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Intellectual disability

Gene: ACAN

Red List (low evidence)

ACAN (aggrecan)
EnsemblGeneIds (GRCh38): ENSG00000157766
EnsemblGeneIds (GRCh37): ENSG00000157766
OMIM: 155760, Gene2Phenotype
ACAN is in 9 panels

4 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Downgraded from Amber to Red in context of the review by Konstantinos Varvagiannis
Created: 9 Oct 2020, 4 p.m. | Last Modified: 9 Oct 2020, 4 p.m.
Panel Version: 3.419

Konstantinos Varvagiannis (Other)

Red List (low evidence)

The different ACAN-related phenotypes or aggrecanopathies are all reviewed by Gibson and Briggs (PMID: 27353333).

Intellectual disability is not among the features of these disorders.

More than 150 affected individuals with ACAN mutations have been reported to date but this was never commented on.

Sentchordi-Montané et al. (PMID: 29464738) describe 16 individuals and review the previously published patients (overview in table 5).

Gkourogianni et al. (PMID: 27870580 - also reviewed in the aforementioned article) in an original report of 103 individuals do not comment on this feature. The questionnaire used for their study (available in the supplement) did not however address the cognitive abilities.

Gibson and Briggs discuss also on the recessive aggrecanopathies:
- A single family with Recessive spondyloepimetaphyseal dysplasia, aggrecan type (OMIM 612813) had been reported at the time. The original report on this family does not mention DD/ID in any family member (PMID: 19110214).
- Concerning Macrocephaly with multiple epiphyseal dysplasia and distinctive facies (OMIM 607131 - commonly referred to as Al-Gazali-Bakalinova syndrome), mild DD/ID was noted in some members of the original family reported by Al-Gazali (PMID: 9689990). In this family homozygosity for ACAN mutations was excluded as a cause in a subsequent study (PMID: 11389160). The disorder has been explained by homozygosity for a KIF7 variant (PMIM: 22587682 - KIF7 is the gene for this entry in OMIM) and does not belong to the aggrecanopathies.

ACAN is included in the DD panel of G2P associated with Spondyloepiphyseal dysplasia type Kimberley and/or Spondyloepimetaphyseal dysplasia aggrecan type.

This gene is not included in ID panels offered by diagnostic laboratories.

As a result, ACAN should probably be demoted to red.
Created: 16 Dec 2018, 7:54 p.m.


BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Loss of function; All missense/in frame
Created: 27 Jul 2017, 4:58 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal


Louise Daugherty (Genomics England Curator)

Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to access inclusion and pertinence to this panel.
Created: 28 Jul 2017, 9:14 a.m.


Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
  • Expert Review Red
  • Spondyloepiphyseal dysplasia, Kimberley type, 608361
  • Spondyloepimetaphyseal dysplasia, aggrecan type, 612813
  • Osteochondritis dissecans, short stature, and early-onset osteoarthritis, 165800
Clinvar variants
Variants in ACAN
Panels with this gene

History Filter Activity

9 Oct 2020, Gel status: 1

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: acan has been classified as Red List (Low Evidence).

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

28 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

27 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

ACAN was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene

27 Jul 2017, Gel status: 0


BRIDGE consortium (NIHRBR-RD)

ACAN was created by BRIDGE