeq	NP_001243757.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
smg6	Danio rerio	Structure: extension Quality: decreased thickness abnormal

Gene / Model

Organism

Observed Phenotype

smg6

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

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

RNA binding
endoribonuclease activity
protein binding
telomeric DNA binding
ribonucleoprotein complex binding

Cellular Component

chromosome, telomeric region
nucleus
telomerase holoenzyme complex
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263073
Coding exons: 19
Length: 243933
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.178	820	834	0.983	0.0000530	9251
Missense (PolyPhen)		269	331.94	0.81039		3583
Synonymous	-2.27	373	321	1.16	0.0000191	2809
Loss of Function	6.10	12	65.1	0.184	0.00000376	745

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini (PubMed:19179534). May have a general role in telomere regulation (PubMed:12676087, PubMed:12699629). Promotes in vitro the ability of TERT to elongate telomeres (PubMed:12676087, PubMed:12699629). Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization (PubMed:12676087, PubMed:12699629). Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER) (PubMed:12676087, PubMed:12699629). {ECO:0000269|PubMed:12676087, ECO:0000269|PubMed:12699629, ECO:0000269|PubMed:19179534}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.240
RVIS EVS: -0.16
RVIS percentile EVS: 42.06

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.497

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High