PRMT9

protein-coding

protein arginine methyltransferase 9, the group of 7BS protein arginine methyltranferases

Gene summary

This gene encodes a type II methyltransferase. Post-translational modification of target proteins by PRMTs plays an important regulatory role in many biological processes, whereby PRMTs methylate arginine residues by transferring methyl groups from S-adenosyl-L-methionine to the guanidino nitrogen atoms of arginine. The protein encoded by this gene methylates spliceosome associated protein 145 to regulate alternative splicing and acts as a modulator of small nuclear ribonucleoprotein maturation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2017]

Previous symbols:

PRMT10

MANE transcript

NM_138364.4

Inheritance

ClinVar variants

P:20U:114B:6

Top phenotype

Neurodevelopmental abnormality

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr4:147,637,785-147,684,163

External References & Databases

Ensembl (ENSG00000164169)

Transcript & Mutation Effects

hg38 • Region Span ~46.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

Mendelian neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100500

Submitter: PanelApp Australia

intellectual developmental disorder with dysmorphic facies and behavioral abnormalitiesLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0060760

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRMT9 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 115

Neurodevelopmental abnormalityTotal: 22

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 85Total: 8

not providedTotal: 6

PRMT9-associated neurodevelopmental disorderTotal: 3

PRMT9-related disorderTotal: 1

Meckel syndrome, type 9Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138364.4. 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
missense	1 clinvar	2 clinvar	111 clinvar	4 clinvar		118
nonsense	6 clinvar		1 clinvar			7
start loss						0
frameshift	10 clinvar		1 clinvar			11
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	18	2	114	6	0	140

Highest pathogenic variant AF is 0.000044628025

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138364.4	RefSeq	NP_612373.2	12	MANE Select
ENST00000322396.7	Ensembl	ENSP00000314396.6	12	MANE Select
NM_001304458.2	RefSeq	NP_001291387.1	10	Standard
NM_001350141.2	RefSeq	NP_001337070.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
mRNA processing
peptidyl-arginine methylation, to symmetrical-dimethyl arginine
peptidyl-arginine methylation, to asymmetrical-dimethyl arginine
histone arginine methylation

Molecular Function

protein binding
histone-arginine N-methyltransferase activity
protein-arginine N-methyltransferase activity
protein-arginine omega-N monomethyltransferase activity
protein-arginine omega-N asymmetric methyltransferase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000322396
Coding exons: 12
Length: 46446
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 72
Defined: 125748
p: 0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.28	376	453	0.831	0.0000218	5591
Missense (PolyPhen)		102	158.08	0.64523		1970
Synonymous	1.54	137	162	0.846	0.00000804	1591
Loss of Function	1.90	24	36.4	0.660	0.00000161	480

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00044	0.00044	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00033	0.00032	rare
South Asian	0.00029	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA). Specifically mediates the symmetrical dimethylation of SF3B2. Involved in the regulation of alternative splicing of pre-mRNA (PubMed:25737013, PubMed:25979344). {ECO:0000269|PubMed:25737013, ECO:0000269|PubMed:25979344}.;

Intolerance Scores

RVIS EVS: -0.84
RVIS percentile EVS: 11.45

Essentials

Essential (gene trap): N