RAP1GDS1

protein-coding

Rap1 GTPase-GDP dissociation stimulator 1, the group of Armadillo repeat containing

Gene summary

The smg GDP dissociation stimulator (smgGDS) protein is a stimulatory GDP/GTP exchange protein with GTPase activity (Riess et al., 1993 [PubMed 8262526]).[supplied by OMIM, Feb 2010]

MANE transcript

NM_001100427.2

Inheritance

ClinVar variants

P:3U:76B:6

Top phenotype

Alfadhel syndrome

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr4:98,261,384-98,443,858

External References & Databases

Ensembl (ENSG00000138698)

Transcript & Mutation Effects

hg38 • Region Span ~182.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Alfadhel syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0958001

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Alfadhel syndromeAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

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: 32431071; 33875846

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAP1GDS1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 9

Alfadhel syndromeTotal: 4

RAP1GDS1-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001100427.2. 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	2 clinvar	5
missense		1 clinvar	71 clinvar	1 clinvar		73
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)	1 clinvar		3 clinvar			4
Total	2	1	76	4	2	85

Highest pathogenic variant AF is 0.000025080006

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 128 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001100427.2	RefSeq	NP_001093897.1	15	MANE Select
ENST00000408927.8	Ensembl	ENSP00000386153.4	15	MANE Select
NM_001100426.2	RefSeq	NP_001093896.1	15	Standard
NM_001100428.2	RefSeq	NP_001093898.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of RAC1 activity

Biological Process

vascular smooth muscle contraction
myosin filament assembly
negative regulation of endoplasmic reticulum calcium ion concentration
positive regulation of GTPase activity
positive regulation of mitochondrial calcium ion concentration

Molecular Function

GTPase activator activity
protein binding

Cellular Component

mitochondrion
endoplasmic reticulum
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000339360
Coding exons: 15
Length: 182478
Individuals with no LoFs: 124767
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 124794
p: 0.000108

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	252	305	0.827	0.0000141	3998
Missense (PolyPhen)		58	84.46	0.68671		1156
Synonymous	0.929	95	107	0.886	0.00000506	1161
Loss of Function	4.29	5	30.6	0.163	0.00000157	388

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0	0.0	absent
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stimulates GDP/GTP exchange reaction of a group of small GTP-binding proteins (G proteins) including Rap1a/Rap1b, RhoA, RhoB and KRas, by stimulating the dissociation of GDP from and the subsequent binding of GTP to each small G protein.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.825
RVIS EVS: -0.03
RVIS percentile EVS: 51.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.640

Gene Damage Prediction

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