NEXN

Chr 1ADAR

nexilin F-actin binding protein

Also known as: CDM2M, CMH20, NELIN

NCBI Gene: 91624 ENSG00000162614 UniProt: Q0ZGT2 OMIM: 613121

This gene encodes a filamentous actin-binding protein essential for maintaining Z line and sarcomere integrity in cardiac muscle and regulating cell migration through cytoskeletal interactions. Mutations cause dilated cardiomyopathy (both autosomal dominant and recessive forms) and hypertrophic cardiomyopathy. The gene shows both autosomal dominant and autosomal recessive inheritance patterns depending on the specific cardiomyopathy subtype.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a filamentous actin-binding protein that may function in cell adhesion and migration. Mutations in this gene have been associated with dilated cardiomyopathy, also known as CMD1CC. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1CCMIM #613122

Cardiomyopathy, dilated, 2M, autosomal recessiveMIM #621261

Cardiomyopathy, hypertrophic, 20MIM #613876

UniProtCardiomyopathy, familial hypertrophic, 20

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — NEXN

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.72

OE 0.55 (0.40–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.21Z-score

OE missense 1.03 (0.94–1.13)

354 obs / 343.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.55 (0.40–0.78)

0≤0.351.4

Missense OE?1.03 (0.94–1.13)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 24 / 43.3Missense obs/exp: 354 / 343.1Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in NEXN?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 73

831 rare PASS variants

Rare truncating (LoF)

1 in 930

168 rare PASS variants

Rare synonymous (reference)

1 in 210

268 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NEXN. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 82	1 in 940
South Asian	~43k	1 in 95	1 in 570
Remaining (unassigned)	~30k	1 in 68	1 in 330
European (Finnish)	~27k	1 in 370	1 in 2,700
Admixed American	~22k	1 in 73	1 in 720
African / African American	~21k	1 in 64	1 in 950
East Asian	~20k	1 in 99	1 in 1,000
Ashkenazi Jewish	~13k	1 in 260	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 96	≈ 1 in 940

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 12 coding exons well covered in gnomAD exomes; exons 2, 6 marginal. Genomes: all 12.? see exons ↓