PRMT8

protein-coding

protein arginine methyltransferase 8, the group of 7BS protein arginine methyltranferases

Gene summary

Arginine methylation is a widespread posttranslational modification mediated by arginine methyltransferases, such as PRMT8. Arginine methylation is involved in a number of cellular processes, including DNA repair, RNA transcription, signal transduction, protein compartmentalization, and possibly protein translation (Lee et al., 2005 [PubMed 16051612]).[supplied by OMIM, Mar 2008]

Previous symbols:

HRMT1L3
HRMT1L4

MANE transcript

NM_019854.5

Inheritance

—

ClinVar variants

U:34B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr12:3,381,349-3,593,973

External References & Databases

Ensembl (ENSG00000111218)

Transcript & Mutation Effects

hg38 • Region Span ~212.6 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 PRMT8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 28

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019854.5. 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			4 clinvar		3 clinvar	7
missense			28 clinvar	1 clinvar		29
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	34	1	3	38

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019854.5	RefSeq	NP_062828.3	10	MANE Select
ENST00000382622.4	Ensembl	ENSP00000372067.3	10	MANE Select
NM_001256536.1	RefSeq	NP_001243465.1	10	Standard
ENST00000452611.6	Ensembl	ENSP00000414507.2	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
prmt8b	Danio rerio	Structure: Purkinje cell Quality: decreased branchiness abnormal

Gene / Model

Organism

Observed Phenotype

prmt8b

Danio rerio

Structure: Purkinje cell

Quality: decreased branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
protein methylation
histone methylation
peptidyl-arginine methylation
peptidyl-arginine methylation, to asymmetrical-dimethyl arginine

Molecular Function

protein binding
histone-arginine N-methyltransferase activity
S-adenosylmethionine-dependent methyltransferase activity
protein-arginine omega-N monomethyltransferase activity
protein-arginine omega-N asymmetric methyltransferase activity

Cellular Component

nucleus
cytosol
plasma membrane
anchored component of the cytoplasmic side of the plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000382622
Coding exons: 10
Length: 212625
Individuals with no LoFs: 124782
Homozygous LoFs: 1
Heterozygous LoFs: 961
Defined: 125744
p: 0.00383

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.46	87	237	0.368	0.0000133	2619
Missense (PolyPhen)		8	73.01	0.10957		775
Synonymous	0.280	91	94.5	0.963	0.00000609	708
Loss of Function	3.82	2	20.8	0.0961	9.65e-7	244

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0013	notable
Latino/Admixed American	0.011	0.0090	notable
Ashkenazi Jewish	0.0077	0.0062	notable
East Asian	0.0031	0.0029	notable
Finnish	0.0042	0.0041	notable
European (Non-Finnish)	0.0023	0.0021	notable
South Asian	0.0056	0.0050	notable
Other	0.0070	0.0062	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: S-adenosyl-L-methionine-dependent and membrane- associated arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA) in proteins such as NIFK, myelin basic protein, histone H4, H2A and H2A/H2B dimer (PubMed:16051612, PubMed:17925405, PubMed:26876602, PubMed:26529540). Able to mono- and dimethylate EWS protein; however its precise role toward EWS remains unclear as it still interacts with fully methylated EWS (PubMed:18320585). {ECO:0000269|PubMed:16051612, ECO:0000269|PubMed:17925405, ECO:0000269|PubMed:18320585, ECO:0000269|PubMed:26529540, ECO:0000269|PubMed:26876602}.;

Recessive Scores

pRec: 0.128

Intolerance Scores

LoFtool: 0.278
RVIS EVS: -0.41
RVIS percentile EVS: 26.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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