FRG1

FSHD region gene 1

Basic information

Region (hg38): 4:189940855-189963202

Links

ENSG00000109536 ∙ NCBI:2483 ∙ OMIM:601278 ∙ HGNC:3954 ∙ Uniprot:Q14331 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FRG1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FRG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			17	1		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	2	0

Variants in FRG1

This is a list of pathogenic ClinVar variants found in the FRG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-189941037-A-G		not specified	Uncertain significance (Dec 21, 2022)
4-189941056-G-A		not specified	Uncertain significance (Feb 12, 2025)
4-189943216-G-A		EBV-positive nodal T- and NK-cell lymphoma	Likely benign (-)
4-189943221-G-A		not specified	Uncertain significance (Dec 07, 2024)
4-189943234-A-G		not specified	Uncertain significance (Aug 19, 2024)
4-189943255-C-T		not specified	Uncertain significance (Aug 14, 2024)
4-189943256-C-G			Likely benign (Dec 31, 2019)
4-189952169-G-C		not specified	Uncertain significance (Nov 10, 2024)
4-189952225-A-G		not specified	Uncertain significance (Jan 18, 2023)
4-189953075-G-A		FRG1-related disorder	Likely benign (Sep 21, 2022)
4-189953126-G-T		CIC-rearranged sarcoma	not provided (-)
4-189955041-G-A		Pulmonary artery atresia	Pathogenic (-)
4-189955087-G-A		FRG1-related disorder	Likely benign (Nov 11, 2021)
4-189955092-G-A		not specified	Uncertain significance (Mar 25, 2024)
4-189955136-A-T		not specified	Uncertain significance (Sep 06, 2023)
4-189955141-T-G		not specified	Uncertain significance (Feb 25, 2025)
4-189957506-A-T		FRG1-related disorder	Benign (Feb 13, 2023)
4-189960757-T-G		not specified	Uncertain significance (Jul 07, 2024)
4-189960773-C-T		not specified	Uncertain significance (Oct 20, 2024)
4-189960785-A-G		not specified	Uncertain significance (Sep 22, 2022)
4-189960787-G-A			Likely benign (Dec 31, 2019)
4-189960833-A-G		not specified	Uncertain significance (Jun 23, 2021)
4-189960837-T-C		FRG1-related disorder	Likely benign (Feb 16, 2023)
4-189961818-A-G		not specified	Benign/Likely benign (-)
4-189961863-G-A		not specified	Uncertain significance (Jul 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FRG1	protein_coding	protein_coding	ENST00000226798	9	22417

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.14e-7	0.456	125691	0	56	125747	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.182	117	123	0.954	0.00000576	1645
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000320	0.000306
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000505	0.0000462
European (Non-Finnish)	0.000268	0.000255
Middle Eastern	0.000109	0.000109
South Asian	0.000598	0.000555
Other	0.00	0.00

dbNSFP

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}.
• Pathway: miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.975
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.228
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Frg1

Gene ontology

• Biological process: mRNA splicing, via spliceosome;rRNA processing;muscle organ development
• Cellular component: nucleolus;Cajal body;Z disc;striated muscle dense body;catalytic step 2 spliceosome
• Molecular function: RNA binding;protein binding;actin filament binding