MAVS

protein-coding

mitochondrial antiviral signaling protein, the group of Caspase recruitment domain containing

Gene summary

This gene encodes an intermediary protein necessary in the virus-triggered beta interferon signaling pathways. It is required for activation of transcription factors which regulate expression of beta interferon and contributes to antiviral innate immunity. [provided by RefSeq, Jul 2020]

MANE transcript

NM_020746.5

Inheritance

—

ClinVar variants

U:62B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr20:3,846,799-3,876,123

External References & Databases

Ensembl (ENSG00000088888)

Transcript & Mutation Effects

hg38 • Region Span ~29.3 kb

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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 MAVS variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020746.5. 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				3 clinvar	2 clinvar	5
missense			59 clinvar	4 clinvar	1 clinvar	64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	62	7	3	72

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020746.5	RefSeq	NP_065797.2	6	MANE Select
ENST00000428216.4	Ensembl	ENSP00000401980.2	6	MANE Select
NM_001206491.2	RefSeq	NP_001193420.1	4	Standard
NM_001385663.1	RefSeq	NP_001372592.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Influenza A - Homo sapiens (human)
Cytosolic DNA-sensing pathway - Homo sapiens (human)
NOD-like receptor signaling pathway - Homo sapiens (human)
Hepatitis C - Homo sapiens (human)
Hepatitis B - Homo sapiens (human)

Biological Process

positive regulation of protein phosphorylation
activation of innate immune response
positive regulation of defense response to virus by host
positive regulation of myeloid dendritic cell cytokine production
regulation of transcription, DNA-templated

Molecular Function

protein binding
protein kinase binding
signaling adaptor activity
CARD domain binding

Cellular Component

mitochondrion
mitochondrial outer membrane
peroxisomal membrane
integral component of membrane
mitochondrial membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000428216
Coding exons: 6
Length: 21794
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125747
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.522	299	325	0.919	0.0000188	3432
Missense (PolyPhen)		65	74.703	0.87011		863
Synonymous	-0.134	143	141	1.01	0.00000849	1222
Loss of Function	0.752	11	14.0	0.783	7.62e-7	155

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for innate immune defense against viruses. Acts downstream of DHX33, DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon- independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon- dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis. {ECO:0000250|UniProtKB:Q8VCF0, ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20451243, ECO:0000269|PubMed:23087404}.;

Intolerance Scores

LoFtool: 0.864
RVIS EVS: 0.14
RVIS percentile EVS: 63.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.698

Gene Damage Prediction

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