RAB32

protein-coding

RAB32, member RAS oncogene family, the group of RAB, member RAS oncogene GTPases|A-kinase anchoring proteins

Gene summary

The protein encoded by this gene anchors the type II regulatory subunit of protein kinase A to the mitochondrion and aids in mitochondrial fission. The encoded protein also appears to be involved in autophagy and melanosome secretion. Variations in this gene may be linked to leprosy. [provided by RefSeq, Dec 2015]

MANE transcript

NM_006834.5

Inheritance

ClinVar variants

U:27B:1

Top phenotype

Parkinson disease 26, autosomal dominant, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr6:146,543,833-146,554,953

External References & Databases

Ensembl (ENSG00000118508)

Transcript & Mutation Effects

hg38 • Region Span ~11.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Parkinson disease 26, autosomal dominant, susceptibility toMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0975748

Submitter: PanelApp Australia

Parkinson disease 26, autosomal dominant, susceptibility toMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0975748

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Parkinson disease 26, autosomal dominant, susceptibility toAD

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Levodopa can be beneficial in individuals with Parkinson disease

Refs: 38614108; 38858457

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RAB32 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 2

Parkinson disease 26, autosomal dominant, susceptibility toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006834.5. 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			26 clinvar			26
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	27	1	0	28

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006834.5	RefSeq	NP_006825.1	3	MANE Select
ENST00000367495.4	Ensembl	ENSP00000356465.3	3	MANE Select
ENST00000885997.1	Ensembl	ENSP00000556056.1	3	Standard
ENST00000976884.1	Ensembl	ENSP00000646701.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification
Metabolism of proteins
Rab regulation of trafficking

Biological Process

intracellular protein transport
mitochondrion organization
vesicle-mediated transport
antigen processing and presentation
Rab protein signal transduction

Molecular Function

GTPase activity
protein binding
GTP binding
GTP-dependent protein binding
AP-2 adaptor complex binding

Cellular Component

mitochondrion
mitochondrial outer membrane
early endosome
endoplasmic reticulum
trans-Golgi network

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367495
Coding exons: 3
Length: 11273
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.256	132	124	1.06	0.00000578	1485
Missense (PolyPhen)		35	37.023	0.94535		437
Synonymous	-0.600	56	50.6	1.11	0.00000241	435
Loss of Function	0.964	6	9.15	0.656	5.60e-7	86

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission (PubMed:12186851). Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis (PubMed:21255211). Plays an important role in the control of melanin production and melanosome biogenesis (PubMed:23084991). In concert with RAB38, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (By similarity). {ECO:0000250|UniProtKB:Q9CZE3, ECO:0000269|PubMed:12186851, ECO:0000269|PubMed:21255211, ECO:0000269|PubMed:23084991}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.555
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.557

Gene Damage Prediction

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