PRMT7

protein-coding

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

Gene summary

This gene encodes a member of the protein arginine N-methyltransferase family of proteins. The encoded enzyme transfers single methyl groups to arginine residues to generate monomethylarginines on histone proteins as well as other protein substrates. This enzyme plays a role in a wide range of biological processes, including neuronal differentiation, male germ line imprinting, small nuclear ribonucleoprotein biogenesis, and regulation of the Wnt signaling pathway. Mutations in this gene underlie multiple related syndromes in human patients characterized by intellectual disability, short stature and other features. The encoded protein may promote breast cancer cell invasion and metastasis in human patients. [provided by RefSeq, May 2017]

MANE transcript

NM_019023.5

Inheritance

ClinVar variants

P:53U:167B:87

Top phenotype

Short stature, brachydactyly, intellectual developmental disability, and seizures

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr16:68,310,951-68,360,852

External References & Databases

Ensembl (ENSG00000132600)

Transcript & Mutation Effects

hg38 • Region Span ~49.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

short stature-brachydactyly-obesity-global developmental delay syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014944

Submitter: PanelApp Australia

short stature-brachydactyly-obesity-global developmental delay syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014944

Submitter: Labcorp Genetics (formerly Invitae)

short stature-brachydactyly-obesity-global developmental delay syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014944

Submitter: Orphanet

short stature-brachydactyly-obesity-global developmental delay syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014944

Submitter: G2P

Clinical Genomic Database (CGD)

Short stature, brachydactyly, intellectual developmental disability, and seizuresAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed mediCONDITIONScal decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26437029

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRMT7 variants in ClinVar

22 Conditions Cataloged

not providedTotal: 196

Inborn genetic diseasesTotal: 120

Short stature-brachydactyly-obesity-global developmental delay syndromeTotal: 66

not specifiedTotal: 39

PRMT7-related disorderTotal: 25

Self-injurious behaviorTotal: 2

ObesityTotal: 2

HyperlipidemiaTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019023.5. 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			5 clinvar	66 clinvar	3 clinvar	74
missense	1 clinvar	10 clinvar	152 clinvar	17 clinvar	1 clinvar	181
nonsense	10 clinvar	4 clinvar	1 clinvar			15
start loss						0
frameshift	9 clinvar	10 clinvar	1 clinvar			20
splice donor/acceptor (+/-2bp)	1 clinvar	8 clinvar	8 clinvar			17
Total	21	32	167	83	4	307

Highest pathogenic variant AF is 0.00012892397

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 161 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019023.5	RefSeq	NP_061896.1	17	MANE Select
ENST00000441236.3	Ensembl	ENSP00000409324.2	17	MANE Select
NM_001184824.4	RefSeq	NP_001171753.1	16	Standard
NM_001290018.2	RefSeq	NP_001276947.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RMTs methylate histone arginines
Chromatin modifying enzymes
Chromatin organization

Biological Process

spliceosomal snRNP assembly
regulation of gene expression by genetic imprinting
regulation of transcription, DNA-templated
histone methylation
peptidyl-arginine methylation

Molecular Function

histone-arginine N-methyltransferase activity
S-adenosylmethionine-dependent methyltransferase activity
protein-arginine N-methyltransferase activity
[myelin basic protein]-arginine N-methyltransferase activity
protein-arginine omega-N monomethyltransferase activity

Cellular Component

fibrillar center
nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339507
Coding exons: 17
Length: 47590
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125748
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.683	386	426	0.907	0.0000261	4550
Missense (PolyPhen)		80	107.92	0.74132		1117
Synonymous	-0.734	190	178	1.07	0.0000122	1313
Loss of Function	1.62	28	38.9	0.720	0.00000192	417

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00028	0.00027	rare
Finnish	0.00010	0.000092	rare
European (Non-Finnish)	0.00050	0.00050	rare
South Asian	0.00030	0.00029	rare
Other	0.00049	0.00049	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), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Specifically mediates the symmetric dimethylation of histone H4 'Arg-3' to form H4R3me2s. Plays a role in gene imprinting by being recruited by CTCFL at the H19 imprinted control region (ICR) and methylating histone H4 to form H4R3me2s, possibly leading to recruit DNA methyltransferases at these sites. May also play a role in embryonic stem cell (ESC) pluripotency. Also able to mediate the arginine methylation of histone H2A and myelin basic protein (MBP) in vitro; the relevance of such results is however unclear in vivo. {ECO:0000269|PubMed:15044439, ECO:0000269|PubMed:15494416, ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:19110445}.;
Disease: DISEASE: Short stature, brachydactyly, intellectual developmental disability, and seizures (SBIDDS) [MIM:617157]: An autosomal recessive disease characterized by developmental delay, learning disabilities, mild mental retardation, delayed speech, and skeletal abnormalities. Skeletal features include short stature, brachydactyly, and short metacarpals and metatarsals. {ECO:0000269|PubMed:26437029}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.663
RVIS EVS: -1.9
RVIS percentile EVS: 1.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.924

Gene Damage Prediction

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