RUFY2

Summary

RUFY2 (RUN and FYVE domain containing 2, HGNC:19761) is a protein-coding gene on chromosome 10q21.3, encoding RUN and FYVE domain-containing protein 2 (Q8WXA3).

Enables SH3 domain binding activity. Predicted to be involved in regulation of endocytosis. Located in cytoplasm.

Source: NCBI Gene 55680 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_001330103

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19761
Approved symbol	RUFY2
Name	RUN and FYVE domain containing 2
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	RABIP4R, FLJ10063, KIAA1537, ZFYVE13
Ensembl gene	ENSG00000204130
Ensembl biotype	protein_coding
OMIM	610328
Entrez	55680

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000265865, ENST00000342616, ENST00000388768, ENST00000399200, ENST00000454950, ENST00000463210, ENST00000466187, ENST00000466493, ENST00000472394, ENST00000473398, ENST00000484083, ENST00000491118, ENST00000602465, ENST00000879982, ENST00000879983, ENST00000879984, ENST00000879985, ENST00000879986, ENST00000937697, ENST00000937698, ENST00000937699, ENST00000969076, ENST00000969077

RefSeq mRNA: 4 — MANE Select: NM_001330103 NM_001042417, NM_001278225, NM_001330103, NM_017987

CCDS: CCDS41534, CCDS44414, CCDS60544, CCDS81470

Canonical transcript exons

ENST00000602465 — 18 exons

Exon	Start	End
ENSE00001503896	68376853	68376972
ENSE00001503897	68379424	68379521
ENSE00001503901	68386059	68386128
ENSE00003249606	68407186	68407277
ENSE00003412445	68343408	68345911
ENSE00003467592	68381232	68381399
ENSE00003472714	68394075	68394136
ENSE00003478143	68383798	68383914
ENSE00003523529	68355353	68355401
ENSE00003577377	68384051	68384152
ENSE00003598945	68404671	68404844
ENSE00003626278	68346007	68346084
ENSE00003627066	68363590	68363684
ENSE00003627892	68393138	68393203
ENSE00003652496	68396780	68396881
ENSE00003652986	68363984	68364113
ENSE00003663211	68394328	68394451
ENSE00003681692	68401620	68401737

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1260 / max 315.7795, expressed in 1780 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109757	10.7922	1769
109756	1.1023	694
109754	0.7706	285
109753	0.3640	156
109755	0.0969	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.02	gold quality
cerebellar hemisphere	UBERON:0002245	94.98	gold quality
cerebellar cortex	UBERON:0002129	94.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.88	gold quality
tendon	UBERON:0000043	93.54	gold quality
cortical plate	UBERON:0005343	93.38	gold quality
cerebellum	UBERON:0002037	92.59	gold quality
tendon of biceps brachii	UBERON:0008188	92.38	gold quality
sural nerve	UBERON:0015488	91.60	gold quality
spinal cord	UBERON:0002240	91.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.20	gold quality
right frontal lobe	UBERON:0002810	89.84	gold quality
ganglionic eminence	UBERON:0004023	89.20	gold quality
embryo	UBERON:0000922	89.19	gold quality
prefrontal cortex	UBERON:0000451	89.03	gold quality
colonic epithelium	UBERON:0000397	89.01	gold quality
ventricular zone	UBERON:0003053	88.31	gold quality
anterior cingulate cortex	UBERON:0009835	88.24	gold quality
hypothalamus	UBERON:0001898	88.08	gold quality
adrenal tissue	UBERON:0018303	86.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.50	gold quality
left ovary	UBERON:0002119	86.41	gold quality
right uterine tube	UBERON:0001302	86.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.98	gold quality
right ovary	UBERON:0002118	85.92	gold quality
amygdala	UBERON:0001876	85.81	gold quality
medial globus pallidus	UBERON:0002477	85.65	gold quality
tibial nerve	UBERON:0001323	85.21	gold quality
neocortex	UBERON:0001950	85.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	7.00
E-ANND-3	yes	5.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

185 targeting RUFY2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-590-3P	99.96	74.34	6478

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rufy2	ENSDARG00000062019
mus_musculus	Rufy2	ENSMUSG00000020070
rattus_norvegicus	Rufy2	ENSRNOG00000065563
drosophila_melanogaster	CG6051	FBGN0039492
drosophila_melanogaster	CG31064	FBGN0051064
caenorhabditis_elegans		WBGENE00003084

Paralogs (13): RUFY3 (ENSG00000018189), ZFYVE16 (ENSG00000039319), SNX29 (ENSG00000048471), ZFYVE26 (ENSG00000072121), RUNDC3B (ENSG00000105784), RUNDC3A (ENSG00000108309), PLEKHM2 (ENSG00000116786), ZFYVE28 (ENSG00000159733), ZFYVE1 (ENSG00000165861), ZFYVE19 (ENSG00000166140), PLEKHF1 (ENSG00000166289), PLEKHF2 (ENSG00000175895), RUFY1 (ENSG00000176783)

Protein

Protein identifiers

RUN and FYVE domain-containing protein 2 — Q8WXA3 (reviewed: Q8WXA3)

Alternative names: Rab4-interacting protein related

All UniProt accessions (3): Q8WXA3, H0YD93, S4R3P2

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with BMX.

Subcellular location. Nucleus.

Tissue specificity. Expressed in brain, lung and testis.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8WXA3-2	1	yes
Q8WXA3-1	5
Q8WXA3-3	2
Q8WXA3-4	3
Q8WXA3-5	4

RefSeq proteins (4): NP_001035882, NP_001265154, NP_001317032, NP_060457 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000306	Znf_FYVE	Domain
IPR004012	Run_dom	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017455	Znf_FYVE-rel	Domain
IPR037213	Run_dom_sf	Homologous_superfamily
IPR047332	RUN_RUFY2	Domain
IPR047333	FYVE_RUFY2	Domain
IPR047335	RUFY1-3	Family

Pfam: PF01363, PF02759

UniProt features (19 total): binding site 8, splice variant 6, chain 1, domain 1, sequence variant 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXA3-F1	82.05	0.40

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 (8): 590; 593; 546; 549; 562; 565; 570; 573

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): chr10q21, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, WANG_LMO4_TARGETS_DN, GOBP_REGULATION_OF_ENDOCYTOSIS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_REGULATION_OF_TRANSPORT, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, JOHNSTONE_PARVB_TARGETS_3_DN, E2F3_UP.V1_DN, JAK2_DN.V1_DN, GSE5503_MLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_UP, GSE14415_FOXP3_KO_NATURAL_TREG_VS_TCONV_UP, GSE13547_WT_VS_ZFX_KO_BCELL_UP

GO Biological Process (1): regulation of endocytosis (GO:0030100)

GO Molecular Function (4): zinc ion binding (GO:0008270), SH3 domain binding (GO:0017124), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
transition metal ion binding	1
protein domain specific binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RUFY2	EPHA3	P29320	884
RUFY2	RUFY4	Q6ZNE9	683
RUFY2	FRMD4A	Q9P2Q2	583
RUFY2	MYO5C	Q9NQX4	573
RUFY2	PBLD	P30039	538
RUFY2	RAB33A	Q14088	529
RUFY2	BMX	P51813	524
RUFY2	RET	P07949	523
RUFY2	CLIP1	P30622	513
RUFY2	ERC1	Q8IUD2	512
RUFY2	RELCH	Q9P260	506
RUFY2	RET	P07949	503
RUFY2	EML4	Q9HC35	452
RUFY2	NCOA4	Q13772	452
RUFY2	KIF5B	P33176	424

IntAct

46 interactions, top by confidence:

A	B	Type	Score
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
P2RY10	ATM	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
EEA1	IGF2R	psi-mi:“MI:2364”(proximity)	0.450
RUFY2	DUSP23	psi-mi:“MI:0915”(physical association)	0.370
RUFY2	SF3B3	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
	FAM171A2	psi-mi:“MI:0914”(association)	0.350
GYPA	HYKK	psi-mi:“MI:0914”(association)	0.350
LAGE3	HYKK	psi-mi:“MI:0914”(association)	0.350
NPTN	RTL8C	psi-mi:“MI:0914”(association)	0.350
SYCE1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
CEP170P1	DAPK3	psi-mi:“MI:0914”(association)	0.350
TPM1	SPAG9	psi-mi:“MI:0914”(association)	0.350
RUFY2	RUFY3	psi-mi:“MI:0914”(association)	0.350
RUFY1	GRK6	psi-mi:“MI:0914”(association)	0.350
CD80	RIMOC1	psi-mi:“MI:0914”(association)	0.350
CXCR3	RIMOC1	psi-mi:“MI:0914”(association)	0.350
FARSA	VWA8	psi-mi:“MI:0914”(association)	0.350
GPR17	C1QTNF9B	psi-mi:“MI:0914”(association)	0.350
MICB	LGALS8	psi-mi:“MI:0914”(association)	0.350
NPTN	RIMOC1	psi-mi:“MI:0914”(association)	0.350
P2RY8	CIT	psi-mi:“MI:0914”(association)	0.350
SPINT2	SPAG9	psi-mi:“MI:0914”(association)	0.350
TNFRSF9	SCO1	psi-mi:“MI:0914”(association)	0.350

BioGRID (58): RUFY2 (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), PURB (Co-fractionation), RUFY2 (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), RUFY1 (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), RUFY2 (Affinity Capture-MS), RUFY3 (Affinity Capture-MS), RUFY2 (Proximity Label-MS), RUFY2 (Proximity Label-MS), RUFY2 (Two-hybrid), RUFY2 (Two-hybrid)

ESM2 similar proteins: A0PJP4, A0PJT0, A2VDP1, A4IFK7, D3ZUQ0, E9PSL7, O14578, O75665, P0C219, P49025, P97817, Q01850, Q0IHE5, Q14BN4, Q17QG3, Q28623, Q3LGD4, Q3SYW5, Q3URD3, Q3V079, Q4R3X1, Q4R7Y8, Q58A65, Q5DTM8, Q5EBL4, Q5R5R4, Q5VTR2, Q5ZJA3, Q5ZLS3, Q62172, Q62796, Q68CZ1, Q6AYA0, Q6DFC2, Q6DH86, Q6NRH3, Q6ZUS6, Q7Z3E2, Q86VS8, Q8BR07

Diamond homologs: A0A0D1E015, A0JMD2, A1CEK1, A1DFP5, A2QWA2, A4QTV1, A8QCE4, A8XJZ8, B0G126, B0WAQ0, B3MT31, B3P851, B4G2G5, B4IC49, B4JHI7, B4K982, B4M140, B4NFJ7, B4PRU6, D2H5P6, D3ZVP7, D4A8G9, E1BLZ4, F1MM41, F7EP40, O13821, O14964, O59722, O76902, O95405, O96838, P0CS26, P0CS27, P34756, P40343, Q05B78, Q08CN9, Q0CJV3, Q0P4S0, Q0U4Z8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3359 predictions. Top by Δscore:

Variant	Effect	Δscore
10:68341169:TTTA:T	acceptor_loss	1.0000
10:68341171:TAGTT:T	acceptor_loss	1.0000
10:68341172:A:AG	acceptor_gain	1.0000
10:68341172:AGT:A	acceptor_loss	1.0000
10:68341173:G:GA	acceptor_gain	1.0000
10:68341173:GTT:G	acceptor_gain	1.0000
10:68341173:GTTC:G	acceptor_gain	1.0000
10:68341295:A:G	donor_gain	1.0000
10:68341305:CATGC:C	donor_gain	1.0000
10:68341306:ATGC:A	donor_gain	1.0000
10:68341307:TGC:T	donor_gain	1.0000
10:68341307:TGCGT:T	donor_loss	1.0000
10:68341308:GC:G	donor_gain	1.0000
10:68341308:GCG:G	donor_gain	1.0000
10:68341309:CG:C	donor_loss	1.0000
10:68341310:G:C	donor_loss	1.0000
10:68341310:G:GG	donor_gain	1.0000
10:68341311:TA:T	donor_loss	1.0000
10:68341312:AA:A	donor_loss	1.0000
10:68341581:A:AG	acceptor_gain	1.0000
10:68341582:A:G	acceptor_gain	1.0000
10:68341583:A:AG	acceptor_gain	1.0000
10:68341583:A:T	acceptor_loss	1.0000
10:68341584:G:GG	acceptor_gain	1.0000
10:68341584:GA:G	acceptor_gain	1.0000
10:68341584:GAA:G	acceptor_gain	1.0000
10:68341584:GAAC:G	acceptor_gain	1.0000
10:68341666:G:GT	donor_gain	1.0000
10:68341678:TGGGT:T	donor_loss	1.0000
10:68341679:GG:G	donor_gain	1.0000

AlphaMissense

4018 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:68345812:A:G	C593R	1.000
10:68345820:C:T	C590Y	1.000
10:68345821:A:G	C590R	1.000
10:68345872:A:G	C573R	1.000
10:68345881:A:G	C570R	1.000
10:68345900:T:A	R563S	1.000
10:68345900:T:G	R563S	1.000
10:68345901:C:G	R563T	1.000
10:68345903:A:C	C562W	1.000
10:68345904:C:G	C562S	1.000
10:68345904:C:T	C562Y	1.000
10:68345905:A:G	C562R	1.000
10:68345905:A:T	C562S	1.000
10:68345906:G:C	H561Q	1.000
10:68345906:G:T	H561Q	1.000
10:68345908:G:C	H561D	1.000
10:68345911:G:C	H560D	1.000
10:68346010:T:A	R558S	1.000
10:68346010:T:G	R558S	1.000
10:68346025:G:C	F553L	1.000
10:68346025:G:T	F553L	1.000
10:68346027:A:G	F553L	1.000
10:68346046:A:C	C546W	1.000
10:68346047:C:G	C546S	1.000
10:68346048:A:G	C546R	1.000
10:68346048:A:T	C546S	1.000
10:68346073:C:A	W537C	1.000
10:68346073:C:G	W537C	1.000
10:68346075:A:G	W537R	1.000
10:68346075:A:T	W537R	1.000

dbSNP variants (sampled 300 via entrez): RS1000104908 (10:68402539 G>A,C), RS1000151686 (10:68343839 T>A,C), RS1000204789 (10:68373831 C>T), RS1000219511 (10:68390965 C>T), RS1000228767 (10:68359392 G>A), RS1000273245 (10:68390594 G>A), RS1000276022 (10:68344615 G>A), RS1000321301 (10:68373415 C>A,T), RS1000367362 (10:68346180 T>A,C), RS1000431133 (10:68367350 C>A,T), RS1000528597 (10:68370361 T>C), RS1000529353 (10:68377969 T>C), RS1000583172 (10:68377442 C>T), RS1000605875 (10:68374545 T>A), RS1000695437 (10:68407469 C>T)

Disease associations

OMIM: gene MIM:610328 | 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
GCST90020028_50	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

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
rs7917432	ABCC2, RUFY2	3	2.00	1	tenofovir

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
methylmercuric chloride	decreases expression, increases expression	3
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	decreases expression, increases expression, affects cotreatment	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects methylation	1
trichostatin A	decreases expression, increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Manganese	increases abundance, increases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	increases abundance, affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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