Intellectual disability
Gene: RAP1B

RAP1B (RAP1B, member of RAS oncogene family)
EnsemblGeneIds (GRCh38): ENSG00000127314
EnsemblGeneIds (GRCh37): ENSG00000127314
OMIM: 179530, Gene2Phenotype
RAP1B is in 9 panels

4 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 3 May 2024, 11:55 a.m. | Last Modified: 3 May 2024, 11:55 a.m.

Panel Version: 6.11

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 3 May 2024, 11:55 a.m.
Last Modified: 3 May 2024, 11:55 a.m.
Panel version: 6.11

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.
Created: 6 Nov 2023, 4:51 p.m. | Last Modified: 6 Nov 2023, 4:51 p.m.

Panel Version: 5.334

PMID:35451551 - New patient reported with mild intellectual disability, bicuspid aortic valve, dilation of aortic root and ascending aorta, hearing loss, and long‐standing thrombocytopenia with lymphopenia. A novel, missense RAP1B variant (p.Ala59Gly) has been identified in this patient. This variant is on the neighbouring amino acid to one of the previously reported variants (p.Gly60Arg). This variant is confirmed de novo and not in gnomAD.

This gene has been associated with relevant phenotype in Gene2Phenotype database (with 'limited' rating in the DD panel), but not yet been associated with phenotypes in OMIM.
Created: 6 Nov 2023, 4:48 p.m. | Last Modified: 6 Nov 2023, 4:48 p.m.

Panel Version: 5.332

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

35451551

Created: 6 Nov 2023, 4:48 p.m.
Last Modified: 6 Nov 2023, 4:48 p.m.
Panel version: 5.332

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in Gene2Phenotype but not OMIM.

PMID: 32627184 describes 2 patients.
36 yo patient of non-consanguineous parents. Had unclear pancytopenia, multiple congenital malformations, mild intellectual disability, endocrine disorders (short stature with growth hormone deficiency), dysmorphism and other features. Parents and sibling unaffected.
13 yo of non-consanguineous parents with thrombocytopenia, multiple congenital anomalies and learning difficulties. He had normal developmental milestones, walk was achieved at 14 months and there was no speech delay. He attended mainstream school with auxiliary help because of learning difficulties with graphism, syntaxic comprehension, logical reasoning and attention deficit. Parents and siblings unaffected.

PMID: 26280580 describes another patient with variant in RAP1B. The clinical features can be found in supplementary table 2. The table lists ID, but doesn't say severity and lists a host of other features including short stature, facial dysmorphism and skeletal findings.

All 3 cases seem to have a very wide spectrum of differing phenotypes and therefore, this gene has been given an Amber rating until further evidence is available.
Created: 21 Dec 2020, 10:48 a.m. | Last Modified: 21 Dec 2020, 10:48 a.m.

Panel Version: 3.661

Created: 21 Dec 2020, 10:48 a.m.
Last Modified: 21 Dec 2020, 10:48 a.m.
Panel version: 3.661

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Three unrelated individuals reported with de novo variants, some functional data. One of them described as Kabuki-like but lacks typical facial gestalt.
Sources: Literature
Created: 9 Dec 2020, 8:37 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Syndromic intellectual disability

Publications

Created: 9 Dec 2020, 8:37 a.m.

Panel version: 3.644

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

NHS GMS
Expert Review Green

Phenotypes

Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, OMIM:620654
Syndromic intellectual disability

OMIM

179530

Clinvar variants

Variants in RAP1B

Penetrance

None

Publications

Panels with this gene

History Filter Activity

27 Oct 2025, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: RAP1B were changed from Syndromic intellectual disability to Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, OMIM:620654; Syndromic intellectual disability

3 May 2024, Gel status: 3