Congenital myopathy

Gene: PACSIN3

Amber List (moderate evidence)

PACSIN3 (protein kinase C and casein kinase substrate in neurons 3)
EnsemblGeneIds (GRCh38): ENSG00000165912
EnsemblGeneIds (GRCh37): ENSG00000165912
OMIM: 606513, Gene2Phenotype
PACSIN3 is in 3 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are two unrelated families and functional evidence including mouse model in support of the disease association. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 9 Jun 2026, 7:18 p.m. | Last Modified: 9 Jun 2026, 7:18 p.m.
Panel Version: 7.49
PMID:38637313 (2024) reported three individuals from two unrelated families presenting with childhood-onset myopathy with hyperCKaemia. They were identified with either compound heterozygous or homozygous loss-of-function variants in PACSIN3 gene via exome sequencing and confirmed by Sanger sequencing (Family 1: c.270_277del, p.Leu91AlafsTer15 and c.609_610del, p(Lys203AsnfsTer4; Family 2: c.592G>T, p.Glu198Ter), which segregated with the disorder in the two families. Ultrastructural studies in muscle tissue derived from Individual 1 showed accumulation of membranous tubules, some of which were arranged in tubular aggregates.

PMID:29202928 (2017) reported evidence from Syndapin III knockout mice, which are viable, fertile, and developed without obvious impairments under normal conditions. But, their muscle cells showed a severe reduction in caveolar invaginations without loss of caveolin3 or cavin1 from the plasma membrane . Upon physical exercise, the knockout skeletal muscles exhibited pathological features including widened fibre calibre, detached nuclei, inflammation, and necrosis - phenocopying human myopathies associated with CAV3 mutations.

This gene has been associated with relevant phenotypes in both OMIM (MIM # 621343, last accessed 09 June 2026) and Gene2Phenotype (with 'moderate' rating on the DD panel).
Created: 9 Jun 2026, 7:14 p.m. | Last Modified: 9 Jun 2026, 7:16 p.m.
Panel Version: 7.46

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital myopathy 27, OMIM:621343; congenital myopathy 27, MONDO:0979897

Publications

Anna Sarkozy (Great Ormond Street Hospital)

Green List (high evidence)

variants cause childhood-onset myopathy with hyperCKaemia
Created: 27 May 2026, 9:42 a.m. | Last Modified: 27 May 2026, 9:42 a.m.
Panel Version: 7.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Congenital myopathy 27, OMIM:621343
  • congenital myopathy 27, MONDO:0979897
Tags
Q2_26_promote_green Q2_26_NHS_review
OMIM
606513
Clinvar variants
Variants in PACSIN3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Jun 2026, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: pacsin3 has been classified as Amber List (Moderate Evidence).

9 Jun 2026, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: PACSIN3 were changed from to Congenital myopathy 27, OMIM:621343; congenital myopathy 27, MONDO:0979897

9 Jun 2026, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: PACSIN3 were set to

9 Jun 2026, Gel status: 0

Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_26_promote_green tag was added to gene: PACSIN3. Tag Q2_26_NHS_review tag was added to gene: PACSIN3.

27 May 2026, Gel status: 0

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: pacsin3 has been removed from the panel.

27 May 2026, Gel status: 1

Created, Added New Source, Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

gene: PACSIN3 was added gene: PACSIN3 was added to Congenital myopathy. Sources: NHS GMS Mode of inheritance for gene: PACSIN3 was set to BIALLELIC, autosomal or pseudoautosomal