Familial Hirschsprung Disease

Gene: SEMA3C

Amber List (moderate evidence)

SEMA3C (semaphorin 3C)
EnsemblGeneIds (GRCh38): ENSG00000075223
EnsemblGeneIds (GRCh37): ENSG00000075223
OMIM: 602645, Gene2Phenotype
SEMA3C is in 1 panel

3 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Amber (and added 'watchlist' tag) to match Erwin's review and after discussion with Helen Brittain. On original expert list as cluster of genes (SEMA 3A/C/D), and insufficient cases to currently support causation.
Created: 28 Aug 2017, 9:28 a.m.
In a GWAS study PMID:25839327 (Jiang et al., 2015) studied 220 child-parent trios of European ancestry with S-HSCR and identified 9 SNPs at 7 loci, including the semaphorin gene cluster. To assess the role of class 3 semaphorins in HSCR beyond the genetic association, they sequenced SEMA3A,C and D genes in 254 HSCR cases and identified 12 non-synonymous variants. Among these, 3 variants in SEMA3C and 3 variants in SEMA3D were selected as being likely causal based largely on model systems.
Created: 14 Aug 2017, 3:27 p.m.

Erwin Brosens (Erasmus MC)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sumita Chhabra (University of Liverpool / Alder Hey Children's Hospital)

animal model confirmation. functional test confirming deleterious variants
Created: 8 May 2017, 10:36 a.m.


Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Expert Review Amber
  • Alder Hey - Erasmus MC
  • susceptibility to Hirschsprung disease
Clinvar variants
Variants in SEMA3C
Panels with this gene

History Filter Activity

18 Oct 2017, Gel status: 2

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

18th October 2017: Revised and approved to Version 1.0 after expert and curator review. An expert list from Mr. Simon Kenny and Professor Robert Hofstra's groups (Alder Hey - Erasmus MC) formed the basis of the original panel. The expert list was then expanded based on a review of literature. Many of the literature genes remain red on the V1.0 panel as they were identified through association studies and/or they represent susceptibility/risk factors for Hirschsprung's disease (HSCR). Sumita Chhabra (Alder Hey) and Erwin Brosens (Erasmus) provided extensive feedback for genes on the panel, together with reviews from Merce Garcia-Barcelo.

28 Aug 2017, Gel status: 2

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Amber List (Moderate Evidence).

28 Aug 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for SEMA3C was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

14 Aug 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for SEMA3C were set to 25839327

8 May 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

SEMA3C was added to Familial Hirschprungs Diseasepanel. Sources: Alder Hey - Erasmus MC

8 May 2017, Gel status: 0


Rebecca Foulger (Genomics England curator)

SEMA3C was created by rfoulger