GeneBe

PRMT6

protein-coding

protein arginine methyltransferase 6, the group of 7BS protein arginine methyltranferases

Gene summary

The protein encoded by this gene belongs to the arginine N-methyltransferase family, which catalyze the sequential transfer of methyl group from S-adenosyl-L-methionine to the side chain nitrogens of arginine residues within proteins, to form methylated arginine derivatives and S-adenosyl-L-homocysteine. This protein can catalyze both, the formation of omega-N monomethylarginine and asymmetrical dimethylarginine, with a strong preference for the latter. It specifically mediates the asymmetric dimethylation of Arg2 of histone H3, and the methylated form represents a specific tag for epigenetic transcriptional repression. This protein also forms a complex with, and methylates DNA polymerase beta, resulting in stimulation of polymerase activity by enhancing DNA binding and processivity. [provided by RefSeq, Sep 2011]

Previous symbols:
  • HRMT1L6

MANE transcript

NM_018137.3

Inheritance

—

ClinVar variants

U:71B:4

Top phenotype

PRMT6-related disorder

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr1:107,056,674-107,067,636

External References & Databases

Ensembl (ENSG00000198890)NCBI Gene (55170)OMIM (608274)HGNC:18241GenCCUniProt (Q96LA8)AlphaFoldClinVar (PRMT6)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~11.0 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 PRMT6 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 71
PRMT6-related disorderTotal: 3
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018137.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
 2
missense
71
clinvar
2
clinvar
 73
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00713175
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_018137.3RefSeqNP_060607.21MANE Select
ENST00000370078.2EnsemblENSP00000359095.11MANE Select
ENST00000650338.1EnsemblENSP00000497826.11Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
prmt6Danio rerio

Structure: epiboly

Quality: process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Gene expression (Transcription)
  • Generic Transcription Pathway
  • RNA Polymerase II Transcription
  • RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
  • RMTs methylate histone arginines

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • base-excision repair
  • regulation of transcription, DNA-templated
  • viral process
  • histone methylation

Molecular Function

  • chromatin binding
  • protein binding
  • histone-arginine N-methyltransferase activity
  • protein-arginine N-methyltransferase activity
  • protein-arginine omega-N monomethyltransferase activity

Cellular Component

  • nucleus
  • nucleoplasm
  • nucleolus
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000370078
Coding exons
1
Length
2650
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.2762132250.9480.00001012374
Missense (PolyPhen)5872.1340.80406782
Synonymous-2.041281021.260.00000470815
Loss of Function1.78612.90.4665.52e-7131

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910). Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910). Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a (PubMed:17898714, PubMed:18079182, PubMed:18077460). H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3) (PubMed:17898714, PubMed:18077460). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53 (PubMed:19509293). Repression of TP53 blocks cellular senescence (By similarity). Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity (PubMed:16600869). Methylates HMGA1 (PubMed:16157300, PubMed:16159886). Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator. May play a role in innate immunity against HIV-1 in case of infection by methylating and impairing the function of various HIV-1 proteins such as Tat, Rev and Nucleocapsid protein p7 (NC) (PubMed:17267505). Methylates GPS2, protecting GPS2 from ubiquitination and degradation (By similarity). {ECO:0000250|UniProtKB:Q6NZB1, ECO:0000269|PubMed:11724789, ECO:0000269|PubMed:16157300, ECO:0000269|PubMed:16159886, ECO:0000269|PubMed:16600869, ECO:0000269|PubMed:17267505, ECO:0000269|PubMed:17898714, ECO:0000269|PubMed:18077460, ECO:0000269|PubMed:18079182, ECO:0000269|PubMed:19405910, ECO:0000269|PubMed:19509293, ECO:0000269|PubMed:20047962}.;

Recessive Scores

pRec
0.202

Intolerance Scores

LoFtool
0.508
RVIS EVS
-0.4
RVIS percentile EVS
26.53

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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