RABEPK

Summary

RABEPK (Rab9 effector protein with kelch motifs, HGNC:16896) is a protein-coding gene on chromosome 9q33.3, encoding Rab9 effector protein with kelch motifs (Q7Z6M1). Rab9 effector required for endosome to trans-Golgi network (TGN) transport.

Predicted to be involved in receptor-mediated endocytosis and vesicle docking involved in exocytosis. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 10244 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_005833

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16896
Approved symbol	RABEPK
Name	Rab9 effector protein with kelch motifs
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	RAB9P40, bA65N13.1
Ensembl gene	ENSG00000136933
Ensembl biotype	protein_coding
OMIM	605962
Entrez	10244

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 40 protein_coding

ENST00000259460, ENST00000373538, ENST00000373544, ENST00000394125, ENST00000416065, ENST00000628863, ENST00000899267, ENST00000899268, ENST00000899269, ENST00000899270, ENST00000899271, ENST00000899272, ENST00000899273, ENST00000899274, ENST00000899275, ENST00000899276, ENST00000899277, ENST00000899278, ENST00000899279, ENST00000899280, ENST00000936394, ENST00000936395, ENST00000936396, ENST00000936397, ENST00000936398, ENST00000936399, ENST00000936400, ENST00000936401, ENST00000936402, ENST00000936403, ENST00000936404, ENST00000936405, ENST00000936406, ENST00000936407, ENST00000936408, ENST00000936409, ENST00000936410, ENST00000971789, ENST00000971790, ENST00000971791

RefSeq mRNA: 3 — MANE Select: NM_005833 NM_001174152, NM_001174153, NM_005833

CCDS: CCDS55341, CCDS6862

Canonical transcript exons

ENST00000373538 — 8 exons

Exon	Start	End
ENSE00000983738	125213370	125213522
ENSE00001091401	125207564	125207721
ENSE00001091402	125203008	125203066
ENSE00001460792	125233688	125234161
ENSE00001460808	125200542	125200906
ENSE00003492430	125232596	125232745
ENSE00003616793	125220539	125220700
ENSE00003649457	125227910	125228059

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 93.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3015 / max 85.5826, expressed in 1808 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98496	14.6699	1804
98498	1.7831	1008
98497	0.8485	574

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	93.51	gold quality
buccal mucosa cell	CL:0002336	92.66	gold quality
nucleus accumbens	UBERON:0001882	91.19	gold quality
putamen	UBERON:0001874	91.12	gold quality
cervix squamous epithelium	UBERON:0006922	90.56	silver quality
liver	UBERON:0002107	90.54	gold quality
caudate nucleus	UBERON:0001873	90.44	gold quality
cortical plate	UBERON:0005343	90.39	gold quality
prefrontal cortex	UBERON:0000451	90.04	gold quality
stromal cell of endometrium	CL:0002255	89.60	gold quality
right frontal lobe	UBERON:0002810	89.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.57	gold quality
cingulate cortex	UBERON:0003027	88.20	gold quality
middle temporal gyrus	UBERON:0002771	88.10	gold quality
anterior cingulate cortex	UBERON:0009835	87.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.94	gold quality
islet of Langerhans	UBERON:0000006	87.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.81	gold quality
frontal cortex	UBERON:0001870	87.78	gold quality
substantia nigra	UBERON:0002038	87.70	gold quality
neocortex	UBERON:0001950	87.68	gold quality
hypothalamus	UBERON:0001898	87.54	gold quality
amygdala	UBERON:0001876	87.42	gold quality
telencephalon	UBERON:0001893	87.38	gold quality
adenohypophysis	UBERON:0002196	87.33	gold quality
forebrain	UBERON:0001890	87.29	gold quality
right coronary artery	UBERON:0001625	87.24	gold quality
midbrain	UBERON:0001891	87.13	gold quality
left coronary artery	UBERON:0001626	87.04	gold quality
ascending aorta	UBERON:0001496	86.99	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting RABEPK, 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-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-6754-3P	98.84	66.60	889

Literature-anchored findings (GeneRIF, showing 1)

• p40 interaction with PIKfyve p40 os demonstrated; PIKfyve interaction and the subsequent PIKfyve-catalyzed p40 phosphorylation anchor p40 to discrete membranes facilitating late endosome-to-TGN transport. (PMID:14530284)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rabepk	ENSDARG00000112165
mus_musculus	Rabepk	ENSMUSG00000070953
rattus_norvegicus	Rabepk	ENSRNOG00000018591

Paralogs (10): FBXO42 (ENSG00000037637), LZTR1 (ENSG00000099949), KLHDC4 (ENSG00000104731), HCFC2 (ENSG00000111727), KLHDC3 (ENSG00000124702), KLHDC10 (ENSG00000128607), KLHDC9 (ENSG00000162755), KLHDC2 (ENSG00000165516), HCFC1 (ENSG00000172534), KLHDC1 (ENSG00000197776)

Protein

Protein identifiers

Rab9 effector protein with kelch motifs — Q7Z6M1 (reviewed: Q7Z6M1)

Alternative names: 40 kDa Rab9 effector protein, p40

All UniProt accessions (6): A0A024R8A0, A0A0S2Z4Z1, A0A0S2Z4Z5, Q7Z6M1, Q5T1S4, Q5T1S5

UniProt curated annotations — full annotation on UniProt →

Function. Rab9 effector required for endosome to trans-Golgi network (TGN) transport.

Subunit / interactions. Interacts with PIKFYVE; the interaction recruits RABEPK to the endosomal membrane. Interacts with RAB9 in its GTP-bound conformation.

Subcellular location. Cytoplasm. Endosome membrane.

Post-translational modifications. Phosphorylated on Ser residues by PIKFYVE.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z6M1-1	1	yes
Q7Z6M1-2	2

RefSeq proteins (3): NP_001167623, NP_001167624, NP_005824* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR052124	Rab9_kelch_effector	Family

Pfam: PF24681

UniProt features (19 total): sequence variant 7, repeat 5, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6M1-F1	89.40	0.83

Functional residue map

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

Post-translational modifications (1): 133

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6811440	Retrograde transport at the Trans-Golgi-Network

MSigDB gene sets: 162 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, HEIDENBLAD_AMPLICON_8Q24_DN, GGGTGGRR_PAX4_03, GOBP_MEMBRANE_DOCKING, WEI_MYCN_TARGETS_WITH_E_BOX, SCHUHMACHER_MYC_TARGETS_UP, GOBP_EXOCYTOSIS, GOCC_TRANS_GOLGI_NETWORK, GOBP_VESICLE_DOCKING_INVOLVED_IN_EXOCYTOSIS, GOBP_SECRETION, GARY_CD5_TARGETS_DN, GOBP_IMPORT_INTO_CELL, GOBP_VESICLE_DOCKING

GO Biological Process (2): receptor-mediated endocytosis (GO:0006898), obsolete vesicle docking involved in exocytosis (GO:0006904)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): endosome (GO:0005768), cytosol (GO:0005829), endosome membrane (GO:0010008), transport vesicle (GO:0030133), trans-Golgi network membrane (GO:0032588), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Intra-Golgi and retrograde Golgi-to-ER traffic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endomembrane system	2
cytoplasmic vesicle	2
endocytosis	1
binding	1
cytoplasm	1
endosome	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
trans-Golgi network	1
organelle membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RABEPK	ZNF557	Q8N988	536
RABEPK	ZNF358	Q9NW07	510
RABEPK	XPNPEP1	Q9NQW7	481
RABEPK	LRFN5	Q96NI6	459
RABEPK	TTC8	Q8TAM2	453
RABEPK	DOC2A	Q14183	449
RABEPK	LRRC8E	Q6NSJ5	446
RABEPK	MYRIP	Q8NFW9	445
RABEPK	IQCB1	Q15051	437
RABEPK	ALDH6A1	Q02252	428
RABEPK	STX8	Q9UNK0	426
RABEPK	MRC2	Q9UBG0	422
RABEPK	CKAP5	Q14008	418
RABEPK	VAMP1	P23763	414
RABEPK	Q3KRG4	Q3KRG4	413

IntAct

26 interactions, top by confidence:

A	B	Type	Score
TSC22D4	TSC22D2	psi-mi:“MI:0914”(association)	0.640
CFAP20	SFSWAP	psi-mi:“MI:0914”(association)	0.620
SPINDOC	SPIN3	psi-mi:“MI:0914”(association)	0.560
CACNG5	ZNF316	psi-mi:“MI:0914”(association)	0.530
MISP	OBSL1	psi-mi:“MI:0914”(association)	0.530
CCR6	PODXL	psi-mi:“MI:0914”(association)	0.530
RABEPK	GLUL	psi-mi:“MI:0915”(physical association)	0.370
RABEPK	POR	psi-mi:“MI:0915”(physical association)	0.370
RABEPK	PRKRA	psi-mi:“MI:0915”(physical association)	0.370
TMEM98	RABEPK	psi-mi:“MI:0915”(physical association)	0.370
ZYX	RABEPK	psi-mi:“MI:0915”(physical association)	0.370
K5	ATP6AP2	psi-mi:“MI:0914”(association)	0.350
TESK1	ACACB	psi-mi:“MI:0914”(association)	0.350
TMEM169	GPR89A	psi-mi:“MI:0914”(association)	0.350
RABEPK	ST3GAL3	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
RIPPLY1	PGAM2	psi-mi:“MI:0914”(association)	0.350
CFAP20	RABEPK	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
RABEPK	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
TMEM169	PTGES3L-AARSD1	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): RABEPK (Affinity Capture-MS), RABEPK (Co-fractionation), RABEPK (Two-hybrid), RABEPK (Affinity Capture-MS), RABEPK (Affinity Capture-MS), RABEPK (Affinity Capture-MS), RABEPK (Affinity Capture-MS), RABEPK (Reconstituted Complex), RABEPK (Affinity Capture-Western), RABEPK (Biochemical Activity), RABEPK (Reconstituted Complex), RABEPK (Two-hybrid), RABEPK (Affinity Capture-MS), RABEPK (Two-hybrid), TESK1 (Affinity Capture-MS)

ESM2 similar proteins: A2AAX3, A2AGL3, B0LPN4, D3ZA50, D4ABP9, E9Q401, G3X9X1, P30957, Q0IIC2, Q15413, Q28DE7, Q3KRE6, Q3UGM2, Q4G5Y1, Q4R3J7, Q58CV6, Q5E9A7, Q5F361, Q5M9G8, Q5R7H5, Q5RDA9, Q5RDY3, Q5U3Y0, Q5U580, Q5ZJU2, Q6AYI2, Q6P3S6, Q6PAR0, Q6PDJ6, Q6PID8, Q6ZN16, Q7Z6M1, Q80YG3, Q8BGZ3, Q8BM85, Q8IY47, Q8N7A1, Q8TEA7, Q8TEB1, Q8VDD9

Diamond homologs: A1XLE2, G1FNI6, O04316, O04318, O49326, Q4V8F4, Q5EA50, Q5ZJ37, Q6GQN7, Q7Z6M1, Q80YG3, Q8N7A1, Q8RY71, Q93XW5, Q9SDM9, O14248, P38853, P50090, P80197, P87061, Q39610, Q5Z8K3, Q67UX0, Q6AXB2, Q86L99, Q8VCH5, Q8W420, Q8W4K1, Q94BT6, D3ZN95, P51610, P51611, Q54C94, Q5E9A7, Q5RKG2, Q61191, Q6AYI2, Q8RWD9, Q8VEM9, Q9D968

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RAB9A	“up-regulates activity”	RABEPK
RABEPK	“up-regulates activity”	IGF2R	relocalization
RABEPK	“up-regulates activity”	M6PR	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1610 predictions. Top by Δscore:

Variant	Effect	Δscore
9:125203056:A:T	donor_gain	1.0000
9:125203067:GTCT:G	donor_gain	1.0000
9:125203071:G:GG	donor_gain	1.0000
9:125203076:G:GT	donor_gain	1.0000
9:125203077:A:T	donor_gain	1.0000
9:125203099:A:AG	donor_gain	1.0000
9:125227905:TCTA:T	acceptor_loss	1.0000
9:125227906:CTA:C	acceptor_loss	1.0000
9:125227908:A:AG	acceptor_gain	1.0000
9:125227908:AGA:A	acceptor_loss	1.0000
9:125227909:G:GA	acceptor_loss	1.0000
9:125227909:G:GG	acceptor_gain	1.0000
9:125227909:GAC:G	acceptor_gain	1.0000
9:125227909:GACA:G	acceptor_gain	1.0000
9:125228053:GATA:G	donor_gain	1.0000
9:125228055:TATAA:T	donor_gain	1.0000
9:125228056:A:AG	donor_gain	1.0000
9:125228056:A:G	donor_gain	1.0000
9:125228056:ATAA:A	donor_loss	1.0000
9:125228057:TAAG:T	donor_loss	1.0000
9:125228058:AAG:A	donor_loss	1.0000
9:125228059:AG:A	donor_loss	1.0000
9:125228060:G:GG	donor_gain	1.0000
9:125228060:GTAAG:G	donor_loss	1.0000
9:125228061:T:A	donor_loss	1.0000
9:125232592:GCA:G	acceptor_loss	1.0000
9:125232593:CAG:C	acceptor_loss	1.0000
9:125232595:G:A	acceptor_loss	1.0000
9:125232595:GGT:G	acceptor_gain	1.0000
9:125232731:ACC:A	donor_gain	1.0000

AlphaMissense

2432 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:125232607:T:A	W230R	0.995
9:125232607:T:C	W230R	0.995
9:125227921:T:A	W180R	0.994
9:125227921:T:C	W180R	0.994
9:125213421:A:T	E88V	0.992
9:125227961:G:C	R193P	0.990
9:125232695:G:A	G259D	0.989
9:125233699:T:A	W280R	0.988
9:125233699:T:C	W280R	0.988
9:125228009:G:A	G209E	0.987
9:125232736:T:G	Y273D	0.985
9:125213472:G:A	G105E	0.984
9:125233739:G:C	R293P	0.984
9:125228012:G:A	G210D	0.983
9:125220591:A:C	R139S	0.982
9:125220591:A:T	R139S	0.982
9:125232695:G:T	G259V	0.982
9:125220550:T:A	W126R	0.981
9:125220550:T:C	W126R	0.981
9:125213475:G:A	G106D	0.980
9:125220635:T:A	V154D	0.980
9:125227967:G:A	G195D	0.979
9:125233922:G:A	G354D	0.979
9:125207676:G:C	A56P	0.978
9:125220644:G:A	G157D	0.978
9:125227997:T:C	L205P	0.978
9:125228009:G:T	G209V	0.978
9:125232609:G:C	W230C	0.978
9:125232609:G:T	W230C	0.978
9:125233745:A:T	D295V	0.978

dbSNP variants (sampled 300 via entrez): RS1000007922 (9:125226726 T>C), RS1000062144 (9:125229861 C>A), RS1000104758 (9:125199896 C>T), RS1000157250 (9:125199718 C>G), RS1000224835 (9:125224215 A>AC), RS1000416075 (9:125212479 A>C,G), RS1000478136 (9:125212055 C>T), RS1000518242 (9:125230285 G>A), RS1000631511 (9:125218005 T>A), RS1000712704 (9:125205444 G>A), RS1000714595 (9:125219741 A>C), RS1000728703 (9:125224235 T>G), RS1000884774 (9:125230729 G>A), RS1000961156 (9:125225199 A>G), RS1000981010 (9:125218251 C>T)

Disease associations

OMIM: gene MIM:605962 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_280	Refractive error	1.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs430397	HSPA5, RABEPK	3	10.50	1	Platinum compounds

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
cotylenin A	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Cycloheximide	affects response to substance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Zidovudine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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