LDB3

LIM domain binding 3, the group of LIM domain containing|PDZ domain containing

Basic information

Region (hg38): 10:86666785-86736072

Previous symbols: [ "CMD1C" ]

Links

ENSG00000122367 ∙ NCBI:11155 ∙ OMIM:605906 ∙ HGNC:15710 ∙ Uniprot:O75112 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myofibrillar myopathy 4 (Moderate), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• myofibrillar myopathy 4 (Limited), mode of inheritance: AD
• myofibrillar myopathy 4 (Strong), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD
• arrhythmogenic right ventricular cardiomyopathy (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated 1C, with or without ventricular noncompaction; Myopathy, myofibrillar 4	AD	Cardiovascular	Individuals may have cardiovascular manifestations including dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow detection and early medical treatment, which may be beneficial to help decrease morbidity; In myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy	Cardiovascular; Musculoskeletal	14662268; 14660611; 15668942; 16427346; 17337483; 20627570; 20809097
LVNC may present early, while other cardiac manifestations may not present until much later

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LDB3 gene.

• Myofibrillar myopathy 4 (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LDB3 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			23	233	13	269
missense		1	550	38	4	593
nonsense			15	1		16
start loss						0
frameshift	4		22			26
inframe indel			11	1	1	13
splice donor/acceptor (+/-2bp)			11			11
splice region			26	18		44
non coding			50	108	65	223
Total	4	1	682	381	83

Variants in LDB3

This is a list of pathogenic ClinVar variants found in the LDB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-86666837-G-T			Likely benign (Sep 01, 2023)
10-86668279-A-G			Likely benign (Jun 14, 2018)
10-86668290-G-A			Benign (Jun 19, 2018)
10-86668319-A-T			Benign (Jun 14, 2018)
10-86668401-T-C			Benign (Jun 14, 2018)
10-86668410-G-T			Benign (Jun 14, 2018)
10-86668545-C-T		not specified	Benign (Apr 13, 2015)
10-86668546-G-A		not specified	Benign (Aug 08, 2011)
10-86668546-G-T		not specified	Likely benign (Apr 06, 2017)
10-86668558-A-G		not specified	Benign (Aug 02, 2012)
10-86668575-G-C			Uncertain significance (Aug 20, 2019)
10-86668578-T-C		not specified • Dilated cardiomyopathy 1C • Myofibrillar myopathy 4 • Left ventricular noncompaction cardiomyopathy • Myofibrillar Myopathy, Dominant	Benign/Likely benign (Aug 19, 2021)
10-86668588-G-A		not specified	Likely benign (Jul 08, 2016)
10-86668611-G-A		Myofibrillar Myopathy, Dominant • Myofibrillar myopathy 4 • Left ventricular noncompaction cardiomyopathy • Dilated cardiomyopathy 1C • Myofibrillar myopathy 4;Dilated cardiomyopathy 1C	Uncertain significance (Sep 27, 2021)
10-86668637-C-A		Myofibrillar myopathy 4 • Left ventricular noncompaction cardiomyopathy • Dilated Cardiomyopathy, Dominant • Myofibrillar Myopathy, Dominant	Conflicting classifications of pathogenicity (Jan 01, 2023)
10-86668649-T-C			Likely benign (Dec 03, 2018)
10-86668672-C-T		Dilated cardiomyopathy 1C • Dilated cardiomyopathy 1C;Myofibrillar myopathy 4	Uncertain significance (Aug 11, 2021)
10-86668673-G-A		not specified	Likely benign (Apr 22, 2016)
10-86668674-G-A		not specified	Likely benign (Sep 06, 2016)
10-86668676-C-T		not specified	Benign (Feb 20, 2023)
10-86668677-G-A		not specified	Conflicting classifications of pathogenicity (May 20, 2015)
10-86668689-A-G		Cardiovascular phenotype	Uncertain significance (Jun 04, 2024)
10-86668690-G-A			Uncertain significance (Feb 06, 2021)
10-86668691-C-A		Cardiomyopathy	Uncertain significance (Aug 01, 2017)
10-86668695-T-A		Myofibrillar myopathy 4	Uncertain significance (Feb 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LDB3	protein_coding	protein_coding	ENST00000429277	13	67620

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000957	0.999	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.287	431	448	0.962	0.0000283	4727
Missense in Polyphen		186	218.21	0.85238		2399
Synonymous	-0.709	200	188	1.07	0.0000132	1509
Loss of Function	2.99	14	32.4	0.432	0.00000176	350

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000416	0.000415
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.000187	0.000185
European (Non-Finnish)	0.000179	0.000176
Middle Eastern	0.0000547	0.0000544
South Asian	0.000231	0.000229
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton. {ECO:0000305}.
• Disease: DISEASE: Left ventricular non-compaction 3 (LVNC3) [MIM:601493]: A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC3 is an autosomal dominant condition. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, myofibrillar, 4 (MFM4) [MIM:609452]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM4 is characterized by distal and proximal muscle weakness with signs of cardiomyopathy and neuropathy. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.324

Intolerance Scores

• loftool: 0.0734
• rvis_EVS: -0.9
• rvis_percentile_EVS: 10.16

Haploinsufficiency Scores

• pHI: 0.867
• hipred: Y
• hipred_score: 0.595
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.978

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ldb3
• Phenotype: digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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); muscle phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: ldb3a
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: structure, cavities

Gene ontology

• Biological process: sarcomere organization
• Cellular component: cytoskeleton;Z disc;pseudopodium;perinuclear region of cytoplasm
• Molecular function: protein kinase C binding;protein binding;cytoskeletal protein binding;metal ion binding;muscle alpha-actinin binding