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Limb disorders

Gene: IQCE

Amber List (moderate evidence)

IQCE (IQ motif containing E)
EnsemblGeneIds (GRCh38): ENSG00000106012
EnsemblGeneIds (GRCh37): ENSG00000106012
OMIM: 617631, Gene2Phenotype
IQCE is in 2 panels

4 reviews

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Four families reported with bi-allelic variants in this gene. The c.895_904del (p.Val301Serfs*8) was found in three of the families without sharing a common haplotype, suggesting a recurrent mechanism. RNA expression analysis on patients’ fibroblasts showed that the dysfunction of IQCE leads to the dysregulation of genes associated with the hedgehog‐signaling pathway, and zebrafish experiments demonstrated a full spectrum of phenotypes linked to defective cilia: Body curvature, kidney cysts, left–right asymmetry, misdirected cilia in the pronephric duct, and retinal defects. Suggest adding to ciliopathy panel(s).
Created: 1 May 2020, 10:16 a.m. | Last Modified: 1 May 2020, 10:16 a.m.
Panel Version: 2.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Postaxial polydactyly

Publications

Variants in this GENE are reported as part of current diagnostic practice

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting from red to amber, but with recommendation of promoting to green following GMS review. 4 cases now reported.
Created: 18 Jan 2021, 3:55 p.m. | Last Modified: 18 Jan 2021, 3:55 p.m.
Panel Version: 2.22
PMID: 28488682 Umair et al 2017 report a large consanguineous family of Pakistani origin segregating post-axial polydactyly type A in the feet. A homozygous splice acceptor site variant (c.395-1G>A) was identified by WES in the IQCE gene, which completely co-segregated with the phenotype in the family. They report that the Iqce knockout mouse (MGI:1921489) shows various types of skeletal deformities including pre-axial polydactyly, digit abnormalities, and short and long tibia.

PMID: 31549751 - Estrada-Cuzcano et al 2019 - report 3 families with biallelic pathogenic variations in IQCE identified by WES. The same variant c.895_904del (p.Val301Serfs*8) was found in all families without sharing a common haplotype, suggesting a recurrent mechanism. In one family this variant as compound heterozygous with another IQCE variant p.Glu451Argfs*15. These families with post-axial polydactyly were initially recruited as syndromic ciliopathies and two have additional pathogenic variations in other genes (TULP1 and ATP6V1B1) explaining their apparent syndromic phenotype. Functional studies based on the patient's cells or zebrafish (Danio rerio) assays confirm the ciliary role of IQCE.
Created: 18 Jan 2021, 3:54 p.m. | Last Modified: 18 Jan 2021, 3:54 p.m.
Panel Version: 2.21
Genomics England clinical team notes - Agree with red rating. Single paper found splice site variant segregating with postaxial polydactyly in a single family
Created: 9 Sep 2018, 6:19 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polydactyly, postaxial, type A7 OMIM:617642; polydactyly, postaxial, type a7 MONDO:0060550

Publications

Rachel Jones (GSTT)

Red List (low evidence)

PMID: 20610440 Single publication of homozygous splice-site mutation in large consanguineous family identified by whole exome analysis. Segregating with condition in that family.

Knockout mouse has limb phenotype (information from publication above) including polydactyly, digital anomalies and short/long lower limb

No further publications found
Created: 24 Apr 2018, 11:32 a.m.

Phenotypes
617642 POLYDACTYLY, POSTAXIAL, TYPE A7; PAPA7

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: No other evidence found.
Created: 9 Apr 2018, 2:16 p.m.
Comment on publications: PMID: 28488682 one family report.
Created: 9 Apr 2018, 1:09 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Other
Phenotypes
  • Polydactyly, postaxial, type A7 OMIM:617642
  • polydactyly, postaxial, type a7 MONDO:0060550
Tags
for-review
OMIM
617631
Clinvar variants
Variants in IQCE
Penetrance
None
Publications
Panels with this gene

History Filter Activity

18 Jan 2021, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: IQCE.

18 Jan 2021, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: IQCE were changed from Polydactyly, postaxial, type A7 617642 to Polydactyly, postaxial, type A7 OMIM:617642; polydactyly, postaxial, type a7 MONDO:0060550

18 Jan 2021, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: IQCE were set to 28488682

18 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

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

11 Dec 2018, Gel status: 1

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

Ellen McDonagh: Comment on publications: PMID:

9 Apr 2018, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

9 Apr 2018, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

9 Apr 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for IQCE were set to 28488682

9 Apr 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

IQCE was added to Limb disorders panel. Sources: Other

9 Apr 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

IQCE was created by Ellen McDonagh