RALGAPBRal GTPase activating protein non-catalytic beta subunit
Autism Reports / Total Reports
4 / 5Rare Variants / Common Variants
11 / 0Aliases
RALGAPB, KIAA1219, RalGAPbetaAssociated Syndromes
-Chromosome Band
20q11.23Associated Disorders
-Relevance to Autism
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013).
Molecular Function
Non-catalytic subunit of the heterodimeric RalGAP1 and RalGAP2 complexes which act as GTPase activators for the Ras-like small GTPases RALA and RALB.
Reports related to RALGAPB (5 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | De novo mutations in epileptic encephalopathies | Epi4K Consortium , et al. (2013) | No | - |
2 | Primary | Synaptic, transcriptional and chromatin genes disrupted in autism | De Rubeis S , et al. (2014) | Yes | - |
3 | Recent Recommendation | Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model | Guo H , et al. (2018) | Yes | - |
4 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
5 | Support | Excess of RALGAPB de novo variants in neurodevelopmental disorders | Shah AA et al. (2020) | Yes | - |
Rare Variants (11)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.974A>G | p.Tyr325Cys | missense_variant | De novo | NA | Simplex | 30564305 | Guo H , et al. (2018) | |
c.3423G>A | p.Thr1141= | synonymous_variant | De novo | NA | - | 25363760 | De Rubeis S , et al. (2014) | |
c.1928dup | p.Asn643LysfsTer3 | frameshift_variant | De novo | NA | - | 30564305 | Guo H , et al. (2018) | |
c.1238C>T | p.Thr413Met | missense_variant | De novo | NA | Simplex | 32853829 | Shah AA et al. (2020) | |
c.523G>A | p.Asp175Asn | missense_variant | Familial | Maternal | Simplex | 30564305 | Guo H , et al. (2018) | |
c.1573dup | p.Cys525LeufsTer2 | frameshift_variant | De novo | NA | - | 31452935 | Feliciano P et al. (2019) | |
c.1010G>A | p.Arg337His | missense_variant | Familial | Paternal | Simplex | 30564305 | Guo H , et al. (2018) | |
c.2731G>A | p.Gly911Ser | missense_variant | Familial | Paternal | Simplex | 30564305 | Guo H , et al. (2018) | |
c.3860C>G | p.Ser1287Ter | stop_gained | De novo | NA | Simplex | 23934111 | Epi4K Consortium , et al. (2013) | |
c.865_866del | p.Met289ValfsTer3 | frameshift_variant | De novo | NA | - | 25363760 | De Rubeis S , et al. (2014) | |
c.4376G>A | p.Arg1459Gln | missense_variant | Unknown | Not paternal | Simplex | 30564305 | Guo H , et al. (2018) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
Score Delta: Decreased from 2 to 1
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
10/1/2021

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
7/1/2021

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
4/1/2021

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
1/1/2021

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
10/1/2020

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
7/1/2020

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
4/1/2020

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
1/1/2020

Decreased from 2 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
10/1/2019

Decreased from 3 to 1
New Scoring Scheme
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013). An additional de novo likely gene-disruptive variant in the RALGAPB gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019.
7/1/2019

Decreased from 3 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013).
4/1/2019

Decreased from 3 to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013).
1/1/2019

Increased from to 1
Description
Two de novo frameshift variants and one de novo missense variant in the RALGAPB gene were identified in ASD probands in De Rubeis et al., 2014 and Guo et al., 2018. A de novo nonsense variant in this gene had previously been identified in a patient with epileptic encephalopathy (Epi4K Consortium 2013).
Krishnan Probability Score
Score 0.33679581133934
Ranking 24333/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99999995563256
Ranking 168/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.56017799159087
Ranking 591/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score 0.37467875662867
Ranking 1733/20870 scored genes
[Show Scoring Methodology]