RIC1

RIC1 homolog, RAB6A GEF complex partner 1, the group of WD repeat domain containing

Basic information

Region (hg38): 9:5629025-5776557

Previous symbols: [ "KIAA1432" ]

Links

ENSG00000107036 ∙ NCBI:57589 ∙ OMIM:610354 ∙ HGNC:17686 ∙ Uniprot:Q4ADV7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Catifa syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cleft lip, cataract, tooth abnormality, intellectual disability, facial dysmorphism, and attention-deficit hyperactivity disorder (CATIFA syndrome)	AR	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; Dental; Neurologic; Ophthalmologic	27878435; 31932796

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RIC1 gene.

• not_specified (164 variants)
• not_provided (25 variants)
• Catifa_syndrome (9 variants)
• RIC1-related_disorder (7 variants)
• Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020829.4. 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			1	13	3	17
missense		2	163	12	1	178
nonsense			1			1
start loss						0
frameshift			2			2
splice donor/acceptor (+/-2bp)						0
Total	0	2	167	25	4

Highest pathogenic variant AF is 0.000003420258

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIC1	protein_coding	protein_coding	ENST00000414202	26	147533

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00116	0.999	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0733	747	753	0.992	0.0000382	9330
Missense in Polyphen		127	199.62	0.63621		2434
Synonymous	-5.29	376	266	1.41	0.0000130	2735
Loss of Function	5.85	21	76.1	0.276	0.00000419	840

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000240	0.000239
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.000272	0.000272
Finnish	0.000236	0.000231
European (Non-Finnish)	0.000240	0.000202
Middle Eastern	0.000272	0.000272
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP and may thereby required for efficient fusion of endosome-derived vesicles with the Golgi compartment. The RIC1- RGP1 complex participates in the recycling of mannose-6-phosphate receptors. Required for phosphorylation and localization of GJA1. {ECO:0000269|PubMed:16112082, ECO:0000269|PubMed:23091056}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;Intra-Golgi traffic;RAB GEFs exchange GTP for GDP on RABs;Retrograde transport at the Trans-Golgi-Network;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• rvis_EVS: -1.7
• rvis_percentile_EVS: 2.58

Haploinsufficiency Scores

• pHI: 0.190
• hipred: Y
• hipred_score: 0.544
• ghis: 0.634

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Ric1
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; hematopoietic system phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; immune system phenotype

Gene ontology

• Biological process: intracellular protein transport;retrograde transport, endosome to Golgi;positive regulation of GTPase activity;negative regulation of cellular protein catabolic process
• Cellular component: Golgi membrane;cytosol;membrane;integral component of membrane;trans-Golgi network membrane;protein-containing complex;RIC1-RGP1 guanyl-nucleotide exchange factor complex
• Molecular function: protein binding;Rab guanyl-nucleotide exchange factor activity;Rab GTPase binding