RAB32

Summary

RAB32 (RAB32, member RAS oncogene family, HGNC:9772) is a protein-coding gene on chromosome 6q24.3, encoding Ras-related protein Rab-32 (Q13637). The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

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.

Source: NCBI Gene 10981 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Parkinson disease 26, autosomal dominant, susceptibility to (Moderate, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 28 total
• Phenotypes (HPO): 45
• MANE Select transcript: NM_006834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9772
Approved symbol	RAB32
Name	RAB32, member RAS oncogene family
Location	6q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000118508
Ensembl biotype	protein_coding
OMIM	612906
Entrez	10981

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000367495, ENST00000885997

RefSeq mRNA: 1 — MANE Select: NM_006834 NM_006834

CCDS: CCDS5210

Canonical transcript exons

ENST00000367495 — 3 exons

Exon	Start	End
ENSE00000799046	146549464	146549741
ENSE00001444767	146554456	146554953
ENSE00001444771	146543833	146544121

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 98.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.9050 / max 516.3732, expressed in 1727 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70366	27.9420	1679
70365	7.0778	1506
70363	3.2793	1423
70364	0.9907	690
70362	0.4534	169
70361	0.1619	54

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.08	gold quality
mononuclear cell	CL:0000842	97.80	gold quality
leukocyte	CL:0000738	97.64	gold quality
mucosa of transverse colon	UBERON:0004991	95.95	gold quality
granulocyte	CL:0000094	95.28	gold quality
stromal cell of endometrium	CL:0002255	94.09	gold quality
smooth muscle tissue	UBERON:0001135	94.06	gold quality
ascending aorta	UBERON:0001496	93.62	gold quality
thoracic aorta	UBERON:0001515	93.55	gold quality
spleen	UBERON:0002106	93.29	gold quality
rectum	UBERON:0001052	93.23	gold quality
left coronary artery	UBERON:0001626	93.15	gold quality
blood	UBERON:0000178	93.10	gold quality
aorta	UBERON:0000947	93.04	gold quality
popliteal artery	UBERON:0002250	92.84	gold quality
tibial artery	UBERON:0007610	92.82	gold quality
right coronary artery	UBERON:0001625	92.58	gold quality
transverse colon	UBERON:0001157	92.35	gold quality
descending thoracic aorta	UBERON:0002345	92.21	gold quality
bone marrow	UBERON:0002371	92.16	gold quality
islet of Langerhans	UBERON:0000006	92.07	gold quality
right testis	UBERON:0004534	91.90	gold quality
upper lobe of left lung	UBERON:0008952	91.87	gold quality
coronary artery	UBERON:0001621	91.83	gold quality
left testis	UBERON:0004533	91.67	gold quality
omental fat pad	UBERON:0010414	91.42	gold quality
peritoneum	UBERON:0002358	91.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.06	gold quality
upper lobe of lung	UBERON:0008948	91.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.00	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	258.27
E-MTAB-6701	yes	44.82
E-CURD-112	yes	31.36
E-HCAD-1	yes	24.20
E-HCAD-13	yes	22.62
E-MTAB-8142	yes	20.63
E-MTAB-9067	yes	16.30
E-MTAB-9221	yes	15.56
E-HCAD-9	yes	15.31
E-MTAB-9388	yes	12.91
E-CURD-122	yes	10.54
E-CURD-88	yes	8.13
E-MTAB-10042	yes	7.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting RAB32, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1227-3P	97.36	66.94	834
HSA-MIR-6789-3P	83.91	59.77	58

Literature-anchored findings (GeneRIF, showing 19)

• Rab32 is a dual function protein that participates in both mitochondrial anchoring of PKA and synchronization of mitochondrial fission. (PMID:12186851)
• RAB32 inactivation may represent a component of the oncogenic pathway of microsatellite-unstable gastrointestinal adenocarcinomas (PMID:16557577)
• Results suggest that Rab32 facilitates the formation of autophagic vacuoles whose membranes are derived from the ER and regulates the clearance of aggregated proteins by autophagy. (PMID:19593531)
• Identification of two new loci at IL23R and RAB32 that influence susceptibility to leprosy (PMID:22019778)
• that Rab38 and Rab32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs. (PMID:22511774)
• BLOC-3 is a Rab32 and Rab38 guanine nucleotide exchange factor, with a specific function in the biogenesis of lysosome-related organelles. (PMID:23084991)
• Rab38 and its close homolog Rab32 bind to Myosin Vc but not to Myosin Va or Myosin Vb. Binding depends on residues in the switch II region of Rab32 and Rab38 and regions of the Myosin Vc coiled-coil tail domain. (PMID:25324551)
• Rab32 may regulate the physiological functions of LRRK2. (PMID:25360523)
• Rab32 controls intracellular lipid accumulation through inducing lipolysis via enhancing ATGL expression indirectly. (PMID:26882978)
• this study provides some compelling evidence showing that Rab32 is an essential host factor required for HCV particle assembly and thus that Rab32 could be a potential therapeutic target to interrupt HCV propagation. (PMID:27852857)
• Expression of a T39N mutant Rab32 protein arrests mitochondria movement within neurites of differentiated SH-SY5Y cells. (PMID:29261068)
• megalin is critical for mitochondrial biology; mitochondrial intracrine signaling is a continuum of the retrograde early endosome-to-Golgi-Rab32 pathway and defects in this pathway may underlie disease processes in many systems. (PMID:29916093)
• The data imply that Rab32 is linked to SNX6/retromer trafficking at the Golgi, and also suggests a possible connection between the retromer and Rab32 in the trafficking and biological functions of LRRK2. (PMID:30640902)
• This study showed that RAB32 and RHOT2 were associated with aging, and that individuals exhibiting methylation levels of the RAB32 CpG site higher than 10% were observed more prone to disability than people with lower levels. (PMID:30787202)
• The small GTPase Rab32 resides on lysosomes to regulate mTORC1 signaling. (PMID:32295849)
• Rab32 promotes glioblastoma migration and invasion via regulation of ERK/Drp1-mediated mitochondrial fission. (PMID:36922509)
• Deciphering the molecular regulatory of RAB32/GPRC5A axis in chronic obstructive pulmonary disease. (PMID:38448858)
• RAB32 Ser71Arg in autosomal dominant Parkinson’s disease: linkage, association, and functional analyses. (PMID:38614108)
• Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson’s disease. (PMID:38858457)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab32a	ENSDARG00000029036
danio_rerio	rab32b	ENSDARG00000041165

Paralogs (68): RAB27B (ENSG00000041353), RAB27A (ENSG00000069974), RAB7A (ENSG00000075785), RABL2B (ENSG00000079974), RAB21 (ENSG00000080371), RAB10 (ENSG00000084733), RAB18 (ENSG00000099246), RAB36 (ENSG00000100228), IFT27 (ENSG00000100360), RAB40AL (ENSG00000102128), RAB11A (ENSG00000103769), RAB2A (ENSG00000104388), RAB3D (ENSG00000105514), RAB3A (ENSG00000105649), RAB5C (ENSG00000108774), RAB34 (ENSG00000109113), RAB5B (ENSG00000111540), RAB35 (ENSG00000111737), RAB23 (ENSG00000112210), DNAJC27 (ENSG00000115137), RAB29 (ENSG00000117280), RAB14 (ENSG00000119396), RAB9B (ENSG00000123570), RAB9A (ENSG00000123595), RAB38 (ENSG00000123892), RAB22A (ENSG00000124209), RAB17 (ENSG00000124839), RAB2B (ENSG00000129472), RAB25 (ENSG00000132698), RAB33A (ENSG00000134594), RAB30 (ENSG00000137502), RAB1A (ENSG00000138069), RAB20 (ENSG00000139832), RAB15 (ENSG00000139998), RAB40B (ENSG00000141542), RAB13 (ENSG00000143545), RABL2A (ENSG00000144134), RAB5A (ENSG00000144566), RAB19 (ENSG00000146955), RAB41 (ENSG00000147127)

Protein

Protein identifiers

Ras-related protein Rab-32 — Q13637 (reviewed: Q13637)

All UniProt accessions (1): Q13637

UniProt curated annotations — full annotation on UniProt →

Function. The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Also 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. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. Plays an important role in the control of melanin production and melanosome biogenesis. In concert with RAB38, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes. Stimulates phosphorylation of RAB10 ‘Thr-73’ by LRRK2.

Subunit / interactions. Interacts with ANKRD27. A decreased interaction with ANKRD27 seen in the presence of SGSM2. Interacts with LRRK2 (via N-terminus); this interaction results in stimulation of RAB10 phosphorylation by LRRK2.

Subcellular location. Mitochondrion. Mitochondrion outer membrane. Cytoplasmic vesicle. Phagosome. Phagosome membrane. Melanosome. Melanosome membrane.

Tissue specificity. Widely expressed with high levels in heart, liver, kidney, bone marrow, testis, colon and fetal lung.

Disease relevance. Parkinson disease 26, autosomal dominant (PARK26) [MIM:620923] An autosomal dominant form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK26 shows incomplete penetrance. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Regulated by guanine the nucleotide exchange factor (GEF) BLOC-3 complex composed of HPS1 and HPS4 which promote the exchange of bound GDP for free GTP. Regulated by the GTPase activating protein (GAP) SGSM2/RUTBC1 which increases the GTP hydrolysis activity. Inhibited by GDP dissociation inhibitors (GDIs) which prevent Rab-GDP dissociation.

Domain organisation. Switch I, switch II and the interswitch regions are characteristic of Rab GTPases and mediate the interactions with Rab downstream effectors. The switch regions undergo conformational changes upon nucleotide binding which drive interaction with specific sets of effector proteins, with most effectors only binding to GTP-bound Rab.

Similarity. Belongs to the small GTPase superfamily. Rab family.

RefSeq proteins (1): NP_006825* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030697	Rab29/Rab38/Rab32	Family

Pfam: PF00071

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (51 total): binding site 18, mutagenesis site 9, strand 7, helix 6, region of interest 3, modified residue 2, lipid moiety-binding region 2, initiator methionine 1, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6FF8	X-RAY DIFFRACTION	2.13
5OEC	X-RAY DIFFRACTION	2.3
4CYM	X-RAY DIFFRACTION	2.8
5OED	X-RAY DIFFRACTION	2.9
4CZ2	X-RAY DIFFRACTION	2.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13637-F1	84.60	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (18): 40; 51; 52; 54; 57; 57; 81; 84; 143; 144; 146; 175 …

Post-translational modifications (4): 2, 71, 224, 225

Mutagenesis-validated functional residues (9):

Position	Phenotype
39	decreased gtp-binding activity.
85	no change in gtpase activity.
89	impairs interaction with ankrd27; when associated with s-90 and l-94.
90	impairs interaction with ankrd27; when associated with t-89 and l-94.
91	impairs interaction with ankrd27; when associated with s-93.
93	impairs interaction with ankrd27; when associated with m-91.
94	impairs interaction with ankrd27; when associated with t-89 and s-90.
185	abolishes binding to protein kinase a type ii regulatory subunit.
188	abolishes binding to protein kinase a type ii regulatory subunit.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8873719	RAB geranylgeranylation
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 325 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, HALMOS_CEBPA_TARGETS_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_CELLULAR_PIGMENTATION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_PIGMENTATION, GOCC_TRANS_GOLGI_NETWORK, FOSTER_TOLERANT_MACROPHAGE_DN, WANG_RESPONSE_TO_BEXAROTENE_DN, GOBP_PHAGOSOME_MATURATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION

GO Biological Process (9): intracellular protein transport (GO:0006886), mitochondrion organization (GO:0007005), vesicle-mediated transport (GO:0016192), antigen processing and presentation (GO:0019882), melanosome organization (GO:0032438), endosome to melanosome transport (GO:0035646), protein localization to membrane (GO:0072657), phagosome maturation (GO:0090382), melanosome assembly (GO:1903232)

GO Molecular Function (10): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), GTP-dependent protein binding (GO:0030742), AP-1 adaptor complex binding (GO:0035650), AP-3 adaptor complex binding (GO:0035651), BLOC-2 complex binding (GO:0036461), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (17): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), trans-Golgi network (GO:0005802), cytosol (GO:0005829), endomembrane system (GO:0012505), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), melanosome membrane (GO:0033162), melanosome (GO:0042470), mitochondria-associated endoplasmic reticulum membrane contact site (GO:0044233), phagocytic vesicle (GO:0045335), Golgi apparatus (GO:0005794), organelle membrane (GO:0031090), cytoplasmic vesicle (GO:0031410), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
protein-containing complex binding	3
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
intracellular protein localization	2
organelle organization	2
endomembrane system	2
membrane-bounded organelle	2
protein transport	1
intracellular transport	1
transport	1
cellular process	1
immune system process	1
pigment granule organization	1
endosome to pigment granule transport	1
localization within membrane	1
phagolysosome assembly	1
exocytosis	1
melanosome organization	1
organelle assembly	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
mitochondrial membrane	1
organelle outer membrane	1
endosome	1
Golgi apparatus subcompartment	1
vacuole	1
plasma membrane	1
endocytic vesicle membrane	1
phagocytic vesicle	1
melanosome	1
chitosome	1

Protein interactions and networks

STRING

1240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB32	ANKRD27	Q96NW4	951
RAB32	PRKACA	P17612	767
RAB32	PRKACB	P22694	767
RAB32	RASA1	P20936	708
RAB32	PRKACG	P22612	679
RAB32	EXOC6	Q8TAG9	653
RAB32	ZFYVE27	Q5T4F4	644
RAB32	PRKAR2A	P13861	640
RAB32	PHB2	Q99623	638
RAB32	AKAP1	Q92667	628
RAB32	HPS4	Q9NQG7	627
RAB32	RABGEF1	Q9UJ41	620
RAB32	SGSM2	O43147	605
RAB32	RAB3IP	Q96QF0	605
RAB32	ANK1	P16157	587

IntAct

75 interactions, top by confidence:

A	B	Type	Score
RAB32	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.750
RAB32	LRRK2	psi-mi:“MI:0915”(physical association)	0.750
LRRK2	RAB32	psi-mi:“MI:0915”(physical association)	0.750
LRRK2	RAB32	psi-mi:“MI:0403”(colocalization)	0.750
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RAB32	RAB38	psi-mi:“MI:0915”(physical association)	0.670
RAB32	CHM	psi-mi:“MI:0914”(association)	0.640
PPP3R2	RAB32	psi-mi:“MI:0915”(physical association)	0.560
RAB32	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
LRMDA	RAB32	psi-mi:“MI:0915”(physical association)	0.560
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
	RAB32	psi-mi:“MI:0570”(protein cleavage)	0.440
RAB32	SMCR8	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
RAB32	Lrrk2	psi-mi:“MI:0915”(physical association)	0.400
RAB32	PHF20L1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): RAB32 (Affinity Capture-RNA), RAB32 (Affinity Capture-RNA), CLTCL1 (Affinity Capture-MS), CHML (Affinity Capture-MS), CHM (Affinity Capture-MS), RAB38 (Affinity Capture-MS), RABGGTA (Affinity Capture-MS), ABCA2 (Affinity Capture-MS), MRE11A (Affinity Capture-MS), FUBP1 (Affinity Capture-MS), INADL (Affinity Capture-MS), TRIM29 (Affinity Capture-MS), PHF20L1 (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), DOCK6 (Affinity Capture-MS)

ESM2 similar proteins: A1DZY4, A6QP66, O35626, O35929, O88910, O88954, P0C0E4, P35295, P51157, P51158, P53667, P53668, P53669, P55040, P55041, P55043, P63032, P63033, Q06AU5, Q12829, Q13368, Q13637, Q3SWY9, Q5E9J3, Q5FVY2, Q5R541, Q5RFI2, Q6DGN0, Q6IMA3, Q6IMA7, Q6IMB1, Q6P0U3, Q6T310, Q8AVS6, Q8IYK8, Q8QFP8, Q8VEL9, Q8VHP8, Q8VHQ4, Q8WXH6

Diamond homologs: A4FV54, F1PTE3, H9BW96, O04157, O14966, O24461, O76742, O94655, O97572, P01123, P09527, P11023, P16976, P17609, P18067, P19892, P20336, P22125, P22127, P24408, P24409, P28188, P31022, P32939, P33723, P34140, P35280, P35283, P35284, P35286, P36864, P40392, P51149, P51150, P51151, P51152, P51153, P55258, P57729, P61006

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
BLOC-3	“up-regulates activity”	RAB32	“guanine nucleotide exchange factor”
RAB32	“up-regulates activity”	BLOC-2	relocalization
RAB32	“up-regulates activity”	“AP-3 complex”	relocalization
RAB32	“up-regulates activity”	“AP-1 complex”	relocalization
RAB32	“up-regulates activity”	“Neuronal AP-3”	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

28 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

267 predictions. Top by Δscore:

Variant	Effect	Δscore
6:146544121:GGTA:G	donor_loss	1.0000
6:146544122:G:T	donor_loss	1.0000
6:146544123:T:G	donor_loss	1.0000
6:146549453:T:G	acceptor_gain	1.0000
6:146549462:A:AG	acceptor_gain	1.0000
6:146549462:AG:A	acceptor_gain	1.0000
6:146549463:G:GT	acceptor_gain	1.0000
6:146549463:GG:G	acceptor_gain	1.0000
6:146549463:GGGC:G	acceptor_gain	1.0000
6:146549463:GGGCA:G	acceptor_gain	1.0000
6:146549737:CAAAG:C	donor_loss	1.0000
6:146549739:AAGGT:A	donor_loss	1.0000
6:146549740:AGGTG:A	donor_loss	1.0000
6:146549742:G:GG	donor_gain	1.0000
6:146549742:GT:G	donor_loss	1.0000
6:146549743:T:A	donor_loss	1.0000
6:146554450:TTACA:T	acceptor_loss	1.0000
6:146554451:TACAG:T	acceptor_loss	1.0000
6:146554453:CA:C	acceptor_loss	1.0000
6:146554454:A:AG	acceptor_gain	1.0000
6:146554454:AGGA:A	acceptor_loss	1.0000
6:146554455:G:GG	acceptor_gain	1.0000
6:146544118:GCGG:G	donor_gain	0.9900
6:146544120:GG:G	donor_gain	0.9900
6:146544121:GG:G	donor_gain	0.9900
6:146544122:G:GG	donor_gain	0.9900
6:146549451:T:G	acceptor_gain	0.9900
6:146549452:A:AG	acceptor_gain	0.9900
6:146549457:T:G	acceptor_gain	0.9900
6:146549462:AGG:A	acceptor_gain	0.9900

AlphaMissense

1495 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:146544055:T:C	F62L	1.000
6:146544057:C:A	F62L	1.000
6:146544057:C:G	F62L	1.000
6:146544109:T:A	W80R	1.000
6:146544109:T:C	W80R	1.000
6:146544113:A:C	D81A	1.000
6:146544113:A:T	D81V	1.000
6:146543981:G:A	G37D	0.999
6:146543983:A:C	K38Q	0.999
6:146543984:A:T	K38M	0.999
6:146543985:G:C	K38N	0.999
6:146543985:G:T	K38N	0.999
6:146543987:C:T	T39I	0.999
6:146544002:G:C	R44P	0.999
6:146544019:T:C	F50L	0.999
6:146544021:C:A	F50L	0.999
6:146544021:C:G	F50L	0.999
6:146544041:C:T	T57I	0.999
6:146544046:G:A	G59R	0.999
6:146544046:G:C	G59R	0.999
6:146544047:G:A	G59E	0.999
6:146544111:G:C	W80C	0.999
6:146544111:G:T	W80C	0.999
6:146544112:G:C	D81H	0.999
6:146544113:A:G	D81G	0.999
6:146544114:C:A	D81E	0.999
6:146544114:C:G	D81E	0.999
6:146549571:T:A	W120R	0.999
6:146549571:T:C	W120R	0.999
6:146549644:A:T	K144I	0.999

dbSNP variants (sampled 300 via entrez): RS1000070338 (6:146542856 T>G), RS1000525078 (6:146543136 A>C), RS1000864870 (6:146548064 G>A,T), RS1000918642 (6:146548304 T>C), RS1001212341 (6:146555104 A>T), RS1001576959 (6:146542486 T>C), RS1001790067 (6:146543606 G>A), RS1001844051 (6:146543450 C>T), RS1002043187 (6:146549650 A>G), RS1002106177 (6:146550857 A>C,G), RS1002269008 (6:146554314 C>A), RS1002274075 (6:146554671 A>G), RS1002423979 (6:146547524 A>G), RS1002480054 (6:146547921 C>A,G), RS1002532025 (6:146554074 T>A)

Disease associations

OMIM: gene MIM:612906 | disease phenotypes: MIM:620923

GenCC curated gene-disease

Disease	Classification	Inheritance
Parkinson disease 26, autosomal dominant, susceptibility to	Moderate	Autosomal dominant

Mondo (1): Parkinson disease 26, autosomal dominant, susceptibility to (MONDO:0975748)

Orphanet (0):

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000012	Urinary urgency
HP:0000716	Depression
HP:0000726	Dementia
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000822	Hypertension
HP:0001254	Lethargy
HP:0001271	Polyneuropathy
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002172	Postural instability
HP:0002185	Neurofibrillary tangles
HP:0002304	Akinesia
HP:0002312	Clumsiness
HP:0002322	Resting tremor
HP:0002378	Hand tremor
HP:0002527	Falls
HP:0002548	Parkinsonism with favorable response to dopaminergic medication
HP:0002592	Gastric ulcer
HP:0002615	Hypotension
HP:0002664	Neoplasm
HP:0003401	Paresthesia
HP:0003418	Back pain
HP:0003584	Late onset

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001292_1	Leprosy	4.000000e-14
GCST002772_5	Leprosy	1.000000e-22
GCST004009_10	Leprosy	5.000000e-08
GCST009391_1476	Metabolite levels	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010464	beta-aminoisobutyric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — RAB subfamily

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	3
bisphenol S	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
nickel sulfate	decreases expression	2
Cadmium	increases abundance, increases expression	2
Tunicamycin	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	increases expression	1
ochratoxin A	affects binding	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, affects reaction	1
ICG 001	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Fluvastatin	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TI13	HAP1 RAB32 (-) 1	Cancer cell line	Male
CVCL_TI14	HAP1 RAB32 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.