MYOZ3

Summary

MYOZ3 (myozenin 3, HGNC:18565) is a protein-coding gene on chromosome 5q33.1, encoding Myozenin-3 (Q8TDC0). Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere.

The protein encoded by this gene is specifically expressed in the skeletal muscle, and belongs to the myozenin family. Members of this family function as calcineurin-interacting proteins that help tether calcineurin to the sarcomere of cardiac and skeletal muscle. They play an important role in modulation of calcineurin signaling.

Source: NCBI Gene 91977 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_001122853

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18565
Approved symbol	MYOZ3
Name	myozenin 3
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	CS-3, CS3, FRP3, FATZ-3
Ensembl gene	ENSG00000164591
Ensembl biotype	protein_coding
OMIM	610735
Entrez	91977

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297130, ENST00000456566, ENST00000517768, ENST00000517861, ENST00000520112, ENST00000521300, ENST00000523553, ENST00000524256, ENST00000615557, ENST00000873985, ENST00000916726, ENST00000948707

RefSeq mRNA: 2 — MANE Select: NM_001122853 NM_001122853, NM_133371

CCDS: CCDS4309

Canonical transcript exons

ENST00000517768 — 7 exons

Exon	Start	End
ENSE00001085697	150670484	150670638
ENSE00001085698	150671597	150671650
ENSE00001761452	150661251	150661427
ENSE00002092205	150676707	150679368
ENSE00003490636	150671755	150671908
ENSE00003562639	150662941	150663002
ENSE00003590509	150672340	150672502

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 97.82.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9650 / max 168.3860, expressed in 219 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59513	0.2647	27
59510	0.1858	24
59516	0.1844	110
203743	0.1085	51
59508	0.0862	28
59509	0.0524	20
59511	0.0383	13
59512	0.0274	12
59514	0.0174	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.82	gold quality
vastus lateralis	UBERON:0001379	97.31	gold quality
quadriceps femoris	UBERON:0001377	96.82	gold quality
diaphragm	UBERON:0001103	96.80	gold quality
biceps brachii	UBERON:0001507	96.76	gold quality
gluteal muscle	UBERON:0002000	96.69	gold quality
body of tongue	UBERON:0011876	96.51	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.04	gold quality
skeletal muscle tissue	UBERON:0001134	95.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.66	gold quality
triceps brachii	UBERON:0001509	94.51	gold quality
deltoid	UBERON:0001476	92.72	gold quality
muscle organ	UBERON:0001630	92.58	gold quality
skeletal muscle organ	UBERON:0014892	92.58	gold quality
muscle tissue	UBERON:0002385	91.29	gold quality
muscle of leg	UBERON:0001383	91.05	gold quality
gastrocnemius	UBERON:0001388	90.64	gold quality
tongue	UBERON:0001723	90.04	gold quality
tibialis anterior	UBERON:0001385	89.00	silver quality
buccal mucosa cell	CL:0002336	88.50	gold quality
type B pancreatic cell	CL:0000169	84.68	gold quality
olfactory bulb	UBERON:0002264	84.34	gold quality
tibia	UBERON:0000979	83.71	gold quality
superior surface of tongue	UBERON:0007371	83.45	gold quality
pharyngeal mucosa	UBERON:0000355	80.90	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	80.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.00	gold quality
tendon of biceps brachii	UBERON:0008188	77.04	silver quality
apex of heart	UBERON:0002098	76.78	gold quality
tendon	UBERON:0000043	75.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting MYOZ3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615

Literature-anchored findings (GeneRIF, showing 1)

• Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins. (PMID:11842093)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	myoz3a	ENSDARG00000067701
danio_rerio		ENSDARG00000104924
mus_musculus	Myoz3	ENSMUSG00000049173
rattus_norvegicus	Myoz3	ENSRNOG00000087346

Paralogs (2): MYOZ2 (ENSG00000172399), MYOZ1 (ENSG00000177791)

Protein

Protein identifiers

Myozenin-3 — Q8TDC0 (reviewed: Q8TDC0)

Alternative names: Calsarcin-3, FATZ-related protein 3

All UniProt accessions (3): E5RII7, Q8TDC0, H0YC50

UniProt curated annotations — full annotation on UniProt →

Function. Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma-filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis.

Subunit / interactions. Interacts with ACTN2, LDB3, FLNC, PPP3CA and TCAP.

Subcellular location. Cytoplasm. Myofibril. Sarcomere. Z line.

Tissue specificity. Expressed specifically in skeletal muscle. Not detected in heart.

Similarity. Belongs to the myozenin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TDC0-1	1	yes
Q8TDC0-2	2
Q8TDC0-3	3

RefSeq proteins (2): NP_001116325, NP_588612 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008438	MYOZ	Family

Pfam: PF05556

UniProt features (12 total): region of interest 4, splice variant 4, sequence variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDC0-F1	61.56	0.02

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 (1): 31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_FLT1, WWTAAGGC_UNKNOWN, GCANCTGNY_MYOD_Q6, CAGCTG_AP4_Q5, MORF_RAD51L3, MODULE_118, BROWNE_HCMV_INFECTION_24HR_UP, MODULE_379, MYOD_Q6, GOMF_ACTIN_BINDING, E12_Q6, MODULE_242, GOCC_I_BAND, MODULE_104

GO Biological Process (0):

GO Molecular Function (4): actin binding (GO:0003779), telethonin binding (GO:0031433), FATZ binding (GO:0051373), protein binding (GO:0005515)

GO Cellular Component (3): actin cytoskeleton (GO:0015629), Z disc (GO:0030018), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeletal protein binding	3
cellular anatomical structure	2
binding	1
cytoskeleton	1
I band	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYOZ3	LDB3	O75112	871
MYOZ3	ACTN2	P35609	790
MYOZ3	TCAP	O15273	784
MYOZ3	FLNC	Q14315	761
MYOZ3	ACTN1	P12814	700
MYOZ3	MYOT	Q9UBF9	627
MYOZ3	MYH4	Q9Y623	526
MYOZ3	ZNF780A	O75290	519
MYOZ3	CALML6	Q8TD86	509
MYOZ3	CALML4	Q96GE6	509
MYOZ3	CALML5	Q9NZT1	509
MYOZ3	CALML3	P27482	508
MYOZ3	TNNC2	P02585	491
MYOZ3	CALM1	P02593	486
MYOZ3	GRTP1	Q5TC63	475

IntAct

311 interactions, top by confidence:

A	B	Type	Score
KRT75	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
MYOZ3	ZNF620	psi-mi:“MI:0915”(physical association)	0.560
MYO15B	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
MYOZ3	GOLGA6A	psi-mi:“MI:0915”(physical association)	0.560
KANK2	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
RINT1	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
FHL3	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
ASPG	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP8-1	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
UFSP1	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
CIMIP2B	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
LMO2	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
FAM168B	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
BCAS2	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
C10orf55	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
MYOZ3	TBX15	psi-mi:“MI:0915”(physical association)	0.560
KRT36	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
PTK6	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-6	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
MYOZ3	SPMIP5	psi-mi:“MI:0915”(physical association)	0.560
CREM	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
LONRF1	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
DAZAP2	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC6A	MYOZ3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (69): MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid), MYOZ3 (Two-hybrid)

ESM2 similar proteins: A4IG59, A4QNR8, A7Z063, A8K0Z3, B2RYF7, B5DEB9, C4AMC7, D4A702, O48713, O54880, O70279, P70302, P84903, Q13586, Q1LYM3, Q28DN4, Q32N92, Q3UB74, Q3UIW5, Q3YBR2, Q4PS85, Q4V7K4, Q561X3, Q58CP9, Q5E9V3, Q5R6I2, Q5U4A3, Q5XI59, Q5ZKA6, Q659C4, Q68FU8, Q6DD45, Q6PKG0, Q6VEQ5, Q6ZQ58, Q8BWB1, Q8CH02, Q8IWZ8, Q8R4E4, Q8SQ24

Diamond homologs: Q4PS85, Q5E9V3, Q5R6I2, Q8R4E4, Q8SQ24, Q8TDC0, Q9JJW5, Q9JK37, Q9NP98, Q9NPC6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	7	12.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1158 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150670478:T:TA	acceptor_gain	1.0000
5:150670482:A:AG	acceptor_gain	1.0000
5:150670483:G:GA	acceptor_gain	1.0000
5:150670483:GTCCC:G	acceptor_gain	1.0000
5:150670634:GGGCG:G	donor_gain	1.0000
5:150670635:GGCG:G	donor_gain	1.0000
5:150670635:GGCGG:G	donor_gain	1.0000
5:150670636:GCG:G	donor_gain	1.0000
5:150670636:GCGG:G	donor_gain	1.0000
5:150670639:G:GG	donor_gain	1.0000
5:150670643:G:GG	donor_gain	1.0000
5:150671664:G:T	donor_gain	1.0000
5:150671680:G:T	donor_gain	1.0000
5:150672331:C:CA	acceptor_gain	1.0000
5:150672336:CTAG:C	acceptor_loss	1.0000
5:150672337:TA:T	acceptor_loss	1.0000
5:150672338:AGG:A	acceptor_loss	1.0000
5:150672339:G:GT	acceptor_loss	1.0000
5:150672499:ACAA:A	donor_gain	1.0000
5:150672499:ACAAG:A	donor_loss	1.0000
5:150672500:CAAGT:C	donor_loss	1.0000
5:150672502:AGTAA:A	donor_loss	1.0000
5:150672503:G:GG	donor_gain	1.0000
5:150672503:GTAA:G	donor_loss	1.0000
5:150672504:T:A	donor_loss	1.0000
5:150661075:TCCAG:T	donor_loss	0.9900
5:150661076:CCAG:C	donor_loss	0.9900
5:150661079:G:GA	donor_loss	0.9900
5:150661080:GT:G	donor_loss	0.9900
5:150661081:T:G	donor_loss	0.9900

AlphaMissense

1621 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150670576:T:C	F52L	0.982
5:150670578:C:A	F52L	0.982
5:150670578:C:G	F52L	0.982
5:150670606:T:C	F62L	0.982
5:150670608:C:A	F62L	0.982
5:150670608:C:G	F62L	0.982
5:150676819:T:C	F234L	0.980
5:150676821:C:A	F234L	0.980
5:150676821:C:G	F234L	0.980
5:150670587:G:C	R55S	0.975
5:150670587:G:T	R55S	0.975
5:150676840:T:A	W241R	0.971
5:150676840:T:C	W241R	0.971
5:150676842:G:C	W241C	0.969
5:150676842:G:T	W241C	0.969
5:150672378:T:C	F155L	0.967
5:150672380:C:A	F155L	0.967
5:150672380:C:G	F155L	0.967
5:150676720:T:C	F201L	0.966
5:150676722:T:A	F201L	0.966
5:150676722:T:G	F201L	0.966
5:150672495:T:C	F194L	0.959
5:150672497:C:A	F194L	0.959
5:150672497:C:G	F194L	0.959
5:150670586:G:C	R55T	0.953
5:150670594:C:A	R58S	0.953
5:150670533:G:A	M37I	0.950
5:150670533:G:C	M37I	0.950
5:150670533:G:T	M37I	0.950
5:150670577:T:C	F52S	0.949

dbSNP variants (sampled 300 via entrez): RS1000024566 (5:150670317 T>A), RS1000160839 (5:150676439 G>A), RS1000198252 (5:150665083 G>A), RS1000271841 (5:150664804 A>G), RS1000452558 (5:150658902 C>T), RS1000750051 (5:150665983 C>T), RS1001130189 (5:150678168 G>A), RS1001150434 (5:150659417 G>A), RS1001195105 (5:150673969 G>A), RS1001340440 (5:150667746 T>A), RS1001431939 (5:150672042 C>A,T), RS1001456552 (5:150669210 G>A,C,T), RS1001487267 (5:150662664 G>T), RS1001630861 (5:150668981 A>G), RS1001821551 (5:150667466 A>G)

Disease associations

OMIM: gene MIM:610735 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19
GCST005855_1	Cholangiocarcinoma in primary sclerosing cholangitis	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
beta-methylcholine	affects expression	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	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Fenfluramine	decreases expression	1
Folic Acid	decreases expression	1
Pesticides	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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