FRG2

Summary

FRG2 (FSHD region gene 2, HGNC:19136) is a protein-coding gene on chromosome 4q35.2, encoding Protein FRG2 (Q64ET8).

Predicted to be located in nucleus.

Source: NCBI Gene 448831 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_001286820

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19136
Approved symbol	FRG2
Name	FSHD region gene 2
Location	4q35.2
Locus type	gene with protein product
Status	Approved
Aliases	FRG2A
Ensembl gene	ENSG00000205097
Ensembl biotype	protein_coding
OMIM	609032
Entrez	448831

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000378763, ENST00000504750

RefSeq mRNA: 2 — MANE Select: NM_001286820 NM_001005217, NM_001286820

CCDS: CCDS34123, CCDS68834

Canonical transcript exons

ENST00000504750 — 4 exons

Exon	Start	End
ENSE00001478654	190024367	190026066
ENSE00002442551	190026384	190026461
ENSE00002469271	190027027	190027256
ENSE00002478187	190026691	190026768

Expression profiles

Bgee: expression breadth broad, 12 present calls, max score 52.96.

Top tissues by expression

107 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	52.96	silver quality
right hemisphere of cerebellum	UBERON:0014890	47.24	gold quality
cerebellum	UBERON:0002037	46.92	gold quality
cerebellar hemisphere	UBERON:0002245	46.92	gold quality
cerebellar cortex	UBERON:0002129	46.90	gold quality
sural nerve	UBERON:0015488	45.26	gold quality
skin of abdomen	UBERON:0001416	42.29	gold quality
zone of skin	UBERON:0000014	39.16	gold quality
bone marrow cell	CL:0002092	38.18	gold quality
endometrium	UBERON:0001295	38.01	silver quality
bone marrow	UBERON:0002371	37.40	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skin of leg	UBERON:0001511	36.74	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
placenta	UBERON:0001987	36.46	silver quality
skeletal muscle tissue	UBERON:0001134	36.34	gold quality
muscle tissue	UBERON:0002385	35.49	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
prefrontal cortex	UBERON:0000451	34.25	gold quality
right coronary artery	UBERON:0001625	34.03	gold quality
smooth muscle tissue	UBERON:0001135	32.90	gold quality
liver	UBERON:0002107	32.30	gold quality
tonsil	UBERON:0002372	32.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
leukocyte	CL:0000738	31.07	gold quality
muscle of leg	UBERON:0001383	31.07	gold quality
monocyte	CL:0000576	30.88	gold quality
blood	UBERON:0000178	30.80	gold quality
primary visual cortex	UBERON:0002436	30.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	35.08
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting FRG2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-651-5P	99.64	68.49	1104

Literature-anchored findings (GeneRIF, showing 4)

• FRG2 is upregulated in differentiating myoblast cultures of autosomal dominant facioscapulohumeral muscular dystrophy patients. (PMID:15520407)
• Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process. (PMID:20975055)
• new insights into the gene deregulation characterizing both FSHD-1 and FSHD-2, in which miRNAs may play a role (PMID:21695143)
• Study showed that the variability in clinical severity of facioscapulohumeral muscular dystrophy in FSHD1 and FSHD2 individuals is dependent on individual differences in susceptibility to D4Z4 hypomethylation. (PMID:25256356)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Frg2f1	ENSMUSG00000087385

Paralogs (2): FRG2C (ENSG00000172969), FRG2B (ENSG00000225899)

Protein

Protein identifiers

Protein FRG2 — Q64ET8 (reviewed: Q64ET8)

Alternative names: FSHD region gene 2 protein

All UniProt accessions (1): Q64ET8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Expression is undetectable in all tissues tested except for differentiating myoblasts of FSHD patients, which display low, yet distinct levels of expression, partly from FRG2, but predominantly originating from its homolog on chromosome 10.

Similarity. Belongs to the FRG2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q64ET8-1	1	yes
Q64ET8-2	2

RefSeq proteins (2): NP_001005217, NP_001273749* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026245	FRG2	Family

Pfam: PF15315

UniProt features (10 total): compositionally biased region 5, region of interest 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q64ET8-F1	60.35	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): chr4q35, MIR3662, MIR616_5P, MIR371B_5P, MIR373_5P, MIR3646, MIR95_5P, MIR655_3P, MIR374C_5P, MIR203A_3P, MIR93_3P, MIR215_3P, MIR6839_5P, MIR3668, MIR6505_3P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FRG2	FRG1	Q14331	987
FRG2	DUX4L2	P0CJ85	940
FRG2	MTMR1	Q13613	761
FRG2	TNNT3	P45378	739
FRG2	KLKB1	P03952	624
FRG2	NUCLEOLIN	P19338	619
FRG2	YY1	P25490	578
FRG2	SLC25A4	P12235	576
FRG2	MYOD1	P15172	528
FRG2	FAM149A	A5PLN7	506
FRG2	TRIML1	Q8N9V2	479
FRG2	FXR1	P51114	437
FRG2	SMCHD1	A6NHR9	434
FRG2	SLC25A5	P05141	429
FRG2	DDB1	Q16531	425

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FRG2	API5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): API5 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8I316, A0A286YDK6, A2A8T7, A5WWA0, A6H7B4, A6NFA0, A6NFR6, A6NGY1, A6NKB5, A6QP24, A8MX80, B2RQL2, O93343, P0C6A0, Q0VD86, Q1EHW4, Q1RN00, Q2HR82, Q32LI3, Q32LN6, Q3B8N5, Q49AJ0, Q5BMD4, Q5DU28, Q5NCP0, Q5SSZ7, Q64ET8, Q66H53, Q68DV7, Q68US1, Q6P4J6, Q6PE65, Q6PG16, Q7SYV9, Q80U22, Q80VY2, Q80W69, Q8BII1, Q8K2F3, Q8N2Y8

Diamond homologs: A6NGY1, Q64ET8, Q96QU4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

24 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

179 predictions. Top by Δscore:

Variant	Effect	Δscore
4:190026067:C:CC	acceptor_gain	1.0000
4:190026462:C:CC	acceptor_gain	1.0000
4:190026685:TCTTA:T	donor_gain	1.0000
4:190026686:CTTAC:C	donor_gain	1.0000
4:190026687:TTA:T	donor_loss	1.0000
4:190026687:TTACC:T	donor_gain	1.0000
4:190026688:TA:T	donor_loss	1.0000
4:190026688:TACCT:T	donor_gain	1.0000
4:190026766:CTG:C	acceptor_gain	1.0000
4:190026769:C:CC	acceptor_gain	1.0000
4:190027024:TA:T	donor_loss	1.0000
4:190027026:C:A	donor_loss	1.0000
4:190027026:CCTTG:C	donor_gain	1.0000
4:190026062:GTTCC:G	acceptor_gain	0.9900
4:190026063:TTCC:T	acceptor_gain	0.9900
4:190026064:TCC:T	acceptor_gain	0.9900
4:190026064:TCCC:T	acceptor_loss	0.9900
4:190026065:CC:C	acceptor_gain	0.9900
4:190026065:CCC:C	acceptor_gain	0.9900
4:190026065:CCCTG:C	acceptor_loss	0.9900
4:190026066:CC:C	acceptor_gain	0.9900
4:190026066:CCTG:C	acceptor_loss	0.9900
4:190026068:T:A	acceptor_loss	0.9900
4:190026378:TTCTA:T	donor_loss	0.9900
4:190026379:TCTA:T	donor_loss	0.9900
4:190026380:CTA:C	donor_loss	0.9900
4:190026381:TA:T	donor_loss	0.9900
4:190026382:A:G	donor_loss	0.9900
4:190026383:C:CT	donor_loss	0.9900
4:190026383:CCTG:C	donor_gain	0.9900

AlphaMissense

1814 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:190025716:C:G	A228P	0.924
4:190025693:G:C	F235L	0.901
4:190025693:G:T	F235L	0.901
4:190025695:A:G	F235L	0.901
4:190025845:C:G	A185P	0.891
4:190025680:A:G	W240R	0.889
4:190025680:A:T	W240R	0.889
4:190025715:G:T	A228D	0.881
4:190025707:C:G	A231P	0.857
4:190025725:A:C	Y225D	0.857
4:190025851:A:G	S183P	0.844
4:190025703:G:T	A232D	0.841
4:190025694:A:G	F235S	0.830
4:190025874:A:G	L175S	0.830
4:190025678:C:A	W240C	0.825
4:190025678:C:G	W240C	0.825
4:190025704:C:G	A232P	0.818
4:190025859:C:G	R180P	0.818
4:190025708:C:A	Q230H	0.799
4:190025708:C:G	Q230H	0.799
4:190025839:A:C	Y187D	0.793
4:190025706:G:T	A231E	0.784
4:190025829:A:G	L190P	0.777
4:190025862:A:T	V179E	0.773
4:190025831:G:C	D189E	0.770
4:190025831:G:T	D189E	0.770
4:190025760:A:G	L213P	0.757
4:190025769:A:G	L210P	0.752
4:190025833:C:G	D189H	0.748
4:190025841:A:T	V186D	0.746

dbSNP variants (sampled 300 via entrez): RS112322489 (4:190028037 A>AT), RS112907182 (4:190025754 C>G,T), RS113647878 (4:190028399 C>G,T), RS113699988 (4:190026911 G>A,T), RS1156308950 (4:190027278 C>A,G,T), RS1156511247 (4:190026256 A>C), RS1156650602 (4:190029199 C>A,T), RS1157762345 (4:190025831 G>A,T), RS1157989026 (4:190024838 C>T), RS1158117146 (4:190027647 T>C), RS1158149554 (4:190025758 G>A,T), RS1158303578 (4:190024031 GT>G), RS1158319529 (4:190026646 T>C), RS1158961177 (4:190028456 C>A), RS1159928996 (4:190028182 G>C)

Disease associations

OMIM: gene MIM:609032 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003160_4	Subjective response to lithium treatment in bipolar disorder	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
licochalcone B	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Plant Oils	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.