RALA

RAS like proto-oncogene A, the group of RAS type GTPase family

Basic information

Region (hg38): 7:39623565-39708120

Previous symbols: [ "RAL" ]

Links

ENSG00000006451 ∙ NCBI:5898 ∙ OMIM:179550 ∙ HGNC:9839 ∙ Uniprot:P11233 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Strong), mode of inheritance: AD
• Hiatt-Neu-Cooper neurodevelopmental syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hiatt-Neu-Cooper neurodevelopmental syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	30500825; 30761613

ClinVar

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

• Neurodevelopmental delay (1 variants)
• Hiatt-Neu-Cooper neurodevelopmental syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RALA 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				22	1	23
missense	2	7	21	1	5	36
nonsense		1	2			3
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			3	4	2	9
non coding				8	3	11
Total	2	8	25	31	9

Variants in RALA

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

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

Position	Type	Phenotype	Significance	ClinVar
7-39686671-G-A			Benign (Jan 22, 2024)
7-39686699-C-G			Uncertain significance (Jan 11, 2024)
7-39686705-C-T			Uncertain significance (Oct 03, 2023)
7-39686713-A-G		Hiatt-Neu-Cooper neurodevelopmental syndrome	Likely pathogenic (Apr 24, 2023)
7-39686718-C-A			Likely benign (Jan 25, 2024)
7-39686727-G-A			Likely benign (Aug 09, 2022)
7-39686735-G-C		Hiatt-Neu-Cooper neurodevelopmental syndrome	Likely pathogenic (Feb 21, 2023)
7-39686737-G-A			Uncertain significance (Nov 18, 2023)
7-39686739-C-T			Likely benign (Oct 28, 2022)
7-39686740-G-A		Inborn genetic diseases • Hiatt-Neu-Cooper neurodevelopmental syndrome • Intellectual disability	Pathogenic/Likely pathogenic (Apr 17, 2024)
7-39686740-G-T		Hiatt-Neu-Cooper neurodevelopmental syndrome	Pathogenic (Feb 23, 2023)
7-39686776-G-A			Uncertain significance (Nov 15, 2022)
7-39686778-T-C			Likely benign (Jun 07, 2023)
7-39686784-A-G			Uncertain significance (Jan 17, 2022)
7-39686790-T-C			Likely benign (Jun 27, 2022)
7-39686791-A-G			Likely benign (Feb 18, 2022)
7-39686791-A-T			Benign (Jan 14, 2024)
7-39690363-G-A			Likely benign (Jan 10, 2023)
7-39690390-G-A			Likely benign (Oct 14, 2022)
7-39690405-C-G			Likely benign (Jul 31, 2021)
7-39690411-A-T			Likely benign (Jul 23, 2022)
7-39690414-C-T			Likely benign (Sep 01, 2022)
7-39690450-A-G			Likely benign (Jun 16, 2023)
7-39690453-C-A			Likely benign (Dec 25, 2023)
7-39690492-C-T			Likely benign (Jun 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RALA	protein_coding	protein_coding	ENST00000005257	4	84642

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.973	0.0271	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.70	29	108	0.268	0.00000535	1362
Missense in Polyphen		5	53.335	0.093747		650
Synonymous	1.00	32	40.1	0.799	0.00000223	370
Loss of Function	3.09	0	11.1	0.00	7.16e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling (PubMed:20005108). Key regulator of LPAR1 signaling and competes with GRK2 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage- independent proliferation of transformed cells (PubMed:19306925). During mitosis, supports the stabilization and elongation of the intracellular bridge between dividing cells. Cooperates with EXOC2 to recruit other components of the exocyst to the early midbody (PubMed:18756269). {ECO:0000269|PubMed:18756269, ECO:0000269|PubMed:19306925, ECO:0000269|PubMed:20005108}.
• Pathway: Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);RalA downstream regulated genes;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;Chromosomal and microsatellite instability in colorectal cancer;Ras Signaling;EGF-EGFR Signaling Pathway;Signal Transduction;Vesicle-mediated transport;ras signaling pathway;Membrane Trafficking;p38MAPK events;Signalling to RAS;Signalling to ERKs;Signaling by NTRK1 (TRKA);Signaling by NTRKs;ErbB1 downstream signaling;Arf6 trafficking events;Translocation of GLUT4 to the plasma membrane;Signaling by Receptor Tyrosine Kinases;Regulation of p38-alpha and p38-beta;FoxO family signaling (Consensus)

Recessive Scores

• pRec: 0.315

Intolerance Scores

• rvis_EVS: 0.32
• rvis_percentile_EVS: 72.94

Haploinsufficiency Scores

• pHI: 0.352
• hipred: Y
• hipred_score: 0.783
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.958

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rala
• Phenotype: skeleton phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; embryo phenotype; cellular phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: neural tube closure;exocytosis;chemotaxis;cell cycle;signal transduction;Ras protein signal transduction;regulation of exocytosis;actin cytoskeleton reorganization;interleukin-12-mediated signaling pathway;cell division;positive regulation of filopodium assembly;membrane raft localization;membrane organization
• Cellular component: plasma membrane;focal adhesion;cell surface;endocytic vesicle;cytoplasmic vesicle membrane;cleavage furrow;myelin sheath;extracellular exosome;Flemming body
• Molecular function: GTPase activity;protein binding;GTP binding;myosin binding;GDP binding;ubiquitin protein ligase binding;Edg-2 lysophosphatidic acid receptor binding;ATPase binding