REP15

Summary

REP15 (RAB15 effector protein, HGNC:33748) is a protein-coding gene on chromosome 12p11.22, encoding Rab15 effector protein (Q6BDI9). Effector that interacts with Rab GTPases in their active form (GTP-bound) including RAB15, RAB3A-D and RAB34.

The protein encoded by this intronless gene interacts with GTP-bound Rab15 and is involved in recycling of transferrin receptor from the endocytic recycling compartment to the cell surface.

Source: NCBI Gene 387849 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001029874

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33748
Approved symbol	REP15
Name	RAB15 effector protein
Location	12p11.22
Locus type	gene with protein product
Status	Approved
Aliases	RAB15EP
Ensembl gene	ENSG00000174236
Ensembl biotype	protein_coding
OMIM	610848
Entrez	387849

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000310791

RefSeq mRNA: 1 — MANE Select: NM_001029874 NM_001029874

CCDS: CCDS31762

Canonical transcript exons

ENST00000310791 — 1 exons

Exon	Start	End
ENSE00001188797	27696447	27697596

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 94.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0414 / max 16.6857, expressed in 10 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124843	0.0414	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	94.65	gold quality
rectum	UBERON:0001052	93.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.00	gold quality
transverse colon	UBERON:0001157	85.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.10	silver quality
duodenum	UBERON:0002114	83.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.63	gold quality
small intestine	UBERON:0002108	80.85	gold quality
body of stomach	UBERON:0001161	80.19	gold quality
stomach	UBERON:0000945	77.85	gold quality
intestine	UBERON:0000160	77.77	gold quality
fundus of stomach	UBERON:0001160	77.54	gold quality
colon	UBERON:0001155	76.64	gold quality
heart left ventricle	UBERON:0002084	74.23	gold quality
apex of heart	UBERON:0002098	72.35	gold quality
colonic epithelium	UBERON:0000397	71.82	gold quality
mucosa of stomach	UBERON:0001199	71.52	gold quality
heart	UBERON:0000948	69.56	gold quality
vermiform appendix	UBERON:0001154	69.34	gold quality
thoracic aorta	UBERON:0001515	68.02	gold quality
right lobe of liver	UBERON:0001114	67.96	gold quality
descending thoracic aorta	UBERON:0002345	67.94	gold quality
ascending aorta	UBERON:0001496	67.92	gold quality
lower esophagus mucosa	UBERON:0035834	67.42	gold quality
smooth muscle tissue	UBERON:0001135	67.14	gold quality
stromal cell of endometrium	CL:0002255	66.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.11	gold quality
placenta	UBERON:0001987	65.57	gold quality
spleen	UBERON:0002106	64.95	gold quality
ovary	UBERON:0000992	64.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	33.20
E-MTAB-8410	yes	17.43
E-ANND-3	no	2.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting REP15, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-4501	98.72	67.19	921
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-1322	97.98	68.96	625
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-3683	91.74	64.69	58

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rep15	ENSMUSG00000040121
rattus_norvegicus	Rep15	ENSRNOG00000001840

Protein

Protein identifiers

Rab15 effector protein — Q6BDI9 (reviewed: Q6BDI9)

All UniProt accessions (1): Q6BDI9

UniProt curated annotations — full annotation on UniProt →

Function. Effector that interacts with Rab GTPases in their active form (GTP-bound) including RAB15, RAB3A-D and RAB34. Controls downstream signaling such as cell proliferation and cell migration. Also regulates transferrin receptor recycling from the endocytic recycling compartment.

Subunit / interactions. Interacts with the GTP-bound form of RAB15, RAB3A-D and RAB34.

Subcellular location. Early endosome membrane.

RefSeq proteins (1): NP_001025045* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027985	Rab15_effector	Domain

Pfam: PF15208

UniProt features (35 total): mutagenesis site 9, strand 8, helix 7, turn 4, sequence conflict 2, sequence variant 2, initiator methionine 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8A4A	X-RAY DIFFRACTION	2.52
8A4C	X-RAY DIFFRACTION	2.75
8A4B	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6BDI9-F1	81.04	0.48

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): 2

Mutagenesis-validated functional residues (9):

Position	Phenotype
140	no change in binding affinity with rab3a.
154	loss of interaction with rab3a; when associated with a-155.
155	loss of interaction with rab3a; when associated with a-154.
158	decreased interaction with rab3a.
84	no change in binding affinity with rab3a. loss of interaction with rab3a; when associated with a-85.
85	decreased interaction with rab3a. loss of interaction with rab3a; when associated with a-84.
88	decreased interaction with rab3a.
107	loss of interaction with rab3a.
135	no change in binding affinity with rab3a.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 53 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_IRON_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, chr12p11, GOBP_RECEPTOR_METABOLIC_PROCESS, GOCC_EARLY_ENDOSOME_MEMBRANE, GOCC_RECYCLING_ENDOSOME, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_RECEPTOR_RECYCLING, GOBP_TRANSFERRIN_TRANSPORT, FEVR_CTNNB1_TARGETS_UP, GOCC_ENDOSOME_MEMBRANE, MIR4795_3P

GO Biological Process (2): receptor recycling (GO:0001881), transferrin transport (GO:0033572)

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

GO Cellular Component (6): endosome membrane (GO:0010008), early endosome membrane (GO:0031901), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), endosome (GO:0005768), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome	2
cellular anatomical structure	2
endocytosis	1
receptor metabolic process	1
iron ion transport	1
protein transport	1
binding	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
early endosome	1
endosome membrane	1
cytoplasm	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
REP15	RAB15	P59190	884
REP15	EEA1	Q15075	668
REP15	RAB11A	P24410	581
REP15	UBXN8	O00124	581
REP15	TFRC	P02786	558
REP15	CHML	P26374	541
REP15	RAB5A	P20339	525
REP15	SAMD13	Q5VXD3	506
REP15	NXPE4	Q6UWF7	479
REP15	CHM	P24386	433
REP15	ZNF556	Q9HAH1	431
REP15	RFESD	Q8TAC1	417
REP15	REXO5	Q96IC2	402
REP15	ZNF726	A6NNF4	400
REP15	RAB22A	Q9UL26	396

IntAct

19 interactions, top by confidence:

A	B	Type	Score
EVI5	REP15	psi-mi:“MI:0915”(physical association)	0.670
ZRSR2P1	REP15	psi-mi:“MI:0915”(physical association)	0.560
REP15	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
GNG11	REP15	psi-mi:“MI:0915”(physical association)	0.560
ZRSR2	REP15	psi-mi:“MI:0915”(physical association)	0.560
REP15	MCM3AP	psi-mi:“MI:0914”(association)	0.350
REP15	EVI5	psi-mi:“MI:0915”(physical association)	0.000
ZRSR2P1	REP15	psi-mi:“MI:0915”(physical association)	0.000
ARID3A	REP15	psi-mi:“MI:0915”(physical association)	0.000
GNG11	REP15	psi-mi:“MI:0915”(physical association)	0.000
ZRSR2	REP15	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): REP15 (Positive Genetic), REP15 (Two-hybrid), REP15 (Two-hybrid), REP15 (Two-hybrid), REP15 (Two-hybrid), ZRSR1 (Two-hybrid), GDAP2 (Affinity Capture-MS), C1orf198 (Affinity Capture-MS), CEP250 (Affinity Capture-MS), TLK2 (Affinity Capture-MS), ZC2HC1B (Affinity Capture-MS), MCM3AP (Affinity Capture-MS), NEK1 (Affinity Capture-MS), SLC4A2 (Affinity Capture-MS), EVI5 (Affinity Capture-MS)

ESM2 similar proteins: A1A4P9, A4QNG1, B1WB06, B8JLV7, F4HVW5, F4IRM4, F4J264, F4JTI1, K7TQE3, O48781, O65573, O80462, O81893, O82387, Q0IY07, Q0WPN7, Q3EBL9, Q3KPR1, Q3ZBK3, Q5BK13, Q5M7V7, Q5M856, Q5MK23, Q5MK24, Q5RHZ2, Q6BDI9, Q6E7H0, Q7X6P3, Q7ZYB4, Q84JN1, Q84M47, Q84WF5, Q8IYF3, Q8L7N4, Q8LBH4, Q8RXH2, Q8S9J3, Q8W032, Q8W4F0, Q94BM7

Diamond homologs: Q6BDI9, Q9D7T1

SIGNOR signaling

0 interactions.

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	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

295 predictions. Top by Δscore:

Variant	Effect	Δscore
12:27696926:GAATC:G	donor_gain	0.7200
12:27697007:G:GT	donor_gain	0.6200
12:27696670:G:GT	donor_gain	0.6100
12:27696930:C:G	donor_gain	0.6100
12:27696631:G:GA	donor_gain	0.6000
12:27696990:G:GG	donor_gain	0.6000
12:27696930:C:CG	donor_gain	0.5900
12:27696989:A:AG	donor_gain	0.5900
12:27697388:ATT:A	acceptor_gain	0.5800
12:27696630:T:TA	donor_gain	0.5700
12:27696698:A:G	donor_gain	0.5700
12:27696999:A:G	donor_gain	0.5700
12:27697030:A:T	donor_gain	0.5600
12:27697290:G:GG	donor_gain	0.5600
12:27696965:G:T	donor_gain	0.5500
12:27696670:GGA:G	donor_gain	0.5400
12:27696671:GAG:G	donor_gain	0.5400
12:27696699:G:GG	donor_gain	0.5400
12:27696982:G:GT	donor_gain	0.5400
12:27697072:A:T	donor_gain	0.5400
12:27697390:T:A	acceptor_gain	0.5400
12:27697181:GATT:G	donor_gain	0.5100
12:27697240:AGAG:A	donor_loss	0.5100
12:27697242:AG:A	donor_loss	0.5100
12:27697243:GGTG:G	donor_loss	0.5100
12:27697244:G:C	donor_loss	0.5100
12:27697245:T:G	donor_loss	0.5100
12:27696632:G:GG	donor_gain	0.5000
12:27697071:G:GT	donor_gain	0.4900
12:27696985:GAAAA:G	donor_gain	0.4800

AlphaMissense

1560 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:27697013:T:C	F151L	0.967
12:27697015:C:A	F151L	0.967
12:27697015:C:G	F151L	0.967
12:27696839:T:A	W93R	0.965
12:27696839:T:C	W93R	0.965
12:27696845:T:A	W95R	0.936
12:27696845:T:C	W95R	0.936
12:27696654:C:A	A31E	0.922
12:27697163:T:C	F201L	0.920
12:27697165:T:A	F201L	0.920
12:27697165:T:G	F201L	0.920
12:27696841:G:C	W93C	0.917
12:27696841:G:T	W93C	0.917
12:27696737:T:C	F59L	0.912
12:27696739:C:A	F59L	0.912
12:27696739:C:G	F59L	0.912
12:27696888:C:A	A109E	0.902
12:27697037:T:C	C159R	0.899
12:27696656:G:C	A32P	0.898
12:27696891:T:A	V110E	0.890
12:27697095:T:A	V178D	0.886
12:27697039:C:G	C159W	0.884
12:27697047:T:C	L162P	0.883
12:27697043:G:C	G161R	0.881
12:27697167:T:A	V202D	0.878
12:27696738:T:C	F59S	0.875
12:27696805:G:A	M81I	0.875
12:27696805:G:C	M81I	0.875
12:27696805:G:T	M81I	0.875
12:27697091:G:A	G177R	0.874

dbSNP variants (sampled 300 via entrez): RS1000292166 (12:27695265 T>C), RS1002957214 (12:27696892 A>G), RS1003544705 (12:27697752 T>C), RS1003596963 (12:27697976 G>C,T), RS1004034352 (12:27696200 A>G), RS1005712294 (12:27694813 G>A), RS1006544642 (12:27694748 C>T), RS1008591422 (12:27697413 C>G,T), RS1009073145 (12:27697840 A>T), RS1010754529 (12:27695475 A>G), RS1014305488 (12:27694542 C>T), RS1014398654 (12:27694941 A>G), RS1015067582 (12:27697880 T>A), RS1015385278 (12:27696206 C>T), RS1015395046 (12:27696520 G>A)

Disease associations

OMIM: gene MIM:610848 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	affects expression, decreases expression	2
bisphenol A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
abrine	decreases expression	1
Sunitinib	decreases expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Disulfiram	affects binding, decreases expression	1
Estradiol	affects expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Niclosamide	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Okadaic Acid	increases expression	1
Nanotubes, Carbon	increases expression	1

Clinical trials (associated diseases)

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