RIC1

protein-coding

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

Gene summary

Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in several processes, including positive regulation of GTPase activity; regulation of extracellular matrix constituent secretion; and retrograde transport, endosome to Golgi. Located in cytosol and membrane. Part of Ric1-Rgp1 guanyl-nucleotide exchange factor complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA1432

MANE transcript

NM_020829.4

Inheritance

AR, AD

ClinVar variants

P:2U:198B:41

Top phenotype

Cleft lip, cataract, tooth abnormality, intellectual disability, facial dysmorphism, and attention-deficit hyperactivity disorder (CATIFA syndrome)

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr9:5,629,025-5,776,557

External References & Databases

Ensembl (ENSG00000107036)

Transcript & Mutation Effects

hg38 • Region Span ~147.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Catifa syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032901

Submitter: PanelApp Australia

Catifa syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032901

Submitter: Ambry Genetics

cleft lip/palateSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0016044

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cleft lip, cataract, tooth abnormality, intellectual disability, facial dysmorphism, and attention-deficit hyperactivity disorder (CATIFA syndrome)AR

Manifestation: Craniofacial; Dental; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 27878435; 31932796

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RIC1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 207

not providedTotal: 27

Catifa syndromeTotal: 9

RIC1-related disorderTotal: 8

SeizureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020829.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	23 clinvar	3 clinvar	29
missense		2 clinvar	189 clinvar	14 clinvar	1 clinvar	206
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	2	198	37	4	241

Highest pathogenic variant AF is 0.000003420258

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020829.4	RefSeq	NP_065880.2	26	MANE Select
ENST00000414202.7	Ensembl	ENSP00000416696.2	26	MANE Select
NM_001135920.4	RefSeq	NP_001129392.2	22	Standard
NM_001206557.2	RefSeq	NP_001193486.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Rab regulation of trafficking
Intra-Golgi traffic
RAB GEFs exchange GTP for GDP on RABs

Biological Process

intracellular protein transport
retrograde transport, endosome to Golgi
positive regulation of GTPase activity
negative regulation of cellular protein catabolic process

Molecular Function

protein binding
Rab guanyl-nucleotide exchange factor activity
Rab GTPase binding

Cellular Component

Golgi membrane
cytosol
membrane
integral component of membrane
trans-Golgi network membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000414202
Coding exons: 26
Length: 147533
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0733	747	753	0.992	0.0000382	9330
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.00024	0.00020	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

RVIS EVS: -1.7
RVIS percentile EVS: 2.58

Essentials

Essential (gene trap): N