Bleeding and platelet disorders

Gene: RAP1B

Green List (high evidence)

Comment on list classification: As reviewed by Carl Fratter, gain-of-function missense variants in RAP1B are known to cause thrombocytopenia. At least 3 unrelated cases of RAP1B-associated syndromic thrombocytopenia have been reported in literature (PMID: 32627184 Niemann et al., 2020; PMID: 35451551 Miller et al., 2022). Hence, this gene should be upgraded to Green on Bleeding and platelet disorders.

RAP1B is associated with Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, MIM:620654 in OMIM (accessed 29th Dec 2025).

Created: 29 Dec 2025, 4:09 p.m. | Last Modified: 29 Dec 2025, 4:09 p.m.

Panel Version: 4.2

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, OMIM:620654

Publications

• 32627184
• 35451551

Green List (high evidence)

Specific gain-of-function missense variants have been associated with this disorder to date.
RAP1B is already included as a green gene on other panels, including the R91 cytopenia panel.
It would be appropriate to add this gene to the R90 panel, as other syndromic thrombocytopenia associated genes are included on this panel. This opinion is supported by the Central&South GLH haemostasis genomics MDT.
Sources: Expert Review

Created: 12 Dec 2025, 5:29 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies (OMIM #620654)

Publications

• PMID: 32627184
• 35451551
• 37850357

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments