PAX7

Summary

PAX7 (paired box 7, HGNC:8621) is a protein-coding gene on chromosome 1p36.13, encoding Paired box protein Pax-7 (P23759). Transcription factor that is involved in the regulation of muscle stem cells proliferation, playing a role in myogenesis and muscle regeneration.

This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The specific function of the paired box 7 gene is unknown but speculated to involve tumor suppression since fusion of this gene with a forkhead domain family member has been associated with alveolar rhabdomyosarcoma. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5081 — RefSeq curated summary.

At a glance

• Gene–disease (curated): myopathy, congenital, progressive, with scoliosis (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 12
• Clinical variants (ClinVar): 119 total — 4 pathogenic
• Phenotypes (HPO): 30
• Transcription factor: yes — 20 downstream targets (CollecTRI)
• MANE Select transcript: NM_001135254

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8621
Approved symbol	PAX7
Name	paired box 7
Location	1p36.13
Locus type	gene with protein product
Status	Approved
Aliases	Hup1
Ensembl gene	ENSG00000009709
Ensembl biotype	protein_coding
OMIM	167410
Entrez	5081

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000375375, ENST00000400661, ENST00000420770, ENST00000713640, ENST00000713641, ENST00000713642, ENST00000966024

RefSeq mRNA: 3 — MANE Select: NM_001135254 NM_001135254, NM_002584, NM_013945

CCDS: CCDS186, CCDS44074, CCDS44075

Canonical transcript exons

ENST00000420770 — 9 exons

Exon	Start	End
ENSE00000753995	18634303	18634538
ENSE00000753996	18635111	18635240
ENSE00000753998	18636237	18636371
ENSE00000753999	18691754	18691953
ENSE00000754000	18700653	18700818
ENSE00000754001	18703094	18703296
ENSE00001544124	18744814	18748866
ENSE00001544125	18735632	18735878
ENSE00002079264	18630846	18631688

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 80.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5348 / max 97.2625, expressed in 137 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1034	0.2779	109
1038	0.0964	31
1036	0.0825	31
1037	0.0583	22
1035	0.0198	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	80.10	gold quality
nasal cavity epithelium	UBERON:0005384	78.88	gold quality
nasal cavity mucosa	UBERON:0001826	75.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	70.55	gold quality
muscle of leg	UBERON:0001383	68.05	gold quality
gastrocnemius	UBERON:0001388	67.90	gold quality
prefrontal cortex	UBERON:0000451	61.44	gold quality
skeletal muscle tissue	UBERON:0001134	61.31	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.31	gold quality
heart right ventricle	UBERON:0002080	58.63	gold quality
muscle tissue	UBERON:0002385	56.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	56.56	gold quality
frontal cortex	UBERON:0001870	56.25	gold quality
metanephric glomerulus	UBERON:0004736	55.97	gold quality
parotid gland	UBERON:0001831	55.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	54.36	gold quality
neocortex	UBERON:0001950	54.21	gold quality
right frontal lobe	UBERON:0002810	53.59	gold quality
quadriceps femoris	UBERON:0001377	52.13	gold quality
vastus lateralis	UBERON:0001379	51.84	gold quality
cerebral cortex	UBERON:0000956	51.17	gold quality
deltoid	UBERON:0001476	50.74	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
anterior cingulate cortex	UBERON:0009835	49.70	gold quality
skin of hip	UBERON:0001554	49.44	silver quality
cerebellar vermis	UBERON:0004720	49.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.79

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

20 targets.

Target	Regulation
AGER
CARM1
CCND3
CKM
DUX4
EIF3K
ENO3
FSD1
ID2	Activation
ID3	Activation
MSTN
MYF5	Unknown
MYOD1	Activation
MYOG
NOTCH1
NOTCH3
PAX3	Unknown
PAX7
PXN
TP53

JASPAR motifs

Motif	Name	Family
MA0680.1	PAX7	Paired plus homeo domain

JASPAR matrix evidence (PMIDs): PMID:10567552

Upstream regulators (CollecTRI, top): FOS, HBP1, MYOD1, MYOG, PAX7, SSRP1

Literature-anchored findings (GeneRIF, showing 40)

• PAX7-FKHR gene fusion is prognostic indicator for alveolar rhabdomyosarcoma. (PMID:12039929)
• expression of PAX7 is correlated with metastasis potential–REVIEW (PMID:12647804)
• elevated PAX7 expression indicates myogenic satellite cell origin for embryonal rhabdomyosarcoma (PMID:12865925)
• in the RD embryonal rhabdomyosarcoma cell line, expression of wild-type PAX7 is downregulated by PAX3-FKHR (PMID:15184910)
• PAX3, PAX7 and their fusions with FKHR are each expressed in rhabdomyosarcoma tumors as a consistent mixture of functionally distinct isoforms (PMID:15688409)
• PAX 7-FKHR fusion transcripts were positive in 2/7 of alveolar rhabdomyosarcoma patients, and were negative in embryonal rhabdomyosarcoma and Control tumors. (PMID:17285543)
• Significant differences in survival and clinical characteristics between PAX3-FKHR and PAX7-FKHR positive tumors were seen indicating their role in carcinogenesis. (PMID:17613043)
• An amplification event is required for the PAX7-FOXO1A chimeric transcript to reach a critical expression level. (PMID:17954266)
• there is ALK overexpression in rhabdomyosarcomas, most likely independent of PAX3/PAX7-FKHR fusion status (PMID:18788887)
• Detection of PAX3/7-FKHR fusion gene by one-step RT-PCR is useful in the diagnosis of rhabdomyosarcomas (RMS) and that AChR-gamma is overexpressed in Chinese RMS patients. (PMID:18988640)
• Results identified a differentiation-resistant skeletal muscle progenitor cell population that was Pax7+/desmin- and capable of self-renewal. (PMID:19097049)
• TAT analysis of all trios revealed two SNPs in PAX7 showing significant excess maternal transmission Isolated cleft lip with or without cleft palate (PMID:19142206)
• Transgenic Pax7 and MyoD are not essential for myogenic differentiation and participation of bone marrow-derived myogenic progenitors in muscle regeneration. (PMID:20333749)
• The clinical behavior and molecular characteristics of alveolar rhabdomyosarcoma without a PAX/FOXO1 fusion gene are indistinguishable from embryonal cases and significantly different from fusion-positive alveolar cases. (PMID:20351326)
• MyoD can play an active role in Alveolar rhabdomyosarcoma by augmenting Pax7-FKHR function. (PMID:21321994)
• results suggest that both Pax3 and Pax7 transcripts are required for commitment of cells to the myogenic lineage, with each transcript having a distinct role (PMID:21421465)
• Analysis of Pax7 expressing myogenic cells in zebrafish muscle development, injury and disease. (PMID:21954137)
• The presence of PAX3/7-FOXO1 translocation was significantly associated with a higher frequency of metastatic disease. (PMID:22089931)
• Detection of PAX3/PAX7-FKHR fusion transcripts is a novel tool for Rhabdomyosarcoma diagnosis (PMID:22197543)
• PAX7-FKHR fusion gene inhibits myogenic differentiation via NF-kappaB upregulation. (PMID:22374423)
• PAX3/7-FKHR gene fusions expression was detected in 56% of ARMS tumor samples. (PMID:23079386)
• High prevalence of 1p36 microdeletions in B-cell non-Hodgkin lymphomas is associated with PAX7 loss. (PMID:23205730)
• SUMOylation of Pax7 is essential for neural crest development in chick embryos and for the inhibitory roles of Pax7 in C2C12-muscle differentiation. (PMID:23247248)
• Our study replicated previous GWAS findings for markers in VAX1 in the Asian population, and identified rare variants in PAX7 and VAX1 that may contribute to the etiology of CL(P) (PMID:23463464)
• In addition, eight genes classified as ‘second tier’ hits in the original study (PAX7, THADA, COL8A1/FILIP1L, DCAF4L2, GADD45G, NTN1, RBFOX3 and FOXE1) showed evidence of linkage and association in this replication sample. (PMID:23512105)
• Pax7 responds to NF-kappaB by impairing the regenerative capacity of myogenic cells in the muscle microenvironment to drive muscle wasting in cancer. (PMID:24084740)
• RAGE upregulates myogenin which upregulates MyoD and downregulates PAX7, with consequent inhibition of proliferation and stimulation of differentiation. (PMID:24554430)
• these results suggest that sarcoma metastasis can be partially controlled through Pax7/MyoD-dependent activation of miR-182 and provide insight into the role that myogenic transcription factors have in sarcoma progression (PMID:26234681)
• Our results on Pax7 and MyoD protein expression suggest that proliferation and differentiation of skeletal muscle stem cells are affected in ALS patients, and the myogenic processes cannot overcome the denervation-induced wasting. (PMID:27195289)
• miR-206 acts as a tumor suppressor in fusion-negative RMS at least partially through downregulation of PAX7. (PMID:27277678)
• PAX7 expression is a useful marker of skeletal muscle differentiation in rhabdomyosarcoma, particularly of the embryonal subtype, with specificity for rhabdomyosarcoma and Ewing sarcoma. (PMID:27526298)
• NTN1 rs9788972 is identified as a risk locus for nonsyndromic orofacial clefts susceptibility in a northern Chinese population; SNPs in PAX7 were not associated with any increased risk (PMID:28489749)
• EWSR1 fusion protein is required for PAX7 expression in Ewing sarcoma and identify a candidate EWSR1-FLI1-bound PAX7 enhancer that coincides with both a consensus GGAA repeat-containing binding site and a peak of regulatory H3K27 acetylation. (PMID:28643791)
• Transfection experiments showed that the PAX7 splice-site mutation putatively causes nonsense-mediated mRNA decay affecting onlyPAX7 isoform 3. (PMID:28779497)
• The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain. (PMID:28935672)
• Data suggest that paired box gene 7 protein (PAX7) target gene repression is a hallmark of facioscapulohumeral muscular dystrophy (FSHD) that should be considered in the investigation of FSHD pathology and therapy. (PMID:29255294)
• we have confirmed PAX7 reactivity in most Ewing sarcoma cases (PMID:29920735)
• PAX7 target gene repression in facioscapulohumeral muscular dystrophy correlates with disease severity, independently of DUX4 target gene expression. At the single-cell level, PAX7 target gene repression can efficiently discriminate FSHD cells, even when no DUX4 target genes are detectable. (PMID:31067297)
• Our study confirmed that PAX7 is a strong candidate gene for nsCL/P [ cleft lip / cleft palate]. Nucleotide variants of this gene contribute to the etiology of nsCL/P in the homogenous Polish population. (PMID:31173442)
• Study identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5 and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration. (PMID:31852888)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pax7b	ENSDARG00000070818
danio_rerio	pax7a	ENSDARG00000100398
mus_musculus	Pax7	ENSMUSG00000028736
rattus_norvegicus	Pax7	ENSRNOG00000018739

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155), SHOX (ENSG00000185960)

Protein

Protein identifiers

Paired box protein Pax-7 — P23759 (reviewed: P23759)

Alternative names: HuP1

All UniProt accessions (3): P23759, A0AAQ5BGJ6, A0AAQ5BGK0

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that is involved in the regulation of muscle stem cells proliferation, playing a role in myogenesis and muscle regeneration.

Subunit / interactions. Can bind to DNA as a heterodimer with PAX3. Interacts with PAXBP1; the interaction links PAX7 to a WDR5-containing histone methyltransferase complex. Interacts with DAXX.

Subcellular location. Nucleus.

Post-translational modifications. Acetylation at Lys-105 and Lys-139 by KAT8 is required for high-level transcription factor activity. Deacetylated by SIRT2.

Disease relevance. Rhabdomyosarcoma 2 (RMS2) [MIM:268220] A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving PAX7 is found in rhabdomyosarcoma. Translocation t(1;13)(p36;q14) with FOXO1. The resulting protein is a transcriptional activator. Congenital myopathy 19 (CMYO19) [MIM:618578] An autosomal recessive muscular disorder characterized by infantile onset of progressive muscular atrophy, hypotonia, ptosis, scoliosis and dysmorphic facial features. Disease severity is variable, ranging from mild to severe. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the paired homeobox family.

Isoforms (3)

UniProt ID	Names	Canonical?
P23759-3	3	yes
P23759-1	1, Long
P23759-2	2, Short

RefSeq proteins (3): NP_001128726, NP_002575, NP_039236 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR001523	Paired_dom	Domain
IPR003654	OAR_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR022106	Pax7_C	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR043182	PAIRED_DNA-bd_site	Conserved_site
IPR043565	PAX_fam	Family

Pfam: PF00046, PF00292, PF12360

UniProt features (18 total): region of interest 5, sequence variant 3, DNA-binding region 2, modified residue 2, splice variant 2, chain 1, sequence conflict 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23759-F1	63.21	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 105, 139

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9834899	Specification of the neural plate border

MSigDB gene sets: 282 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, MORF_FLT1, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_CARTILAGE_DEVELOPMENT, MORF_MSH3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, LFA1_Q6, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, MORF_BRCA1, GOBP_GROWTH, AREB6_01

GO Biological Process (23): chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), nervous system development (GO:0007399), anatomical structure morphogenesis (GO:0009653), regulation of cell fate commitment (GO:0010453), skeletal muscle satellite cell commitment (GO:0014813), skeletal muscle satellite cell differentiation (GO:0014816), spinal cord association neuron differentiation (GO:0021527), dorsal/ventral neural tube patterning (GO:0021904), negative regulation of apoptotic process (GO:0043066), skeletal muscle tissue regeneration (GO:0043403), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate commitment (GO:0048663), embryonic skeletal system development (GO:0048706), cartilage development (GO:0051216), muscle tissue morphogenesis (GO:0060415), regulation of chromatin organization (GO:1902275), positive regulation of myoblast proliferation (GO:2000288), regulation of DNA-templated transcription (GO:0006355), muscle organ development (GO:0007517), skeletal muscle tissue development (GO:0007519), regulation of gene expression (GO:0010468)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Gastrulation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell fate commitment	3
chromatin organization	2
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
skeletal system development	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
system development	1
developmental process	1
anatomical structure development	1
regulation of developmental process	1
regulation of cellular process	1
skeletal muscle satellite cell differentiation	1
skeletal muscle cell differentiation	1
cell differentiation in spinal cord	1
dorsal spinal cord development	1
central nervous system neuron differentiation	1
dorsal/ventral pattern formation	1
neural tube patterning	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
tissue regeneration	1
positive regulation of DNA-templated transcription	1
neuron differentiation	1
chordate embryonic development	1
animal organ development	1
connective tissue development	1
muscle organ morphogenesis	1
tissue morphogenesis	1
regulation of cellular component organization	1
positive regulation of cell population proliferation	1
myoblast proliferation	1
regulation of myoblast proliferation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1

Protein interactions and networks

STRING

2698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAX7	MYOG	P15173	933
PAX7	FOXO1	Q12778	923
PAX7	MYOD1	P15172	900
PAX7	MYF5	P13349	896
PAX7	MYF6	P23409	836
PAX7	ASH2L	Q9UBL3	820
PAX7	SIX1	Q15475	744
PAX7	SNAI2	O43623	733
PAX7	SHH	Q15465	727
PAX7	SOX10	P56693	726
PAX7	MYH6	P13533	722
PAX7	MSTN	O14793	711
PAX7	CDH15	P55291	707
PAX7	CSRNP1	Q96S65	690
PAX7	BMP4	P12644	682

IntAct

14 interactions, top by confidence:

A	B	Type	Score
rep	PAX7	psi-mi:“MI:0915”(physical association)	0.490
NFIA	PAX7	psi-mi:“MI:0915”(physical association)	0.470
NFIB	PAX7	psi-mi:“MI:0915”(physical association)	0.470
NFIC	PAX7	psi-mi:“MI:0915”(physical association)	0.470
PAX7	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
PAX7	CRK	psi-mi:“MI:0915”(physical association)	0.400
SRC	PAX7	psi-mi:“MI:0915”(physical association)	0.400
FYN	PAX7	psi-mi:“MI:0915”(physical association)	0.400
NCK1	PAX7	psi-mi:“MI:0915”(physical association)	0.400
PAX7	CTTN	psi-mi:“MI:0914”(association)	0.350
PAX7	BCL9	psi-mi:“MI:2364”(proximity)	0.270
AKR1B1	PAX7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (135): NEDD4 (Affinity Capture-Western), NEDD4 (Reconstituted Complex), PAX7 (Biochemical Activity), PAX7 (Biochemical Activity), HOMER3 (Two-hybrid), MAGOHB (Two-hybrid), C1orf109 (Two-hybrid), CT55 (Two-hybrid), CIB1 (Two-hybrid), KRTAP19-7 (Two-hybrid), PAX7 (Two-hybrid), PAX7 (Two-hybrid), NFIB (Proximity Label-MS), KMT2D (Proximity Label-MS), KDM6A (Proximity Label-MS)

ESM2 similar proteins: A0JMA6, O08656, O57682, O57685, P06601, P09022, P23759, P23760, P24610, P32114, P47239, P47240, P47242, P49639, P51974, P55166, P55771, P70056, Q00288, Q02548, Q02650, Q02962, Q06710, Q0IH87, Q28D67, Q28DP6, Q2L4T2, Q2VL50, Q2VL51, Q2VL52, Q2VL53, Q2VL54, Q2VL57, Q2VL58, Q2VL59, Q2VL60, Q2VL62, Q32NP8, Q5R9M8, Q645N4

Diamond homologs: A0JMA6, G5ED14, G5ED66, G5EDS1, O18381, O43316, O57682, O57685, O73917, O88436, P06601, P09082, P09083, P09084, P15863, P23757, P23758, P23759, P23760, P24610, P26367, P26630, P32114, P32115, P47236, P47238, P47239, P47240, P47242, P51974, P55166, P55771, P55864, P63015, P63016, Q00288, Q02548, Q02650, Q02962, Q06710

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
PAX7	up-regulates	Quiescence
PAX7	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
RBPJ	up-regulates	PAX7	binding
CARM1	up-regulates	PAX7	methylation
PAX7	up-regulates	KMT2A	binding
PAX7	up-regulates	KMT2D	binding
PAX7	“form complex”	“PAX7/MLL1 complex”	binding
PAX7	“form complex”	“PAX7/MLL2 complex”	binding
PAX7	up-regulates	“MLL2 complex”	binding
PAX7	up-regulates	“MLL1 complex”	binding
RBPJ/NOTCH	“up-regulates quantity by expression”	PAX7	“transcriptional regulation”
PAX7	down-regulates	Skeletal_muscle_differentiation
NOTCH1	“up-regulates quantity by expression”	PAX7
NOTCH	“up-regulates quantity by expression”	PAX7
MIR1-1	“down-regulates quantity”	PAX7	“post transcriptional regulation”
ABL1	“up-regulates activity”	PAX7	phosphorylation
SUZ12/EZH2/YY1	“down-regulates quantity by repression”	PAX7	“transcriptional regulation”
PAX7	“down-regulates quantity by destabilization”	MYOD1
MYOG	“down-regulates quantity by destabilization”	PAX7
PAX7	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
mir-206	“down-regulates quantity”	PAX7	“post transcriptional regulation”
“Polycomb repressive complex 2”	“down-regulates quantity by repression”	PAX7	“transcriptional regulation”
PAX7	down-regulates	Differentiation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	80
Likely benign	21
Benign	8

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3775439	NM_001135254.2(PAX7):c.742G>T (p.Glu248Ter)	Pathogenic
689506	NM_001135254.2(PAX7):c.433C>T (p.Arg145Ter)	Pathogenic
689507	NM_001135254.2(PAX7):c.86-1G>A	Pathogenic
689509	NM_001135254.2(PAX7):c.166C>T (p.Arg56Cys)	Pathogenic

SpliceAI

2215 predictions. Top by Δscore:

Variant	Effect	Δscore
1:18631688:GGTA:G	donor_loss	1.0000
1:18631689:G:GA	donor_loss	1.0000
1:18631690:T:A	donor_loss	1.0000
1:18634535:CAGA:C	donor_gain	1.0000
1:18634536:AGA:A	donor_gain	1.0000
1:18634537:GA:G	donor_gain	1.0000
1:18634537:GAG:G	donor_gain	1.0000
1:18634538:AG:A	donor_loss	1.0000
1:18634539:G:GG	donor_gain	1.0000
1:18634539:GTG:G	donor_loss	1.0000
1:18634540:T:G	donor_loss	1.0000
1:18635087:A:AG	acceptor_gain	1.0000
1:18635088:C:G	acceptor_gain	1.0000
1:18635095:A:AG	acceptor_gain	1.0000
1:18635096:C:G	acceptor_gain	1.0000
1:18635101:A:AG	acceptor_gain	1.0000
1:18635102:C:G	acceptor_gain	1.0000
1:18635237:TCAGG:T	donor_loss	1.0000
1:18635238:CAG:C	donor_loss	1.0000
1:18635239:AGGT:A	donor_loss	1.0000
1:18635240:GG:G	donor_loss	1.0000
1:18635241:G:GC	donor_loss	1.0000
1:18635242:T:A	donor_loss	1.0000
1:18636225:T:TA	acceptor_gain	1.0000
1:18636228:A:AG	acceptor_gain	1.0000
1:18636229:T:G	acceptor_gain	1.0000
1:18636233:T:TA	acceptor_gain	1.0000
1:18691745:C:A	acceptor_gain	1.0000
1:18691746:G:A	acceptor_gain	1.0000
1:18691749:T:A	acceptor_gain	1.0000

AlphaMissense

3282 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:18634323:G:C	G36R	1.000
1:18634330:T:A	V38D	1.000
1:18634332:A:C	N39H	1.000
1:18634332:A:G	N39D	1.000
1:18634333:A:T	N39I	1.000
1:18634334:T:A	N39K	1.000
1:18634334:T:G	N39K	1.000
1:18634337:G:C	Q40H	1.000
1:18634337:G:T	Q40H	1.000
1:18634339:T:A	L41Q	1.000
1:18634339:T:C	L41P	1.000
1:18634341:G:A	G42R	1.000
1:18634341:G:C	G42R	1.000
1:18634342:G:A	G42E	1.000
1:18634342:G:T	G42V	1.000
1:18634344:G:A	G43R	1.000
1:18634344:G:C	G43R	1.000
1:18634344:G:T	G43W	1.000
1:18634345:G:A	G43E	1.000
1:18634345:G:T	G43V	1.000
1:18634350:T:A	F45I	1.000
1:18634350:T:C	F45L	1.000
1:18634350:T:G	F45V	1.000
1:18634351:T:C	F45S	1.000
1:18634351:T:G	F45C	1.000
1:18634352:C:A	F45L	1.000
1:18634352:C:G	F45L	1.000
1:18634354:T:A	I46N	1.000
1:18634354:T:C	I46T	1.000
1:18634354:T:G	I46S	1.000

dbSNP variants (sampled 300 via entrez): RS1000023777 (1:18688172 T>G), RS1000032874 (1:18630476 T>C), RS1000051670 (1:18635424 A>G), RS1000054966 (1:18687797 G>A), RS1000073908 (1:18651219 A>G), RS1000116083 (1:18672504 C>T), RS1000166935 (1:18727803 G>A), RS1000199360 (1:18742929 C>T), RS1000241878 (1:18704332 C>A), RS1000242860 (1:18687642 T>C), RS1000256229 (1:18652031 A>C), RS1000288829 (1:18692960 C>A,G,T), RS1000315364 (1:18712678 C>T), RS1000317631 (1:18738066 G>A), RS1000319945 (1:18723312 C>T)

Disease associations

OMIM: gene MIM:167410 | disease phenotypes: MIM:618578, MIM:268220

GenCC curated gene-disease

Disease	Classification	Inheritance
myopathy, congenital, progressive, with scoliosis	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital myopathy with myasthenic-like onset	Moderate	AR

Mondo (4): myopathy, congenital, progressive, with scoliosis (MONDO:0032821), congenital myopathy with myasthenic-like onset (MONDO:0018528), alveolar rhabdomyosarcoma (MONDO:0009994), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (4): Congenital myopathy with myasthenic-like onset (Orphanet:424107), Rhabdomyosarcoma (Orphanet:780), Alveolar rhabdomyosarcoma (Orphanet:99756), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000126	Hydronephrosis
HP:0000218	High palate
HP:0000297	Facial hypotonia
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000457	Depressed nasal ridge
HP:0000508	Ptosis
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001324	Muscle weakness
HP:0001442	Typified by somatic mosaicism
HP:0001558	Decreased fetal movement
HP:0001591	Bell-shaped thorax
HP:0002015	Dysphagia
HP:0002093	Respiratory insufficiency
HP:0002650	Scoliosis
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002803	Congenital contracture
HP:0003202	Skeletal muscle atrophy
HP:0006779	Alveolar rhabdomyosarcoma
HP:0007979	Gaze-evoked horizontal nystagmus
HP:0008936	Axial hypotonia
HP:0012585	Renal atrophy

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001628_26	Orofacial clefts	7.000000e-09
GCST001651_42	Response to amphetamines	2.000000e-06
GCST002021_3	Body mass index	8.000000e-06
GCST002830_23	Urate levels in lean individuals	9.000000e-06
GCST002942_3	Percentage gas trapping	1.000000e-06
GCST004166_35	Nonsyndromic cleft lip with cleft palate	4.000000e-07
GCST004881_5	Knee osteoarthritis	7.000000e-07
GCST010225_10	Cortical surface area (visual PC2)	3.000000e-08
GCST012337_1	Nonsyndromic cleft lip with or without cleft palate	3.000000e-08
GCST012362_1	Orofacial cleft x maternal periconceptional multivitamin use interaction (2df)	9.000000e-06
GCST012363_1	Orofacial cleft x maternal periconceptional alcohol use interaction (2df)	3.000000e-06
GCST012364_1	Orofacial cleft x maternal periconceptional smoking interaction (2df)	6.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0007628	gas trapping measurement
EFO:0003959	cleft lip
EFO:0004771	visual cortical surface area measurement
EFO:0009116	vitamin supplement exposure measurement
EFO:0006527	smoking status measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D018232	Rhabdomyosarcoma, Alveolar	C04.557.450.590.550.660.665; C04.557.450.795.550.660.665

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
bisphenol A	affects cotreatment, increases expression, decreases methylation	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
terbufos	increases methylation	1
arsenite	increases methylation	1
afimoxifene	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
mercuric bromide	affects cotreatment, increases expression	1
1,1-bis(4-hydroxyphenyl)-2-phenylbut-1-ene	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Carbamazepine	affects expression	1
Copper	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1ST	NCC-aRMS1-C1	Cancer cell line	Male
CVCL_B8M3	Abcam HCT 116 PAX7 KO	Cancer cell line	Male
CVCL_B8ZZ	Abcam MCF-7 PAX7 KO	Cancer cell line	Female
CVCL_B9PA	Abcam A-549 PAX7 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT02567435	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma
NCT04994132	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Compare Early Use of Vinorelbine and Maintenance Therapy for Patients With High Risk Rhabdomyosarcoma
NCT06669013	PHASE3	RECRUITING	Chemo-immunotherapy in Patients Under 18 Years of Age With Bone and Soft Tissue Sarcomas
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT00923351	PHASE1/PHASE2	COMPLETED	Therapy to Treat Ewing’s Sarcoma, Rhabdomyosarcoma or Neuroblastoma
NCT05071209	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors
NCT01923701	Not specified	COMPLETED	Cognitive Behavioral Therapy for the Prevention of Paranoia in Adolescents at High Risk
NCT03296371	Not specified	ACTIVE_NOT_RECRUITING	Genetic Mutational Analysis of Saliva or Buccal Mucosa Samples From Patients With Embryonal or Alveolar Rhabdomyosarcoma
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents