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Fetal anomalies

Gene: NEXN

Green List (high evidence)
NEXN (nexilin F-actin binding protein)
EnsemblGeneIds (GRCh38): ENSG00000162614
EnsemblGeneIds (GRCh37): ENSG00000162614
OMIM: 613121, Gene2Phenotype
NEXN is in 7 panels

5 reviews

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

Green List (high evidence)

This gene and phenotype were reviewed during meetings in June & July 2025. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Elizabeth Scotchman (North Thames GLH), Natalie Bibb, Stephanie Allen & Sarah Graham (Central & South GLH) and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Elizabeth Wall, Sunayna Best, Soo-Mi Park & Sahar Mansour (R21 Clinical Oversight Group).
Created: 5 Sep 2025, 4:31 p.m. | Last Modified: 5 Sep 2025, 4:31 p.m.
Panel Version: 6.28
Currently Amber. New report of two male infants with prenatal diagnosis of dilated cardiomyopathy with impaired ventricular contractility, one with hydrops and polyhydramnios - one patient with homozygous c.1156dup (p.Met386fs) and one with homozygous c.1579_1584del p.(Glu527_Glu528del) (39183344). Previous literature: homozygous c.1302del p.(Ile435Serfs*3) in three fetuses of the same couple with IUD due to dilated cardiomyopathy (35166435).; homozygous c.1174C > T,p.(R392*) in 1 fetus with hydrops (33949776); compound het c.1756A>T;p.(Lys586*) and c.1909_1912del;p.(Tyr637Alafs*684) in one fetus (32058062). Biallelic variants in 5 unrelated families, sufficient for green rating. Heterozygous variants associated with milder DCM phenotype; heterozygous parents may be mildly affected.
Created: 5 Sep 2025, 2:55 p.m. | Last Modified: 5 Sep 2025, 2:55 p.m.
Panel Version: 6.24

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cardiomyopathy

Publications

Created: 5 Sep 2025, 2:55 p.m.
Last Modified: 5 Sep 2025, 2:55 p.m.
Panel version: 6.28

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 12 Dec 2025, 3:10 p.m. | Last Modified: 12 Dec 2025, 3:10 p.m.
Panel Version: 6.120
This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.
Panel Version: 4.36
Created: 29 Aug 2024, 8:33 p.m.
Last Modified: 29 Aug 2024, 8:33 p.m.
Panel version: 6.120

Lyn Chitty (Great Ormond Street NHS Foundation Trust)

I don't know

Usually late onset, one paed resolved, two swedish families lethal cardiomyopathy. Keep amber. Need more cases
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.
Panel Version: 4.35

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Lethal fetal cardiomyopathy; Cardiomyopathy, dilated 1CC, OMIM:613122; Hydrops fetalis

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

There is sufficient evidence to promote this gene to Green at the next GMS panel update, inline with the recent review by the R21 Clinical Oversight Group. MOI has also been updated from 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' to 'BIALLELIC, autosomal or pseudoautosomal' as per the review.
Created: 5 Sep 2025, 4:41 p.m. | Last Modified: 16 Dec 2025, 12:13 p.m.
Panel Version: 6.121
Comment on list classification: New gene added to this panel by Rhiannon Mellis (GOSH). Rating Amber in view of two unrelated cases presenting with a fetal phenotype reported to date (added watchlist tag).
Created: 9 Aug 2022, 1:18 p.m. | Last Modified: 9 Aug 2022, 1:18 p.m.
Panel Version: 1.887
Created: 9 Aug 2022, 1:18 p.m.
Last Modified: 16 Dec 2025, 12:13 p.m.
Panel version: 6.29

Rhiannon Mellis (Great Ormond Street Hospital)

I don't know

This gene and phenotype were reviewed during a meeting on 21st July 2022 between representatives of the North Thames and Central & South R21 testing GLHs.
Clinical review and curation was performed by Lyn Chitty, Alison Male, Rhiannon Mellis (North Thames GLH), and Stephanie Allen, Denise Williams, Esther Kinning and Anna de Burca (Central & South GLH).

Outcome of review: Gene usually causes adult-onset AD cardiomyopathy. However, there may be a fetally relevant phenotype with biallelic variants. Support adding to the Fetal anomalies panel as an Amber gene, pending more evidence of fetal phenotype (only 2 reported unrelated cases to date).

Currently rated Green on the following other PanelApp panel(s): Cardiomyopathy (dilated)

Details of review: The fetal case in Sparks et al (PMID: 33027564) had pericardial effusion, ascites, cardiomegaly, dilation and hypertrophy of cardiac ventricles, hypoplastic and dysplastic aortic valve, diminished systolic function, fetal growth restriction, and was stillborn. 2 NEXN variants found in the fetus (1 mat inherited, 1 de novo) but unable to confirm phase.
The fetal case in Rinaldi et al 2021 (PMID: 32058062) had Cardiomegaly, low contractility/outflow, fibroelastosis of right ventricle. The fetus was compound het for NEXN variants and parents were both unaffected het with normal echos. They'd had one previous pregnancy with same phenotype.
Sources: Literature, Expert Review
Created: 1 Aug 2022, 5:17 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cardiomyopathy

Publications

Created: 1 Aug 2022, 5:17 p.m.

Panel version: 1.880

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Cardiomyopathy
  • Cardiomyopathy, dilated, 1CC, OMIM:613122
  • Cardiomyopathy, hypertrophic, 20, OMIM:613876
OMIM
613121
Clinvar variants
Variants in NEXN
Penetrance
None
Publications
Panels with this gene

History Filter Activity

16 Dec 2025, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_25_promote_green was removed from gene: NEXN. Tag Q3_25_NHS_review was removed from gene: NEXN.

12 Dec 2025, Gel status: 3

Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Green was added to NEXN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

8 Sep 2025, Gel status: 2

Removed Tag, Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: NEXN. Tag Q3_25_promote_green tag was added to gene: NEXN. Tag Q3_25_NHS_review tag was added to gene: NEXN.

5 Sep 2025, Gel status: 2

Set mode of inheritance, Set Phenotypes, Set publications

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene NEXN was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Cardiomyopathy for gene: NEXN Publications for gene: NEXN were updated from 33947203; 32058062; 35166435; 33027564; 33949776 to 39183344; 33947203; 33949776; 33027564; 35166435; 32058062

29 Aug 2024, Gel status: 2

Added New Source, Set mode of inheritance, Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to NEXN. Mode of inheritance for gene NEXN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: NEXN were updated from 32058062; 33027564 to 33947203; 32058062; 35166435; 33027564; 33949776

9 Aug 2022, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: NEXN were changed from Cardiomyopathy to Cardiomyopathy, dilated, 1CC, OMIM:613122; Cardiomyopathy, hypertrophic, 20, OMIM:613876

9 Aug 2022, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: NEXN were set to PMID: 32058062; PMID: 33027564

9 Aug 2022, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: nexn has been classified as Amber List (Moderate Evidence).

9 Aug 2022, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: NEXN.

1 Aug 2022, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Rhiannon Mellis (Great Ormond Street Hospital)

gene: NEXN was added gene: NEXN was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: NEXN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEXN were set to PMID: 32058062; PMID: 33027564 Phenotypes for gene: NEXN were set to Cardiomyopathy Review for gene: NEXN was set to AMBER