SHFL

protein-coding

shiftless antiviral inhibitor of ribosomal frameshifting

Gene summary

This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

Previous symbols:

C19orf66

MANE transcript

NM_018381.4

Inheritance

—

ClinVar variants

U:8B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr19:10,086,122-10,093,252

External References & Databases

Ensembl (ENSG00000130813)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 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 SHFL variants in ClinVar

2 Conditions Cataloged

not providedTotal: 2

not specifiedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018381.4. 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			2 clinvar	2 clinvar		4
missense			3 clinvar			3
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	8	2	0	10

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018381.4	RefSeq	NP_060851.2	8	MANE Select
ENST00000253110.16	Ensembl	ENSP00000253110.10	8	MANE Select
NM_001308277.2	RefSeq	NP_001295206.1	8	Standard
ENST00000397881.7	Ensembl	ENSP00000380978.3	6	Standard

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253110
Coding exons: 8
Length: 7131
Individuals with no LoFs: 124620
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 124628
p: 0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.14	109	192	0.566	0.0000127	1897
Missense (PolyPhen)		24	59.045	0.40647		614
Synonymous	0.287	67	70.1	0.956	0.00000416	550
Loss of Function	2.52	4	14.3	0.280	6.77e-7	160

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000056	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Exhibits antiviral activity against dengue virus (DENV) and can inhibit the replication of all DENV serotypes. May block the protein translation of DENV RNA via its association with cellular mRNA-binding proteins and viral RNA. Can also limit the replication of hepatitis C virus (HCV), West Nile virus (WNV), Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1) and human adenovirus (PubMed:26735137). {ECO:0000269|PubMed:26735137}.;

Intolerance Scores

RVIS EVS: -0.3
RVIS percentile EVS: 32.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N

Gene Damage Prediction

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