RAB22A

protein-coding

RAB22A, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases

Gene summary

The protein encoded by this gene is a member of the RAB family of small GTPases. The GTP-bound form of the encoded protein has been shown to interact with early-endosomal antigen 1, and may be involved in the trafficking of and interaction between endosomal compartments. [provided by RefSeq, Jul 2008]

MANE transcript

NM_020673.3

Inheritance

—

ClinVar variants

U:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr20:58,309,715-58,367,507

External References & Databases

Ensembl (ENSG00000124209)

Transcript & Mutation Effects

hg38 • Region Span ~57.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAB22A variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 18

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020673.3. 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			1 clinvar			1
missense			18 clinvar			18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	19	0	0	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020673.3	RefSeq	NP_065724.1	7	MANE Select
ENST00000244040.4	Ensembl	ENSP00000244040.3	7	MANE Select
ENST00000870894.1	Ensembl	ENSP00000540953.1	6	Standard
ENST00000870894.2	Ensembl	ENSP00000540953.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Post-translational protein modification
Metabolism of proteins
RAB geranylgeranylation

Biological Process

intracellular protein transport
endocytosis
endosome organization
Rab protein signal transduction
regulation of vesicle size

Molecular Function

GTPase activity
protein binding
GTP binding
GDP binding

Cellular Component

ruffle
early endosome
late endosome
plasma membrane
endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000244040
Coding exons: 7
Length: 57812
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125717
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.69	62	112	0.552	0.00000641	1271
Missense (PolyPhen)		15	37.418	0.40088		439
Synonymous	-0.00728	42	41.9	1.00	0.00000269	365
Loss of Function	2.38	4	13.4	0.298	8.63e-7	134

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in endocytosis and intracellular protein transport. Mediates trafficking of TF from early endosomes to recycling endosomes (PubMed:16537905). Required for NGF-mediated endocytosis of NTRK1, and subsequent neurite outgrowth (PubMed:21849477). Binds GTP and GDP and has low GTPase activity. Alternates between a GTP-bound active form and a GDP-bound inactive form (PubMed:16537905). {ECO:0000269|PubMed:16537905, ECO:0000269|PubMed:21849477}.;

Recessive Scores

pRec: 0.123

Intolerance Scores

LoFtool: 0.453
RVIS EVS: -0.21
RVIS percentile EVS: 38.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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