CSRP3

cysteine and glycine rich protein 3, the group of LIM domain containing

Basic information

Region (hg38): 11:19182030-19210571

Links

ENSG00000129170 ∙ NCBI:8048 ∙ OMIM:600824 ∙ HGNC:2472 ∙ Uniprot:P50461 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 12 (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy 12 (Moderate), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1M (Limited), mode of inheritance: AD
• dilated cardiomyopathy 1M (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 12 (Strong), mode of inheritance: AD
• hypertrophic cardiomyopathy (Definitive), mode of inheritance: Semidominant
• hypertrophic cardiomyopathy (Moderate), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic 12; Cardiomyopathy, dilated, 1M	AD	Cardiovascular	Surveillance for manifestations (including with electrocardiogram and echocardiogram), including in asymptomatic individuals, is recommended; For individuals with cardiomyopathy, treatment such as medical therapy, pacemakers, and ICD can decrease morbidity and mortality, and early recognition and treatment can improve outcomes, though some individuals with progressive/refractory disease may require cardiac transplantation	Cardiovascular; Musculoskeletal	12507422; 14567970; 12642359; 18505755; 20087448; 22429680
There is a wide range of age at presentation

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CSRP3 gene.

• Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M (5 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSRP3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	68	1	75
missense		1	184	1		186
nonsense	4	1	2			7
start loss		1	1			2
frameshift	2		19			21
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3	2			5
splice region			11	8		19
non coding			22	37	19	78
Total	6	6	237	106	20

Highest pathogenic variant AF is 0.00000657

Variants in CSRP3

This is a list of pathogenic ClinVar variants found in the CSRP3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-19182032-A-G		Hypertrophic cardiomyopathy 12 • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Aug 26, 2021)
11-19182041-A-G		Hypertrophic cardiomyopathy 12	Benign (Jan 13, 2018)
11-19182095-A-G		Hypertrophic cardiomyopathy 12 • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Oct 04, 2021)
11-19182111-C-T		Hypertrophic cardiomyopathy 12 • Dilated cardiomyopathy 1M;Hypertrophic cardiomyopathy 12	Uncertain significance (Sep 17, 2021)
11-19182166-T-C		Hypertrophic cardiomyopathy 12	Uncertain significance (Jan 13, 2018)
11-19182220-A-C		Hypertrophic cardiomyopathy 12	Likely benign (Jan 13, 2018)
11-19182255-T-C		Hypertrophic cardiomyopathy 12 • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Aug 26, 2021)
11-19182378-T-A		Hypertrophic cardiomyopathy 12	Uncertain significance (Jan 12, 2018)
11-19182425-A-G		Hypertrophic cardiomyopathy 12 • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Sep 01, 2021)
11-19182496-A-G			Likely benign (Jul 11, 2018)
11-19182511-G-A		Hypertrophic cardiomyopathy 12 • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Jul 07, 2021)
11-19182658-C-T		not specified • Cardiomyopathy • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Benign/Likely benign (Aug 16, 2021)
11-19182672-A-G		Hypertrophic cardiomyopathy 12	Uncertain significance (Apr 06, 2022)
11-19182672-A-T		CSRP3-related disorder • Cardiovascular phenotype • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Jan 05, 2024)
11-19182672-ATTCT-A		not specified • Hypertrophic cardiomyopathy	Uncertain significance (Nov 05, 2023)
11-19182673-T-C		Cardiovascular phenotype	Likely benign (Feb 10, 2020)
11-19182675-C-G		Cardiovascular phenotype • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Mar 27, 2023)
11-19182679-C-G		Dilated cardiomyopathy 1M;Hypertrophic cardiomyopathy 12 • Cardiovascular phenotype	Uncertain significance (Nov 14, 2023)
11-19182679-CT-C		Cardiovascular phenotype	Uncertain significance (Jul 10, 2017)
11-19182683-T-A		Cardiovascular phenotype	Uncertain significance (Jun 09, 2022)
11-19182687-C-A		Primary familial hypertrophic cardiomyopathy • Cardiomyopathy • Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Mar 18, 2024)
11-19182687-CTTG-C		Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (Aug 13, 2021)
11-19182693-G-C		Dilated cardiomyopathy 1M;Hypertrophic cardiomyopathy 12	Uncertain significance (Sep 08, 2021)
11-19182702-C-T		Hypertrophic cardiomyopathy 12;Dilated cardiomyopathy 1M	Uncertain significance (May 28, 2022)
11-19182704-C-T		Cardiovascular phenotype	Uncertain significance (Oct 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSRP3	protein_coding	protein_coding	ENST00000533783	5	28543

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000159	0.692	125715	0	33	125748	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.139	115	111	1.04	0.00000705	1263
Missense in Polyphen		49	52.914	0.92603		620
Synonymous	-1.66	58	44.0	1.32	0.00000324	361
Loss of Function	0.881	7	10.0	0.699	5.04e-7	131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000521	0.000521
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Positive regulator of myogenesis. Acts as cofactor for myogenic bHLH transcription factors such as MYOD1, and probably MYOG and MYF6. Enhances the DNA-binding activity of the MYOD1:TCF3 isoform E47 complex and may promote formation of a functional MYOD1:TCF3 isoform E47:MEF2A complex involved in myogenesis (By similarity). Plays a crucial and specific role in the organization of cytosolic structures in cardiomyocytes. Could play a role in mechanical stretch sensing. May be a scaffold protein that promotes the assembly of interacting proteins at Z-line structures. It is essential for calcineurin anchorage to the Z line. Required for stress-induced calcineurin-NFAT activation (By similarity). The role in regulation of cytoskeleton dynamics by association with CFL2 is reported conflictingly: Shown to enhance CFL2-mediated F-actin depolymerization dependent on the CSRP3:CFL2 molecular ratio, and also shown to reduce the ability of CLF1 and CFL2 to enhance actin depolymerization (PubMed:19752190, PubMed:24934443). Proposed to contribute to the maintenance of muscle cell integerity through an actin-based mechanism. Can directly bind to actin filaments, cross-link actin filaments into bundles without polarity selectivity and protect them from dilution- and cofilin-mediated depolymerization; the function seems to involve its self-association (PubMed:24934443). In vitro can inhibit PKC/PRKCA activity (PubMed:27353086). Proposed to be involved in cardiac stress signaling by down-regulating excessive PKC/PRKCA signaling (By similarity). {ECO:0000250|UniProtKB:P50462, ECO:0000250|UniProtKB:P50463, ECO:0000269|PubMed:19752190, ECO:0000269|PubMed:24934443, ECO:0000269|PubMed:27353086}.
• Disease: DISEASE: Cardiomyopathy, dilated 1M (CMD1M) [MIM:607482]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:12507422, ECO:0000269|PubMed:18505755, ECO:0000269|PubMed:19412328}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 12 (CMH12) [MIM:612124]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:12642359, ECO:0000269|PubMed:15205937, ECO:0000269|PubMed:18505755, ECO:0000269|PubMed:27353086}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.217

Intolerance Scores

• loftool: 0.339
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.93

Haploinsufficiency Scores

• pHI: 0.430
• hipred: Y
• hipred_score: 0.579
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.687

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Csrp3
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: csrp3
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of the force of heart contraction;cardiac muscle hypertrophy;cellular calcium ion homeostasis;skeletal muscle tissue development;protein localization to organelle;detection of muscle stretch;positive regulation of transcription by RNA polymerase II;cardiac muscle tissue development;cardiac myofibril assembly;cardiac muscle contraction
• Cellular component: nucleus;cytoskeleton;Z disc
• Molecular function: actin binding;protein binding;structural constituent of muscle;telethonin binding;identical protein binding;actinin binding;metal ion binding