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Intellectual disability

Gene: TRPS1

Amber List (moderate evidence)

TRPS1 (transcriptional repressor GATA binding 1)
EnsemblGeneIds (GRCh38): ENSG00000104447
EnsemblGeneIds (GRCh37): ENSG00000104447
OMIM: 604386, Gene2Phenotype
TRPS1 is in 7 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark
Created: 17 Aug 2020, 10:18 a.m. | Last Modified: 17 Aug 2020, 10:18 a.m.
Panel Version: 3.254

Zornitza Stark (Australian Genomics)

Red List (low evidence)

ID is not typically part of the phenotype.
Created: 2 Mar 2020, 2:52 a.m. | Last Modified: 2 Mar 2020, 2:52 a.m.
Panel Version: 3.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Trichorhinophalangeal syndrome, type I (MIM 190350); Trichorhinophalangeal syndrome, type III (MIM 190351)

Konstantinos Varvagiannis (Other)

I don't know

Mutations in TRPS1 cause Trichorhinophalangeal syndrome, type I (MIM 190350) or Trichorhinophalangeal syndrome, type III (MIM 190351). According to OMIM these individuals have normal intelligence (clinical synopses).

Trichorhinophalangeal syndrome type II (MIM 150230 or Langer-Giedion syndrome) is caused by 8q24.1 deletions spanning TRPS1, EXT1 and RAD21 (gene associated with Cornelia de Lange syndrome 4 - MIM 614701). Intellectual disability is a feature of this type.

In a review on Trichorhinophalangeal syndrome, Maas et al. (PMID: 28426188) comment specifically that "The proportion of individuals with TRPS I with intellectual disability is similar to that in the general population; in contrast, two thirds of individuals with TRPS II have mild-to-moderate intellectual disability. Delay in motor development is usually associated with hip dysplasia and, therefore, likely to be secondary". In this context, they cite a previous report of 103 cytogenetically and molecularly confirmed individuals with TRPS (same authors among many others - PMID: 25792522).

There are however few reports on individuals with TRPS1 variants and intellectual disability, notably the following (most proposed in the first article below):
- Gilman et al. (PMID: 28256045) - 1 individual with a frameshift variant
- Lüdecke et al. (PMID: 11112658) - at least 4 individuals with certain ID and missense/nonsense mutations (and some further with possible ID)
- Gonzalez-Huerta et al. (PMID: 17689056) - 1 individual with 2-basepair deletion.
- Sidler et al. (PMID: 22127049) - Mother and 2 affected children, the 2 latter presenting with confirmed ID (mother at the lower end of the normal range, although not formally evaluated). All were heterozygous for NM_014112.2:c.2894G>A or p.Arg965His (previously referred to as p.Arg952His using NM_014112.1 as a reference). The authors underline the fact that ID was not a feature in other patients with mutations of the same codon as in PMIDs: 14560312 (Kaiser et al. - Arg952Cys and Arg952His) or 17854380 (Rossi et al. - Arg952Cys).

TRPS1 is included in the DD panel in G2P.

The gene is included in gene panels for ID offered by some diagnostic laboratories.

As a result, this gene should possibly remain amber.
Created: 15 Dec 2018, 9:25 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Trichorhinophalangeal syndrome, type I (MIM 190350); Trichorhinophalangeal syndrome, type III (MIM 190351)


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

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
Created: 27 Jul 2017, 8:47 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown


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, 4:52 p.m.


Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Expert Review Amber
  • Trichorhinophalangeal syndrome, type I, 190350
  • Trichorhinophalangeal syndrome, type III, 190351
Clinvar variants
Variants in TRPS1
Panels with this gene

History Filter Activity

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)

TRPS1 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene

27 Jul 2017, Gel status: 0


BRIDGE consortium (NIHRBR-RD)

TRPS1 was created by BRIDGE