Intellectual disability
Gene: PRMT9

PRMT9 (protein arginine methyltransferase 9)
EnsemblGeneIds (GRCh38): ENSG00000164169
EnsemblGeneIds (GRCh37): ENSG00000164169
OMIM: 616125, Gene2Phenotype
PRMT9 is in 3 panels

5 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of PRMT9 with syndromic intellectual disability (>20 unrelated families). Hence, this gene can be promoted to green rating in the next GMS update.
Created: 9 Jan 2026, 12:21 p.m. | Last Modified: 9 Jan 2026, 12:21 p.m.

Panel Version: 9.229

PMID:41260215 (2025) reported the identification of biallelic loss-of-function variants in PRMT9 gene in 35 individuals from 26 unrelated families primarily presenting with a neurodevelopmental disorder characterised by global developmental delay, learning disabilities, mild to severe intellectual disability, autism spectrum disorder, epilepsy, and hypotonia.

There were 26 different variants identified in total which included frameshifting indels, nonsense variants, missense variants, and two copy-number variants.

Global developmental delay was present un 33 individuals and mild - severe intellectual disability was present in 29 individuals (moderate and above in 11 patients, where ID was mild-moderate or severity not reported in others).

Functional evidence available from skin fibroblasts derived from affected individuals showed reduced expression at the RNA and/or protein level and subsequent aberrant methylation activity. Transcriptomic analysis of fibroblasts from affected individuals indicated differential expression of genes related to intellectual disability, autism, and cilia, suggesting a role of PRMT9 during ciliogenesis. Under ciliogenesis conditions, the skin-derived fibroblasts exhibited anomalies in the length of primary cilia but normal amounts of cilia. In addition, a prmt9 knockout zebrafish model displayed abnormal social preference in adult animals.

This gene has not yet been associated with relevant phenotypes in OMIM (last accessed 09 January 2026), but has been associated with 'Limited' rating on the DD panel in Gene2Phenotype.
Created: 9 Jan 2026, 12:18 p.m. | Last Modified: 9 Jan 2026, 12:18 p.m.

Panel Version: 9.227

PMID:21937992 reported a large WGS study on a cohort of 136 consanguineous families with autosomal-recessive intellectual disability, of which one family was identified with a homozygous missense variant in PRMT9 gene (p.Gly189Arg). No other phenotypic information is available about this patient.

PMID:38561334 reported functional studies characterising the p.Gly189Arg variant, which showed that this variant abolishes PRMT9 methyltransferase activity and reduces its protein stability. In addition, knock out mouse model showed PRMT9 loss in excitatory neurons leads to aberrant synapse development and impaired learning and memory.

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'limited' rating on the DD panel), but not yet in OMIM.

In summary, there is only one case with ID, but without detailed phenotypic information such as severity of ID, and with supportive functional evidence and mouse model. This gene should be rated red with the current evidence.
Created: 23 Jul 2025, 1:01 p.m. | Last Modified: 23 Jul 2025, 1:01 p.m.

Panel Version: 9.43

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

Created: 23 Jul 2025, 1:01 p.m.
Last Modified: 23 Jul 2025, 1:01 p.m.
Panel version: 9.227

Shahryar Alavi (UCL Queen Square Institute of Neurology)

I don't know

We detected a homozygous loss of function variant, p.(Arg359Ter), in the PRMT9 gene in a patient with intellectual disability and movement disorder. Parents are heterozygous.
It had been suggested that a missense variant in the PRMT9 gene, p.G189R, could be causative of intellectual disability (PMID: 21937992). Recently, another study has shown that p.G189R mutation reduces PRMT9 protein stability, and Prmt9 conditional knockout mice has impaired learning (PMID: 38561334).
Indeed, further cases are needed for deep phenotyping.
Created: 30 Apr 2025, 11:09 a.m. | Last Modified: 30 Apr 2025, 11:09 a.m.

Panel Version: 8.243

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
intellectual disability; failure to thrive

Publications

PMID: 38561334

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Created: 30 Apr 2025, 11:09 a.m.
Last Modified: 30 Apr 2025, 11:09 a.m.
Panel version: 8.243

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

There is currently no evidence to suggest there is an association of this gene with intellectual disability.
Created: 18 Dec 2017, 3:39 p.m.

Created: 18 Dec 2017, 3:39 p.m.

Panel version: Imported from Intellectual disability update Dec 2017 panel version 0.40

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

21937992

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:07 a.m.

Panel version: 0.306

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber

Phenotypes

neurodevelopmental disorder, MONDO:0700092

Tags

Q1_26_promote_green

OMIM

616125

Clinvar variants

Variants in PRMT9

Penetrance

Complete

Publications

Panels with this gene