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Cytopenias and congenital anaemias

Gene: RAP1B

Green List (high evidence)

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

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: There are three unrelated cases with cytopenia and hence this gene has been upgraded from Amber to Green. This gene is already Green on the GMS equivalent panel - https://panelapp.genomicsengland.co.uk/panels/519/gene/RAP1B/

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: 27 Oct 2025, 9:48 a.m. | Last Modified: 27 Oct 2025, 9:48 a.m.
Panel Version: 1.121

Ivone Leong (Genomics England Curator)

I don't know

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. Cytopenia is not a feature for this patient.

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.
Sources: Literature
Created: 21 Dec 2020, 11:17 a.m.

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

Phenotypes
Syndromic intellectual disability; cytopenia

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, OMIM:620654
  • Syndromic intellectual disability
  • Cytopenia
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; cytopenia to Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, OMIM:620654; Syndromic intellectual disability; Cytopenia

27 Oct 2025, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: rap1b has been classified as Green List (High Evidence).

27 Oct 2025, Gel status: 2

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: RAP1B.

21 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: rap1b has been classified as Amber List (Moderate Evidence).

21 Dec 2020, Gel status: 1

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Ivone Leong (Genomics England Curator)

gene: RAP1B was added gene: RAP1B was added to Cytopenias and congenital anaemias. Sources: Literature watchlist tags were added to gene: RAP1B. Mode of inheritance for gene: RAP1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RAP1B were set to 32627184; 26280580 Phenotypes for gene: RAP1B were set to Syndromic intellectual disability; cytopenia Review for gene: RAP1B was set to AMBER