NEXN

nexilin F-actin binding protein, the group of I-set domain containing

Basic information

Region (hg38): 1:77888513-77943895

Links

ENSG00000162614 ∙ NCBI:91624 ∙ OMIM:613121 ∙ HGNC:29557 ∙ Uniprot:Q0ZGT2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 20 (Limited), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1CC (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 20 (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy (Limited), mode of inheritance: AD
• dilated cardiomyopathy (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic, 20; Cardiomyopathy, dilated, 1CC	AD	Cardiovascular	Surveillance (eg, including echocardiogram/electocardiogram) and preventive measures, including medical management, may reduce morbidity and severe sequelae such as sudden cardiac death; Cardiac transplantation has ben reported	Cardiovascular	19881492; 20970104

ClinVar

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

• Cardiovascular_phenotype (454 variants)
• Dilated_cardiomyopathy_1CC (417 variants)
• Hypertrophic_cardiomyopathy_20 (411 variants)
• not_provided (199 variants)
• not_specified (110 variants)
• Cardiomyopathy (89 variants)
• NEXN-related_disorder (25 variants)
• Primary_dilated_cardiomyopathy (11 variants)
• Hypertrophic_cardiomyopathy (6 variants)
• Primary_familial_hypertrophic_cardiomyopathy (6 variants)
• Dilated_cardiomyopathy_1A (3 variants)
• Hypertrophic_cardiomyopathy_1 (3 variants)
• CARDIOMYOPATHY,_DILATED,_2M (2 variants)
• Left_ventricular_noncompaction_cardiomyopathy (2 variants)
• Long_QT_syndrome (2 variants)
• Primary_familial_dilated_cardiomyopathy (2 variants)
• Hypertrophic_cardiomyopathy_2 (2 variants)
• Premature_ventricular_contraction (1 variants)
• Dilated_Cardiomyopathy,_Dominant (1 variants)
• Heart_failure (1 variants)
• Left_ventricular_hypertrophy (1 variants)
• See_cases (1 variants)
• Arrhythmogenic_right_ventricular_dysplasia_9 (1 variants)
• Dilated_cardiomyopathy_1S (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NEXN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000144573.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	149	2	158
missense	1	1	389	23	2	416
nonsense	5	10	14			29
start loss			1			1
frameshift	10	10	33			53
splice donor/acceptor (+/-2bp)		7	8			15
Total	16	28	452	172	4

Highest pathogenic variant AF is 0.000041552346

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NEXN	protein_coding	protein_coding	ENST00000334785	12	55383

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.91e-11	0.996	124707	1	83	124791	0.000337

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.208	354	343	1.03	0.0000175	4480
Missense in Polyphen		115	104.97	1.0955		1304
Synonymous	0.167	109	111	0.980	0.00000554	1132
Loss of Function	2.72	24	43.3	0.554	0.00000257	521

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000441	0.000439
Ashkenazi Jewish	0.0000994	0.0000993
East Asian	0.000390	0.000389
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000463	0.000459
Middle Eastern	0.000390	0.000389
South Asian	0.000360	0.000327
Other	0.000331	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in regulating cell migration through association with the actin cytoskeleton. Has an essential role in the maintenance of Z line and sarcomere integrity. {ECO:0000269|PubMed:12053183, ECO:0000269|PubMed:15823560, ECO:0000269|PubMed:19881492}.
• Disease: DISEASE: Cardiomyopathy, familial hypertrophic 20 (CMH20) [MIM:613876]: 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:20970104}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.929
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.34

Haploinsufficiency Scores

• pHI: 0.192
• hipred: N
• hipred_score: 0.448
• ghis: 0.539

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0145

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nexn
• 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); 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

Zebrafish Information Network

• Gene name: nexn
• Affected structure: atrium
• Phenotype tag: abnormal
• Phenotype quality: increased width

Gene ontology

• Biological process: homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;response to bacterium;regulation of cell migration;regulation of cytoskeleton organization;dendrite self-avoidance
• Cellular component: cytoskeleton;plasma membrane;focal adhesion;Z disc;axon
• Molecular function: structural constituent of muscle;actin filament binding;cell-cell adhesion mediator activity