FRG1

protein-coding

FSHD region gene 1

Gene summary

This gene maps to a location 100 kb centromeric of the repeat units on chromosome 4q35 which are deleted in facioscapulohumeral muscular dystrophy (FSHD). It is evolutionarily conserved and has related sequences on multiple human chromosomes but DNA sequence analysis did not reveal any homology to known genes. In vivo studies demonstrate the encoded protein is localized to the nucleolus. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004477.3

Inheritance

—

ClinVar variants

P:1U:45B:7

Top phenotype

FRG1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr4:189,940,855-189,963,202

External References & Databases

Ensembl (ENSG00000109536)

Transcript & Mutation Effects

hg38 • Region Span ~22.3 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 FRG1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 35

FRG1-related disorderTotal: 4

not providedTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Pulmonary artery atresiaTotal: 1

CIC-rearranged sarcomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004477.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar		4
missense	1 clinvar		38 clinvar	3 clinvar		42
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	0	45	7	0	53

Highest pathogenic variant AF is 0.000025560148

Loading ClinVar variants...

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_004477.3	RefSeq	NP_004468.1	9	MANE Select
ENST00000226798.9	Ensembl	ENSP00000226798.4	9	MANE Select
ENST00000507103.1	Ensembl	ENSP00000462603.1	3	Standard
ENST00000524583.5	Ensembl	ENSP00000435067.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

mRNA splicing, via spliceosome
rRNA processing
muscle organ development

Molecular Function

RNA binding
protein binding
actin filament binding

Cellular Component

nucleolus
Cajal body
Z disc
striated muscle dense body
catalytic step 2 spliceosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000226798
Coding exons: 9
Length: 22417
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 56
Defined: 125747
p: 0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.182	117	123	0.954	0.00000576	1645
Missense (PolyPhen)		27	34.465	0.78339		475
Synonymous	0.614	36	41.0	0.878	0.00000210	413
Loss of Function	0.723	11	13.9	0.791	5.80e-7	203

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000050	0.000046	rare
European (Non-Finnish)	0.00027	0.00025	rare
South Asian	0.00060	0.00056	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to mRNA in a sequence-independent manner. May play a role in regulation of pre-mRNA splicing or in the assembly of rRNA into ribosomal subunits. May be involved in mRNA transport. May be involved in epigenetic regulation of muscle differentiation through regulation of activity of the histone-lysine N- methyltransferase KMT5B. {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:15060122, ECO:0000269|PubMed:20970242, ECO:0000269|PubMed:21699900, ECO:0000269|PubMed:23720823}.;

Recessive Scores

pRec: 0.139

Intolerance Scores

LoFtool: 0.975
RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.928

Gene Damage Prediction

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