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

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.

• Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (6 variants)
• Infantile spasms;Generalized hypotonia;Respiratory distress;Feeding difficulties (5 variants)
• Inborn genetic diseases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				16		16
missense	1		101	6	2	110
nonsense	4					4
start loss						0
frameshift	2	2	1			5
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			3	1		4
non coding				1	3	4
Total	7	3	102	23	5

Variants in RALGAPA1

This is a list of pathogenic ClinVar variants found in the RALGAPA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-35539615-A-G		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
14-35539644-C-A		Inborn genetic diseases	Uncertain significance (Aug 12, 2021)
14-35539687-G-A		Inborn genetic diseases	Uncertain significance (Aug 30, 2021)
14-35549194-G-T		Inborn genetic diseases	Uncertain significance (Jun 16, 2023)
14-35549217-C-G		Long QT syndrome	Likely benign (-)
14-35570654-G-A			Uncertain significance (Aug 05, 2024)
14-35570675-C-T		Inborn genetic diseases	Uncertain significance (Dec 07, 2022)
14-35570703-A-T		Inborn genetic diseases	Uncertain significance (Jan 18, 2023)
14-35570727-G-C			Likely benign (Oct 01, 2024)
14-35570736-G-C		Inborn genetic diseases	Uncertain significance (Sep 20, 2023)
14-35570749-T-C		Inborn genetic diseases	Uncertain significance (Dec 29, 2023)
14-35572561-T-C		Inborn genetic diseases	Uncertain significance (May 15, 2023)
14-35572564-G-T		Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation	Uncertain significance (Jan 19, 2024)
14-35572678-G-C		Infantile spasms;Generalized hypotonia;Respiratory distress;Feeding difficulties • Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation	Pathogenic (Sep 24, 2019)
14-35595667-C-T		Inborn genetic diseases	Uncertain significance (May 27, 2022)
14-35595687-A-ATATT		Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation	Likely pathogenic (-)
14-35595726-T-C		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
14-35595775-G-T		Inborn genetic diseases	Uncertain significance (May 08, 2023)
14-35605634-T-C			Benign/Likely benign (Nov 01, 2024)
14-35605694-C-T			Likely benign (Jul 01, 2022)
14-35627049-G-GA		Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation	Benign (Nov 07, 2021)
14-35627109-T-A		Inborn genetic diseases	Uncertain significance (Jan 31, 2024)
14-35627113-C-A		Inborn genetic diseases	Uncertain significance (Feb 09, 2023)
14-35627117-A-G		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
14-35627148-C-G		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)

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