RALGAPA1

Ral GTPase activating protein catalytic subunit alpha 1

Basic information

Region (hg38): 14:35538352-35809304

Previous symbols: [ "GARNL1" ]

Links

ENSG00000174373 ∙ NCBI:253959 ∙ OMIM:608884 ∙ HGNC:17770 ∙ Uniprot:Q6GYQ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AD
• neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation	AR	Pulmonary	Among other findings, individuals have been described with neonatal respiratory insufficiency requiring intervention, and awareness may allow such interventions to be performed efficiently	Craniofacial; Musculoskeletal; Neurologic; Pulmonary	32004447

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RALGAPA1 gene.

• Inborn_genetic_diseases (169 variants)
• not_provided (55 variants)
• Neurodevelopmental_disorder_with_hypotonia,_neonatal_respiratory_insufficiency,_and_thermodysregulation (22 variants)
• RALGAPA1-related_disorder (11 variants)
• Long_QT_syndrome (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RALGAPA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001346249.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				21		21
missense	1		197	12	1	211
nonsense	4	1				5
start loss						0
frameshift	2	2	1			5
splice donor/acceptor (+/-2bp)		1				1
Total	7	4	198	33	1

Highest pathogenic variant AF is 0.000003246163

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RALGAPA1	protein_coding	protein_coding	ENST00000307138	40	270953

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000527	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.53	716	1.04e+3	0.692	0.0000518	13697
Missense in Polyphen		327	551.23	0.59322		7324
Synonymous	0.767	330	348	0.948	0.0000174	3922
Loss of Function	8.03	16	105	0.153	0.00000583	1297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000209	0.000207
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.00	0.00
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.0000818	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000673	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}.
• Pathway: Integrated Breast Cancer Pathway (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.0300
• rvis_EVS: -1.21
• rvis_percentile_EVS: 5.71

Haploinsufficiency Scores

• pHI: 0.752
• hipred: Y
• hipred_score: 0.563
• ghis: 0.652

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ralgapa1

Zebrafish Information Network

• Gene name: ralgapa1
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: regulation of small GTPase mediated signal transduction;activation of GTPase activity
• Cellular component: nucleus;cytoplasm
• Molecular function: GTPase activator activity;protein heterodimerization activity