PERM1

Summary

PERM1 (PPARGC1 and ESRR induced regulator, muscle 1, HGNC:28208) is a protein-coding gene on chromosome 1p36.33, encoding PGC-1 and ERR-induced regulator in muscle protein 1 (Q5SV97). Regulates the expression of selective PPARGC1A/B and ESRRA/B/G target genes with roles in glucose and lipid metabolism, energy transfer, contractile function, muscle mitochondrial biogenesis and oxidative capacity.

Involved in response to muscle activity. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 84808 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_001394713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28208
Approved symbol	PERM1
Name	PPARGC1 and ESRR induced regulator, muscle 1
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC13275, RP11-54O7.8
Ensembl gene	ENSG00000187642
Ensembl biotype	protein_coding
OMIM	615921
Entrez	84808

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000341290, ENST00000433179, ENST00000479361, ENST00000694917, ENST00000880867, ENST00000880868, ENST00000880869, ENST00000880870, ENST00000959770, ENST00000959771, ENST00000959772, ENST00000959773

RefSeq mRNA: 5 — MANE Select: NM_001394713 NM_001291366, NM_001291367, NM_001369897, NM_001369898, NM_001394713

CCDS: CCDS76083, CCDS90836

Canonical transcript exons

ENST00000433179 — 4 exons

Exon	Start	End
ENSE00001389758	978881	981173
ENSE00002263633	976499	976624
ENSE00003728856	982065	982093
ENSE00003963238	975198	976269

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 98.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6924 / max 125.5523, expressed in 60 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9674	0.5162	52
9675	0.1047	32
9673	0.0715	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.00	gold quality
gastrocnemius	UBERON:0001388	96.28	gold quality
left ventricle myocardium	UBERON:0006566	95.76	silver quality
heart left ventricle	UBERON:0002084	95.40	gold quality
cardiac ventricle	UBERON:0002082	95.13	gold quality
muscle of leg	UBERON:0001383	94.18	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.18	gold quality
lower esophagus mucosa	UBERON:0035834	91.80	gold quality
right atrium auricular region	UBERON:0006631	91.54	gold quality
cardiac atrium	UBERON:0002081	91.23	gold quality
kidney epithelium	UBERON:0004819	89.84	gold quality
skeletal muscle tissue	UBERON:0001134	89.09	gold quality
vastus lateralis	UBERON:0001379	88.81	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.65	gold quality
body of tongue	UBERON:0011876	87.88	gold quality
quadriceps femoris	UBERON:0001377	87.48	silver quality
heart	UBERON:0000948	86.91	gold quality
parotid gland	UBERON:0001831	86.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.13	gold quality
heart right ventricle	UBERON:0002080	84.92	silver quality
muscle tissue	UBERON:0002385	84.63	gold quality
biceps brachii	UBERON:0001507	84.28	gold quality
nasal cavity epithelium	UBERON:0005384	82.81	gold quality
upper arm skin	UBERON:0004263	82.73	gold quality
tongue	UBERON:0001723	82.43	gold quality
tendon of biceps brachii	UBERON:0008188	79.62	gold quality
vena cava	UBERON:0004087	78.68	gold quality
epithelial cell of pancreas	CL:0000083	78.66	gold quality
buccal mucosa cell	CL:0002336	76.46	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting PERM1, 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-3942-3P	99.57	69.03	2854
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-4662A-3P	97.02	67.77	941
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-6858-5P	96.05	64.59	1020

Literature-anchored findings (GeneRIF, showing 3)

• Proteomics evidence was identified for the PERM1 gene (PMID:24870542)
• These findings identify Perm1 as a muscle-specific regulator of exercise-induced signaling and Perm1 levels as tuners of the skeletal muscle response to exercise. (PMID:30862473)
• Perm1 regulates cardiac energetics as a downstream target of the histone methyltransferase Smyd1. (PMID:32574189)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	perm1b	ENSDARG00000076850
mus_musculus	Perm1	ENSMUSG00000078486
rattus_norvegicus	Perm1	ENSRNOG00000020244

Paralogs (1): PRRT3 (ENSG00000163704)

Protein

Protein identifiers

PGC-1 and ERR-induced regulator in muscle protein 1 — Q5SV97 (reviewed: Q5SV97)

Alternative names: PPARGC1 and ESRR-induced regulator in muscle 1, Peroxisome proliferator-activated receptor gamma coactivator 1 and estrogen-related receptor-induced regulator in muscle 1

All UniProt accessions (1): Q5SV97

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the expression of selective PPARGC1A/B and ESRRA/B/G target genes with roles in glucose and lipid metabolism, energy transfer, contractile function, muscle mitochondrial biogenesis and oxidative capacity. Required for the efficient induction of MT-CO2, MT-CO3, COX4I1, TFB1M, TFB2M, POLRMT and SIRT3 by PPARGC1A. Positively regulates the PPARGC1A/ESRRG-induced expression of CKMT2, TNNI3 and SLC2A4 and negatively regulates the PPARGC1A/ESRRG-induced expression of PDK4.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Muscle-specific expression is increased by endurance exercise.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5SV97-1	1	yes
Q5SV97-2	2
Q5SV97-3	3

RefSeq proteins (5): NP_001278295, NP_001278296, NP_001356826, NP_001356827, NP_001381642* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043442	Perm1	Family

UniProt features (22 total): compositionally biased region 10, sequence conflict 5, region of interest 4, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SV97-F1	44.94	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis

MSigDB gene sets: 15 (showing top): GOBP_RESPONSE_TO_MUSCLE_ACTIVITY, GOBP_RESPONSE_TO_ACTIVITY, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, chr1p36, YANG_BCL3_TARGETS_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_MITOCHONDRIAL_BIOGENESIS, REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE, REACTOME_TRANSCRIPTIONAL_ACTIVATION_OF_MITOCHONDRIAL_BIOGENESIS, RYBP_TARGET_GENES, MIR3942_3P, GSE14000_TRANSLATED_RNA_VS_MRNA_4H_LPS_DC_DN, HARALAMBIEVA_PBMC_M_M_R_II_AGE_11_22YO_VACCINATED_VS_UNVACCINATED_7YR_UP, WP_1P36_COPY_NUMBER_VARIATION_SYNDROME, GSE40666_UNTREATED_VS_IFNA_STIM_STAT1_KO_CD8_TCELL_90MIN_UP

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), response to muscle activity (GO:0014850)

GO Molecular Function (0):

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial biogenesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
response to activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PERM1	ANK2	Q01484	445
PERM1	TFB2M	Q9H5Q4	425
PERM1	KRTAP10-3	P60369	418
PERM1	ESRRG	P62508	406
PERM1	ESRRA	P11474	385
PERM1	PPARGC1A	Q9UBK2	364
PERM1	NDUFAF7	Q7L592	356
PERM1	NDUFAF2	Q8N183	353
PERM1	TTC16	Q8NEE8	331
PERM1	SLC7A1	P30825	328
PERM1	TMEM41A	Q96HV5	325
PERM1	CREG1	O75629	317
PERM1	MICOS13	Q5XKP0	307
PERM1	HRC	P23327	306
PERM1	TTLL11	Q8NHH1	304

IntAct

0 interactions, top by confidence:

BioGRID (2): PERM1 (Two-hybrid), PERM1 (Protein-peptide)

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A5D7L8, A6NDY0, A6NKD2, A7E321, E9PGG2, F6SZT2, O14771, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P17564, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q2M329, Q587J8, Q5DTT8, Q5R5G8, Q5R6R8, Q5SV97, Q60465, Q62881, Q69ZB3, Q6P752, Q86V59, Q8BSI6, Q8IWY8, Q8N3D4, Q8VD63

Diamond homologs: A5D7L8, Q149B8, Q5SV97

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

451 predictions. Top by Δscore:

Variant	Effect	Δscore
1:976265:CAAGG:C	acceptor_gain	0.9900
1:976270:C:CC	acceptor_gain	0.9900
1:976266:AAGG:A	acceptor_gain	0.9800
1:976267:AGG:A	acceptor_gain	0.9800
1:976268:GG:G	acceptor_gain	0.9800
1:976268:GGCTG:G	acceptor_loss	0.9700
1:976269:GCTGC:G	acceptor_loss	0.9700
1:976270:C:CA	acceptor_loss	0.9700
1:976271:T:G	acceptor_loss	0.9700
1:978876:CGTA:C	donor_loss	0.9400
1:978877:GTA:G	donor_loss	0.9400
1:978878:TACCT:T	donor_loss	0.9400
1:978879:A:C	donor_loss	0.9400
1:978880:C:CT	donor_loss	0.9400
1:979020:AAG:A	donor_gain	0.9400
1:978353:T:TA	donor_gain	0.9200
1:978875:ACGT:A	donor_loss	0.9200
1:978883:G:A	donor_gain	0.9200
1:976272:G:C	acceptor_loss	0.9100
1:978281:TAAGA:T	donor_gain	0.9000
1:979015:C:CA	donor_gain	0.9000
1:978879:ACCTG:A	donor_gain	0.8900
1:978880:CCTGC:C	donor_gain	0.8900
1:979145:TCG:T	donor_gain	0.8800
1:978874:CACGT:C	donor_loss	0.8700
1:979051:TAG:T	donor_gain	0.8700
1:979052:AGA:A	donor_gain	0.8700
1:978289:A:C	donor_gain	0.8600
1:979146:CG:C	donor_gain	0.8600
1:976273:CAAGA:C	acceptor_loss	0.8400

AlphaMissense

5038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:976508:A:G	W756R	0.990
1:976508:A:T	W756R	0.990
1:980976:G:C	F18L	0.987
1:980976:G:T	F18L	0.987
1:980978:A:G	F18L	0.987
1:976506:C:A	W756C	0.985
1:976506:C:G	W756C	0.985
1:980985:C:A	W15C	0.983
1:980985:C:G	W15C	0.983
1:976503:T:A	K757N	0.981
1:976503:T:G	K757N	0.981
1:980977:A:G	F18S	0.981
1:976504:T:A	K757I	0.980
1:976547:A:G	W743R	0.979
1:976547:A:T	W743R	0.979
1:976552:G:T	A741D	0.978
1:979512:G:C	F506L	0.978
1:979512:G:T	F506L	0.978
1:979514:A:G	F506L	0.978
1:976563:A:C	F737L	0.976
1:976563:A:T	F737L	0.976
1:976565:A:G	F737L	0.976
1:976545:C:A	W743C	0.975
1:976545:C:G	W743C	0.975
1:981018:G:C	F4L	0.973
1:981018:G:T	F4L	0.973
1:981020:A:G	F4L	0.973
1:979272:G:C	F586L	0.972
1:979272:G:T	F586L	0.972
1:979274:A:G	F586L	0.972

dbSNP variants (sampled 300 via entrez): RS1000018442 (1:982715 G>A), RS1000120877 (1:984068 G>A), RS1000608524 (1:979181 C>G,T), RS1001211743 (1:978338 G>A), RS1001523923 (1:978641 T>G), RS1001933039 (1:976476 C>T), RS1002221772 (1:981742 C>G), RS1002758216 (1:983563 G>A), RS1002896665 (1:976642 C>A,T), RS1003193701 (1:976714 A>C,G,T), RS1003324615 (1:983760 A>T), RS1003863211 (1:981067 G>A,T), RS1004002700 (1:975682 C>T), RS1004017158 (1:981836 G>A), RS1004115582 (1:976099 G>A)

Disease associations

OMIM: gene MIM:615921 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008513_1	Health literacy	6.000000e-06
GCST010241_352	Apolipoprotein A1 levels	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010104	health literacy measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
methyleugenol	decreases expression	1
kojic acid	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arbutin	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Folic Acid	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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