MYF5

Summary

MYF5 (myogenic factor 5, HGNC:7565) is a protein-coding gene on chromosome 12q21.31, encoding Myogenic factor 5 (P13349). Transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to contribute to E-box binding activity. Predicted to be involved in several processes, including muscle cell fate commitment; positive regulation of cell differentiation; and skeletal muscle cell differentiation. Predicted to act upstream of or within several processes, including positive regulation of transcription by RNA polymerase II; skeletal system morphogenesis; and somitogenesis. Located in nucleoplasm.

Source: NCBI Gene 4617 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ophthalmoplegia, external, with rib and vertebral anomalies (Strong, GenCC)
• Clinical variants (ClinVar): 46 total — 2 pathogenic
• Phenotypes (HPO): 14
• Transcription factor: yes — 30 downstream targets (CollecTRI)
• MANE Select transcript: NM_005593

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7565
Approved symbol	MYF5
Name	myogenic factor 5
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Aliases	bHLHc2
Ensembl gene	ENSG00000111049
Ensembl biotype	protein_coding
OMIM	159990
Entrez	4617

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000228644

RefSeq mRNA: 1 — MANE Select: NM_005593 NM_005593

CCDS: CCDS9020

Canonical transcript exons

ENST00000228644 — 3 exons

Exon	Start	End
ENSE00000752674	80718358	80718433
ENSE00000875269	80716912	80717564
ENSE00000875270	80718861	80719671

Expression profiles

Bgee: expression breadth broad, 26 present calls, max score 72.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.4825 / max 1343.8781, expressed in 89 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127116	2.4825	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	72.42	silver quality
hindlimb stylopod muscle	UBERON:0004252	71.83	gold quality
gastrocnemius	UBERON:0001388	71.76	gold quality
muscle of leg	UBERON:0001383	71.23	gold quality
muscle organ	UBERON:0001630	70.33	gold quality
skeletal muscle tissue	UBERON:0001134	68.09	gold quality
deltoid	UBERON:0001476	67.52	silver quality
gluteal muscle	UBERON:0002000	65.61	silver quality
triceps brachii	UBERON:0001509	64.99	gold quality
diaphragm	UBERON:0001103	64.49	gold quality
tibialis anterior	UBERON:0001385	64.45	silver quality
muscle tissue	UBERON:0002385	63.64	gold quality
hair follicle	UBERON:0002073	62.80	gold quality
buccal mucosa cell	CL:0002336	60.49	gold quality
body of tongue	UBERON:0011876	59.07	silver quality
mucosa of urinary bladder	UBERON:0001259	56.97	gold quality
decidua	UBERON:0002450	56.55	gold quality
pancreatic ductal cell	CL:0002079	55.22	silver quality
lower lobe of lung	UBERON:0008949	54.07	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
epithelial cell of pancreas	CL:0000083	50.37	gold quality
lateral globus pallidus	UBERON:0002476	50.34	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
Brodmann (1909) area 46	UBERON:0006483	49.57	gold quality
thymus	UBERON:0002370	49.37	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-5	yes	437.37
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

30 targets.

Target	Regulation
ATP9A
ATP9B
CCND3
CDH15	Activation
CKM	Unknown
DES	Activation
EIF3K
FASTK
FGF4
FOXE1	Activation
GNAS
IGFBP5	Activation
MEF2A
MYCL	Activation
MYF5
MYF6
MYL4	Activation
MYOD1	Activation
MYOG	Activation
NEU1	Activation
PDGFA	Unknown
PRKACA
RHOA
RRAD
RUNX1	Activation
SHH
SP7	Activation
VGLL2
VGLL3	Activation
WNT2

JASPAR motifs

Motif	Name	Family
MA1641.1	MYF5	MyoD/ASC-related factors
MA1641.2	MYF5	MyoD/ASC-related factors

JASPAR matrix evidence (PMIDs): PMID:26906734

Upstream regulators (CollecTRI, top): CREB1, CTNNB1, GLI2, GLI3, LEF1, LHX2, MEOX2, MYF5, MYF6, MYOD1, MYOG, PAX3, PAX7, PITX2, SMAD2, SMAD3, SMAD4, SPI1, TEAD1, ZIC1

miRNA regulators (miRDB)

60 targeting MYF5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Literature-anchored findings (GeneRIF, showing 11)

• The myogenic basic helix-loop-helix family of transcription factors, MyoD, Myf5, myogenin, and MRF4, can each activate the muscle differentiation program. (PMID:12105204)
• Mrf4 expression precedes or is contemporaneous with that of Myf5, suggesting that this transcription factor plays a hitherto unsuspected role in myogenesis (PMID:12204280)
• Myogenin and myogenic differentiation factor D (MyoD) mRNAs increased (P < 0.05) in young and old, whereas myogenic factor (myf)-5 mRNA increased in young only (P < 0.05). Myf-6 protein increased (P < 0.05) in both young and old. (PMID:16614355)
• A novel homozygous polymorphism that prevented the binding of MYF-5 to FOXE1 promoter and affected the FOXE1 expression was found in 45% nonsyndromic cleft palate. (PMID:19192046)
• DUX4c induces the MYF5 protein and myoblast proliferation, and has a role in facioscapulohumeral muscular dystrophy (PMID:19829708)
• results are the first demonstration of a myogenic conversion of human mesenchymal and endothelial cells by Myf5 (PMID:21810080)
• Pitx2c expression is reactivated, while expression of Myf5 is downregulated in human systolic heart failure as determined by qRT-PCR and Western blot analyses. (PMID:24595098)
• Analysis of human rhabdomyosarcoma revealed that MYF5 and MYOD are mutually-exclusively expressed and each is required for sustained tumor growth. (PMID:28080960)
• SNAIL silencing allows the re-expression of MYF5 and canonical MYOD binding, promoting alveolar rhabdomyosarcoma cell myogenic differentiation. (PMID:29844345)
• The direct role of MYF5 in rib, spine, and extraocular muscle formation in humans. (PMID:29887215)
• Identification of a Novel Frameshift Variant in MYF5 Leading to External Ophthalmoplegia with Rib and Vertebral Anomalies. (PMID:38927634)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	myf5	ENSDARG00000007277
mus_musculus	Myf5	ENSMUSG00000000435
rattus_norvegicus	Myf5	ENSRNOG00000004768
drosophila_melanogaster	nau	FBGN0002922
caenorhabditis_elegans		WBGENE00001948

Paralogs (3): MYF6 (ENSG00000111046), MYOG (ENSG00000122180), MYOD1 (ENSG00000129152)

Protein

Protein identifiers

Myogenic factor 5 — P13349 (reviewed: P13349)

Alternative names: Class C basic helix-loop-helix protein 2

All UniProt accessions (1): P13349

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYOG and MYOD1, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein.

Subcellular location. Nucleus.

Disease relevance. Ophthalmoplegia, external, with rib and vertebral anomalies (EORVA) [MIM:618155] An autosomal recessive disorder characterized by congenital nonprogressive external ophthalmoplegia, ptosis, scoliosis, torticollis, and vertebral and rib anomalies. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_005584* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002546	MyoD_N	Domain
IPR011598	bHLH_dom	Domain
IPR022032	Myf5	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR039704	Myogenic_factor	Family

Pfam: PF00010, PF01586, PF12232

UniProt features (6 total): helix 2, chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7Z5K	X-RAY DIFFRACTION	2.28
7Z5I	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13349-F1	65.20	0.23

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-525793	Myogenesis
R-HSA-9839394	TGFBR3 expression
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9839373	Signaling by TGFBR3

MSigDB gene sets: 203 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_SKELETAL_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, MYOGENIN_Q6, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, PAX8_B

GO Biological Process (21): cartilage condensation (GO:0001502), ossification (GO:0001503), somitogenesis (GO:0001756), regulation of cell-matrix adhesion (GO:0001952), regulation of transcription by RNA polymerase II (GO:0006357), muscle organ development (GO:0007517), skeletal muscle tissue development (GO:0007519), extracellular matrix organization (GO:0030198), skeletal muscle cell differentiation (GO:0035914), muscle cell fate commitment (GO:0042693), camera-type eye development (GO:0043010), positive regulation of myoblast differentiation (GO:0045663), embryonic skeletal system morphogenesis (GO:0048704), positive regulation of skeletal muscle fiber development (GO:0048743), muscle tissue morphogenesis (GO:0060415), regulation of DNA-templated transcription (GO:0006355), tissue development (GO:0009888), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), animal organ development (GO:0048513), muscle organ morphogenesis (GO:0048644)

GO Molecular Function (8): 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 activator activity, RNA polymerase II-specific (GO:0001228), protein dimerization activity (GO:0046983), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), E-box binding (GO:0070888)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Developmental Biology	1
Signaling by TGFBR3	1
Signal Transduction	1
Signaling by TGFB family members	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
skeletal system morphogenesis	2
transcription by RNA polymerase II	2
anatomical structure development	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
cartilage development	1
cell aggregation	1
multicellular organismal process	1
anterior/posterior pattern specification	1
segmentation	1
chordate embryonic development	1
anatomical structure formation involved in morphogenesis	1
somite development	1
cell-matrix adhesion	1
regulation of cell-substrate adhesion	1
regulation of DNA-templated transcription	1
animal organ development	1
muscle structure development	1
striated muscle tissue development	1
skeletal muscle organ development	1
extracellular structure organization	1
external encapsulating structure organization	1
skeletal muscle tissue development	1
cell differentiation	1
muscle cell differentiation	1
cell fate commitment	1
eye development	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
embryonic organ morphogenesis	1
embryonic skeletal system development	1
positive regulation of cell development	1
positive regulation of skeletal muscle tissue development	1
skeletal muscle fiber development	1
regulation of skeletal muscle fiber development	1
positive regulation of striated muscle cell differentiation	1
muscle organ morphogenesis	1
tissue morphogenesis	1

Protein interactions and networks

STRING

1860 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYF5	PAX3	P23760	957
MYF5	PAX7	P23759	896
MYF5	MSTN	O14793	855
MYF5	MYF6	P23409	803
MYF5	SIX1	Q15475	803
MYF5	CDH15	P55291	795
MYF5	PRDM16	Q9HAZ2	792
MYF5	MEF2A	Q02078	772
MYF5	MEF2C	Q06413	762
MYF5	TCF3	P15883	748
MYF5	DACH1	Q9UI36	746
MYF5	IGF1	P01343	735
MYF5	MYH6	P13533	726
MYF5	MSC	O60682	712
MYF5	UCP1	P25874	705

IntAct

87 interactions, top by confidence:

A	B	Type	Score
MYF5	PACRGL	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ZNF417	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ENKD1	psi-mi:“MI:0915”(physical association)	0.560
MYF5	AQP1	psi-mi:“MI:0915”(physical association)	0.560
MYF5	FIGLA	psi-mi:“MI:0915”(physical association)	0.560
MYF5	NHLH2	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ZNF587	psi-mi:“MI:0915”(physical association)	0.560
MYF5	CCDC13	psi-mi:“MI:0915”(physical association)	0.560
MYF5	TLE5	psi-mi:“MI:0915”(physical association)	0.560
MYF5	FAM124B	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ID1	psi-mi:“MI:0915”(physical association)	0.560
MYF5	CHIC2	psi-mi:“MI:0915”(physical association)	0.560
MYF5	SCX	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	MYF5	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ZNF835	psi-mi:“MI:0915”(physical association)	0.560
MYF5	RARG	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ID3	psi-mi:“MI:0915”(physical association)	0.560
MYF5	C14orf119	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ITGB4	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ZNF575	psi-mi:“MI:0915”(physical association)	0.560
MYF5	PIN1	psi-mi:“MI:0915”(physical association)	0.560
MYF5	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
MYF5	SGF29	psi-mi:“MI:0915”(physical association)	0.560
SNAPC5	MYF5	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
MYF5	ZNF250	psi-mi:“MI:0915”(physical association)	0.560
PACRGL	MYF5	psi-mi:“MI:0915”(physical association)	0.000
ZNF417	MYF5	psi-mi:“MI:0915”(physical association)	0.000
ENKD1	MYF5	psi-mi:“MI:0915”(physical association)	0.000
AQP1	MYF5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): TCF3 (Reconstituted Complex), MYF5 (Two-hybrid), MYF5 (Two-hybrid), ID3 (Two-hybrid), FAM124B (Two-hybrid), ENKD1 (Two-hybrid), ID1 (Two-hybrid), PIN1 (Two-hybrid), ZNF835 (Two-hybrid), ITGB4 (Two-hybrid), MSGN1 (Two-hybrid), PACRGL (Two-hybrid), ANKRD11 (Two-hybrid), RARG (Two-hybrid), ZNF417 (Two-hybrid)

ESM2 similar proteins: A0A1R3RGK4, A2R6G8, A2T713, A2T7L8, A4IFU7, F1QDF8, G1X9A9, G5EG44, I1S491, O14948, O42202, O42261, O42342, O75030, O88368, O93507, P01103, P06876, P13349, P13904, P16075, P16076, P17667, P19484, P21572, P46200, P70284, P79766, P80073, Q01663, Q08759, Q08874, Q13562, Q16534, Q22835, Q28GD5, Q5XFQ6, Q60430, Q63302, Q64709

Diamond homologs: B6VQA1, M0QWB7, O13125, O13126, O35885, O42202, O57598, O96004, P09774, P09775, P10083, P10084, P10085, P13349, P15172, P15375, P17667, P19335, P19359, P19360, P22816, P23409, P24699, P29331, P34061, P34555, P46581, P48987, P49811, P50553, P57100, P57101, P57102, P59101, P61295, P61296, P70447, P70562, P70595, P70660

SIGNOR signaling

25 interactions.

A	Effect	B	Mechanism
LEF1	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
TEAD1	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
SHH	up-regulates	MYF5
“PAX7/MLL1 complex”	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
“PAX7/MLL2 complex”	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
PAX3	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
MYF5	up-regulates	Skeletal_muscle_differentiation
WNT4	up-regulates	MYF5
WNT6	up-regulates	MYF5
WNT1	“up-regulates activity”	MYF5
MDFI	“down-regulates activity”	MYF5	binding
MYF5	“up-regulates quantity by expression”	DES	“transcriptional regulation”
PAX7	“up-regulates quantity by expression”	MYF5	“transcriptional regulation”
MYF5	“up-regulates quantity”	mir-206	“transcriptional regulation”
MYF5	“up-regulates quantity”	MIR1-1	“transcriptional regulation”
WNT5A	“up-regulates activity”	MYF5
CSNK2A1	“up-regulates activity”	MYF5	phosphorylation
CSNK2A2	“up-regulates activity”	MYF5	phosphorylation
MYF5	“up-regulates activity”	Proliferation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	39
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
523662	NM_005593.3(MYF5):c.283C>T (p.Arg95Cys)	Pathogenic
523663	NM_005593.3(MYF5):c.23_32del (p.Gln8fs)	Pathogenic

SpliceAI

167 predictions. Top by Δscore:

Variant	Effect	Δscore
12:80717560:GCATG:G	donor_gain	1.0000
12:80717563:TGG:T	donor_loss	1.0000
12:80717564:GGT:G	donor_loss	1.0000
12:80717565:G:GG	donor_gain	1.0000
12:80717565:GTA:G	donor_loss	1.0000
12:80717566:T:G	donor_loss	1.0000
12:80718356:A:AG	acceptor_gain	1.0000
12:80718357:G:GG	acceptor_gain	1.0000
12:80718357:GCCC:G	acceptor_gain	1.0000
12:80717563:TG:T	donor_gain	0.9900
12:80717564:GG:G	donor_gain	0.9900
12:80718859:A:AG	acceptor_gain	0.9900
12:80718860:G:GG	acceptor_gain	0.9900
12:80717561:CATG:C	donor_gain	0.9800
12:80718429:AAATG:A	donor_loss	0.9800
12:80718430:AATGG:A	donor_loss	0.9800
12:80718431:ATGG:A	donor_loss	0.9800
12:80718432:TGGT:T	donor_loss	0.9800
12:80718433:GGTAA:G	donor_loss	0.9800
12:80718434:GTAAG:G	donor_loss	0.9800
12:80718435:TA:T	donor_loss	0.9800
12:80718436:AA:A	donor_loss	0.9800
12:80718860:GTAT:G	acceptor_gain	0.9800
12:80717562:ATG:A	donor_gain	0.9700
12:80718860:GT:G	acceptor_gain	0.9700
12:80718343:T:TA	acceptor_loss	0.9600
12:80718348:T:A	acceptor_loss	0.9600
12:80718352:TTATA:T	acceptor_loss	0.9600
12:80718353:TATA:T	acceptor_loss	0.9600
12:80718354:ATAGC:A	acceptor_loss	0.9600

AlphaMissense

1672 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:80717271:T:A	W70R	1.000
12:80717271:T:C	W70R	1.000
12:80717273:G:C	W70C	1.000
12:80717273:G:T	W70C	1.000
12:80717326:C:A	A88D	1.000
12:80717334:C:A	R91S	1.000
12:80717337:G:A	E92K	1.000
12:80717338:A:T	E92V	1.000
12:80717339:G:C	E92D	1.000
12:80717339:G:T	E92D	1.000
12:80717346:C:A	R95S	1.000
12:80717350:T:C	L96P	1.000
12:80717370:T:C	F103L	1.000
12:80717371:T:C	F103S	1.000
12:80717371:T:G	F103C	1.000
12:80717372:C:A	F103L	1.000
12:80717372:C:G	F103L	1.000
12:80717380:T:A	L106H	1.000
12:80717380:T:C	L106P	1.000
12:80717423:G:C	K120N	1.000
12:80717423:G:T	K120N	1.000
12:80717434:T:A	L124H	1.000
12:80717434:T:C	L124P	1.000
12:80717442:G:C	A127P	1.000
12:80717464:T:C	L134P	1.000
12:80717262:T:A	C67S	0.999
12:80717262:T:C	C67R	0.999
12:80717263:G:C	C67S	0.999
12:80717264:C:G	C67W	0.999
12:80717277:T:A	C72S	0.999

dbSNP variants (sampled 300 via entrez): RS1000220856 (12:80717933 A>G), RS1001023640 (12:80716195 C>G), RS1001122658 (12:80718620 C>G), RS1001234291 (12:80718802 A>G), RS1002098060 (12:80717963 A>C), RS1002698949 (12:80719383 T>C), RS1002794671 (12:80719981 C>T), RS1005148475 (12:80715140 T>A), RS1005352337 (12:80718177 A>G), RS1006412241 (12:80716680 C>G,T), RS1006597086 (12:80715934 C>T), RS1007079651 (12:80719305 A>G), RS1007441058 (12:80717541 A>G), RS1008010389 (12:80717215 A>G), RS1008856362 (12:80718809 C>A,G,T)

Disease associations

OMIM: gene MIM:159990 | disease phenotypes: MIM:618155

GenCC curated gene-disease

Disease	Classification	Inheritance
ophthalmoplegia, external, with rib and vertebral anomalies	Strong	Autosomal recessive

Mondo (2): ophthalmoplegia, external, with rib and vertebral anomalies (MONDO:0032565), scoliosis (MONDO:0005392)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000473	Torticollis
HP:0000508	Ptosis
HP:0000544	External ophthalmoplegia
HP:0000577	Exotropia
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000773	Short ribs
HP:0000921	Missing ribs
HP:0002650	Scoliosis
HP:0003577	Congenital onset
HP:0005864	Pseudoarthrosis
HP:0012366	Basilar invagination
HP:0025584	Hypotropia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012600	Scoliosis	C05.116.900.800.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	2
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Amiloride	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4I2	SEES3-1V human MYF5, clone1	Embryonic stem cell	Male
CVCL_A4I3	SEES3-1V human MYF5, clone2	Embryonic stem cell	Male
CVCL_A4I4	SEES3-1V human MYF5, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00508066	PHASE4	COMPLETED	Continuous Local Infusion of Anesthetic at the Incisional Site for Scoliosis Surgery
NCT00510575	PHASE4	COMPLETED	Surgical Outcomes Using Variable Rod Diameters in the Treatment of Idiopathic Scoliosis
NCT00768313	PHASE4	WITHDRAWN	Phase IV Comparing Rods of Yield Strengths to Correct Adolescent Idiopathic Scoliosis.
NCT00880607	PHASE4	COMPLETED	Intrathecal Morphine Versus Epidural Extended Release Morphine for Pediatric Patients Undergoing Spinal Fusion
NCT00958581	PHASE4	COMPLETED	Tranexamic Acid (TXA) Versus Epsilon Aminocaproic Acid (EACA) Versus Placebo for Spine Surgery
NCT01852747	PHASE4	TERMINATED	Comparison of Actifuse ABX and Local Bone in Spinal Surgery
NCT02464813	PHASE4	COMPLETED	Effect of Pregabalin on Immediate Post-operative and Longterm Pain
NCT02465099	PHASE4	TERMINATED	Posterior Spinal Fusion With Two Energy Dissection Techniques
NCT06540885	PHASE4	RECRUITING	A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery
NCT06616220	PHASE4	COMPLETED	Dexamethasone for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT06789016	PHASE4	COMPLETED	Dexmedetomidine for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT00323752	PHASE3	COMPLETED	Recombinant Human Erythropoietin Compared to Autologous Pre-Donation Prior to Scoliosis Surgery in Children.
NCT00684112	PHASE3	COMPLETED	Analgesic Effects of Gabapentin After Scoliosis Surgery in Children
NCT00737997	PHASE3	COMPLETED	Effect of Early Morphine Administration on the Development of Acute Opioid Tolerance During Pediatric Scoliosis Surgery
NCT01103115	PHASE3	COMPLETED	Calcium + Vitamin D Supplementation for Low Bone Mass in Adolescent Idiopathic Scoliosis (AIS)
NCT01108211	PHASE3	COMPLETED	Improving Low Bone Mass With Vibration Therapy in Adolescent Idiopathic Scoliosis (AIS)
NCT01205256	PHASE3	COMPLETED	IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction
NCT02558010	PHASE3	COMPLETED	Perioperative Methadone Use to Decrease Opioid Requirement in Pediatric Spinal Fusion Patients
NCT03537612	PHASE3	TERMINATED	Sensorial and Physiological Mechanism-based Assessments of Perioperative Pain
NCT00273598	PHASE2	COMPLETED	Comparing Two Instrumentation Systems for the Treatment of Adolescent Scoliosis
NCT01148888	PHASE2	COMPLETED	The Effect of Magnesium Sulfate on Motor and Somatosensory Evoked Potentials in Children Undergoing Scoliosis Surgery
NCT00154505	PHASE1	COMPLETED	Effects of Lateral Trunk Support on Spinal Alignment in Spinal Cord Injured Persons
NCT00155545	PHASE1	COMPLETED	Influence of Leg Length Discrepancy on the Spinal Shape and Biomechanics in Functional and Idiopathic Scoliosis Patients
NCT00671931	PHASE1	COMPLETED	Susceptibility of Motor-Evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine
NCT01677650	PHASE1	WITHDRAWN	Pharmacogenomics of Methadone in Spine Fusion Surgery
NCT00207857	Not specified	WITHDRAWN	Test-Retest Reliability of Pulmonary Function Tests in Patients With Duchenne’s Muscular Dystrophy
NCT00256672	Not specified	UNKNOWN	Effectiveness of Bracing in Preventing Scoliosis in Children With Spinal Cord Injury
NCT00320619	Not specified	COMPLETED	Epsilon-Aminocaproaic Acid to Reduce the Need for Blood Transfusions During and Following Spine Surgery
NCT00411060	Not specified	RECRUITING	Clinical Orthopaedic Data Bank (Acute and Chronic)
NCT00445393	Not specified	COMPLETED	Adolescent Idiopathic Scoliosis and Mental Health
NCT00577226	Not specified	TERMINATED	Shilla Growth Permitting Spinal Instrumentation System for Treatment of Scoliosis in the Immature Spine
NCT00680264	Not specified	UNKNOWN	Prospective Database Registry Study of Scoliosis in Children With Cerebral Palsy
NCT00726128	Not specified	COMPLETED	Patient Outcomes Evaluation of the EBI Vuelock™ Anterior Cervical Plate System
NCT00842218	Not specified	UNKNOWN	The Idiopathic Scoliosis and Its Treatment (Orthopaedic and Surgery): Effect of the Severity, the Orthosis and the Arthrodesis on the Gait
NCT00854828	Not specified	COMPLETED	A Multicenter Prospective Study of Quality of Life in Adult Scoliosis
NCT00890227	Not specified	COMPLETED	Incidence of Proximal Junctional Kyphosis (PJK) in Long Posterior Spinal Fusion: A Study Comparing Traditional Open Surgery to Minimally Invasive Percutaneous Technique at the Proximal Fusion Levels
NCT00958542	Not specified	SUSPENDED	Prospective Study of Cerebral Palsy Scoliosis
NCT00994656	Not specified	COMPLETED	Is Pleth Variability Index (PVI) a Surrogate for Pulse Pressure Variations (PPV) in Pediatric Spine Fusion (SF) Surgery?
NCT01087034	Not specified	COMPLETED	Bracing During Infantile Scoliosis: Airways Study
NCT01109082	Not specified	COMPLETED	Gait and Postural Stability Assessment in Children With Idiopathic Scoliosis Undergoing Posterior Spine Instrumentation