RAVER2

Summary

RAVER2 (ribonucleoprotein, PTB binding 2, HGNC:25577) is a protein-coding gene on chromosome 1p31.3, encoding Ribonucleoprotein PTB-binding 2 (Q9HCJ3). May bind single-stranded nucleic acids.

Enables RNA binding activity. Predicted to be located in cytoplasm and nucleus.

Source: NCBI Gene 55225 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_001366165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25577
Approved symbol	RAVER2
Name	ribonucleoprotein, PTB binding 2
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1579, FLJ10770
Ensembl gene	ENSG00000162437
Ensembl biotype	protein_coding
OMIM	609953
Entrez	55225

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000294428, ENST00000371072, ENST00000418058, ENST00000930905, ENST00000971077, ENST00000971078, ENST00000971079

RefSeq mRNA: 2 — MANE Select: NM_001366165 NM_001366165, NM_018211

CCDS: CCDS41345, CCDS90967

Canonical transcript exons

ENST00000294428 — 12 exons

Exon	Start	End
ENSE00001065196	64789388	64789514
ENSE00001065199	64802976	64803061
ENSE00001065203	64807206	64807474
ENSE00001065207	64804991	64805105
ENSE00001065211	64830839	64833232
ENSE00001179004	64814704	64814840
ENSE00001454278	64804734	64804838
ENSE00001671384	64777623	64778092
ENSE00001681312	64768656	64768722
ENSE00002268413	64745075	64745421
ENSE00003496433	64812738	64812849
ENSE00003507104	64781380	64781571

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 91.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1064 / max 315.6811, expressed in 1550 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3226	5.4299	1377
3227	2.3894	968
3225	1.8321	762
3224	0.4550	275

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	91.94	gold quality
rectum	UBERON:0001052	91.58	gold quality
mucosa of transverse colon	UBERON:0004991	91.22	gold quality
calcaneal tendon	UBERON:0003701	88.39	gold quality
jejunum	UBERON:0002115	87.78	gold quality
transverse colon	UBERON:0001157	86.67	gold quality
ventricular zone	UBERON:0003053	86.54	gold quality
ileal mucosa	UBERON:0000331	86.35	gold quality
colonic mucosa	UBERON:0000317	86.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.22	gold quality
right coronary artery	UBERON:0001625	85.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.02	gold quality
duodenum	UBERON:0002114	84.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.72	gold quality
tendon	UBERON:0000043	84.70	gold quality
islet of Langerhans	UBERON:0000006	84.66	gold quality
muscle of leg	UBERON:0001383	84.41	gold quality
ganglionic eminence	UBERON:0004023	84.30	gold quality
embryo	UBERON:0000922	84.29	gold quality
ascending aorta	UBERON:0001496	84.14	gold quality
large intestine	UBERON:0000059	84.09	gold quality
thoracic aorta	UBERON:0001515	84.06	gold quality
colon	UBERON:0001155	83.89	gold quality
intestine	UBERON:0000160	83.87	gold quality
minor salivary gland	UBERON:0001830	83.77	gold quality
gastrocnemius	UBERON:0001388	83.74	gold quality
gall bladder	UBERON:0002110	83.63	gold quality
cerebellar hemisphere	UBERON:0002245	83.55	gold quality
cerebellar cortex	UBERON:0002129	83.47	gold quality
left coronary artery	UBERON:0001626	83.41	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.81
E-GEOD-100618	no	257.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

142 targeting RAVER2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-374A-5P	99.90	71.34	2923

Literature-anchored findings (GeneRIF, showing 3)

• Together, our results suggest that regulation of human Raver2 expression involves TATA-less transcriptional activity. (PMID:22146317)
• genetic polymorphism is ssociated with increased susceptibility for ulcerative colitis (PMID:22561236)
• Deregulation of LMNB1 expression induces modified splicing of several genes, likely driven by raver-2 overexpression, and suggest that an alteration of mRNA processing could be a pathogenic mechanism in adult-onset autosomal dominant leukodystrophy. (PMID:25637521)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	raver2	ENSDARG00000075034
mus_musculus	Raver2	ENSMUSG00000035275
rattus_norvegicus	Raver2	ENSRNOG00000023812
drosophila_melanogaster	nonA	FBGN0004227
drosophila_melanogaster	nonA-l	FBGN0015520
drosophila_melanogaster	nito	FBGN0027548

Paralogs (7): SPEN (ENSG00000065526), SFPQ (ENSG00000116560), PSPC1 (ENSG00000121390), NONO (ENSG00000147140), RAVER1 (ENSG00000161847), RBM15 (ENSG00000162775), RBM15B (ENSG00000259956)

Protein

Protein identifiers

Ribonucleoprotein PTB-binding 2 — Q9HCJ3 (reviewed: Q9HCJ3)

Alternative names: Protein raver-2

All UniProt accessions (2): E9PE10, Q9HCJ3

UniProt curated annotations — full annotation on UniProt →

Function. May bind single-stranded nucleic acids.

Subunit / interactions. Interacts with PTBP1 and RAVER1.

Subcellular location. Nucleus. Cytoplasm.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HCJ3-1	1	yes
Q9HCJ3-2	2

RefSeq proteins (2): NP_001353094, NP_060681 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034636	RAVER2_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR047942	RAVER2_RRM3	Domain
IPR047943	RAVER2_RRM1	Domain
IPR050502	Euk_RNA-bind_prot	Family

Pfam: PF00076

UniProt features (20 total): strand 5, helix 3, domain 3, region of interest 3, compositionally biased region 2, initiator methionine 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1WG1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCJ3-F1	62.10	0.36

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

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): AAGCAAT_MIR137, WANG_CLIM2_TARGETS_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, TGCCTTA_MIR124A, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, LIU_PROSTATE_CANCER_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, BILANGES_SERUM_SENSITIVE_GENES, BILANGES_SERUM_RESPONSE_TRANSLATION, PRC2_SUZ12_UP.V1_DN, FOXN3_TARGET_GENES, ZNF282_TARGET_GENES, ZNF563_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (2): RNA binding (GO:0003723), nucleic acid binding (GO:0003676)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAVER2	PTBP1	P26599	724
RAVER2	HNRNPDL	O14979	715
RAVER2	HNRNPC	P07910	654
RAVER2	KHSRP	Q92945	606
RAVER2	CELF1	Q92879	593
RAVER2	PTBP3	O95758	588
RAVER2	PTBP2	Q9UKA9	558
RAVER2	RRM2	P31350	533
RAVER2	CACHD1	Q5VU97	517
RAVER2	NOVA1	P51513	468
RAVER2	NUCLEOLIN	P19338	438
RAVER2	RAVER1	Q8IY67	407
RAVER2	NONO	P30807	389
RAVER2	VXN	Q8TAG6	348
RAVER2	FYB2	Q5VWT5	348
RAVER2	EFCAB7	A8K855	348

IntAct

7 interactions, top by confidence:

A	B	Type	Score
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
TIMM8A	MT-ATP8	psi-mi:“MI:0914”(association)	0.350
SPATA20	HDAC4	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Proximity Label-MS), RAVER2 (Proximity Label-MS), RAVER2 (Proximity Label-MS), RAVER2 (Proximity Label-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS), RAVER2 (Affinity Capture-MS)

ESM2 similar proteins: A2A5E6, A5PK23, A6NKF2, A6PWV5, E9QEA3, G5E5X0, O15353, O70405, O75385, O95402, P0C0T2, P20823, P50548, P55198, P70459, P78411, Q04888, Q3B8N7, Q5I1X5, Q5XI28, Q63HR2, Q6BCB4, Q6GQX6, Q7TN02, Q7TPD6, Q80VC9, Q80WC3, Q8C2B3, Q8CGB6, Q8IVH2, Q8IY67, Q8K4J6, Q8NBF1, Q8TDD2, Q8VD12, Q8VDL9, Q8VI67, Q8WUF5, Q8WUI4, Q91474

Diamond homologs: A4QNI8, A7SKE9, B5DF91, O09032, O75821, P26378, P70372, P90727, P90978, Q12926, Q15717, Q28CY2, Q28FX0, Q28GD4, Q3SZM1, Q3ZC12, Q5R9Z6, Q5RK09, Q5U259, Q5XI28, Q60899, Q61701, Q641B2, Q6DJI8, Q6DRC4, Q6GLB5, Q7SYS2, Q7SZT7, Q7TPD6, Q8CH84, Q8IY67, Q9BYG3, Q9CW46, Q9HCJ3, Q9P6M8, Q9Z1D1, A8WLV5, P78795, Q19706, Q8BHN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2307 predictions. Top by Δscore:

Variant	Effect	Δscore
1:64745418:CCAG:C	donor_loss	1.0000
1:64745419:CAGGT:C	donor_loss	1.0000
1:64745420:AG:A	donor_loss	1.0000
1:64745421:GG:G	donor_loss	1.0000
1:64745422:G:C	donor_loss	1.0000
1:64768650:TTTCA:T	acceptor_loss	1.0000
1:64768652:TCA:T	acceptor_loss	1.0000
1:64768653:CAG:C	acceptor_loss	1.0000
1:64768654:A:AC	acceptor_loss	1.0000
1:64768654:A:AG	acceptor_gain	1.0000
1:64768654:AG:A	acceptor_gain	1.0000
1:64768655:G:GG	acceptor_gain	1.0000
1:64768655:GG:G	acceptor_gain	1.0000
1:64768655:GGA:G	acceptor_gain	1.0000
1:64768655:GGAA:G	acceptor_gain	1.0000
1:64768722:GGTAA:G	donor_loss	1.0000
1:64768723:G:GA	donor_loss	1.0000
1:64768724:T:G	donor_loss	1.0000
1:64781567:GTGTG:G	donor_gain	1.0000
1:64781568:TGTGG:T	donor_loss	1.0000
1:64781570:TGG:T	donor_loss	1.0000
1:64781572:G:C	donor_loss	1.0000
1:64781572:G:GG	donor_gain	1.0000
1:64781573:TAA:T	donor_loss	1.0000
1:64789376:T:G	acceptor_gain	1.0000
1:64789377:A:AG	acceptor_gain	1.0000
1:64789381:A:AG	acceptor_gain	1.0000
1:64789384:GCAG:G	acceptor_loss	1.0000
1:64789385:CA:C	acceptor_loss	1.0000
1:64789386:A:AC	acceptor_loss	1.0000

AlphaMissense

4492 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:64777629:T:A	V108D	1.000
1:64777710:T:A	V135D	1.000
1:64745378:G:T	R69M	0.999
1:64777623:C:A	A106D	0.999
1:64777635:T:C	L110S	0.999
1:64777863:G:A	G186E	0.999
1:64777893:C:A	A196D	0.999
1:64745378:G:C	R69T	0.998
1:64745379:G:C	R69S	0.998
1:64745379:G:T	R69S	0.998
1:64768722:G:C	A106P	0.998
1:64777625:T:C	F107L	0.998
1:64777627:T:A	F107L	0.998
1:64777627:T:G	F107L	0.998
1:64777653:C:A	A116D	0.998
1:64777866:T:C	F187S	0.998
1:64777874:T:C	Y190H	0.998
1:64777874:T:G	Y190D	0.998
1:64777875:A:C	Y190S	0.998
1:64777881:A:T	K192I	0.998
1:64745384:T:C	I71T	0.997
1:64745384:T:G	I71S	0.997
1:64745387:T:C	L72P	0.997
1:64745399:T:C	L76P	0.997
1:64768672:T:C	L89S	0.997
1:64777737:T:C	L144S	0.997
1:64777791:T:A	V162D	0.997
1:64777803:G:A	G166E	0.997
1:64777803:G:T	G166V	0.997
1:64777995:C:T	S230F	0.997

dbSNP variants (sampled 300 via entrez): RS1000072365 (1:64822736 C>G), RS1000102834 (1:64763603 A>C,G), RS1000126455 (1:64792831 A>G,T), RS1000127039 (1:64746850 G>A), RS1000166174 (1:64746525 C>T), RS1000212923 (1:64754082 G>A), RS1000234672 (1:64794215 G>A,T), RS1000302207 (1:64825778 G>A), RS1000380232 (1:64809379 G>A,T), RS1000384208 (1:64816518 T>C), RS1000386784 (1:64819266 T>G), RS1000405897 (1:64826017 A>G), RS1000420857 (1:64818954 A>G), RS1000444383 (1:64801739 C>T), RS1000551887 (1:64755736 T>G)

Disease associations

OMIM: gene MIM:609953 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004347_15	Glioma	4.000000e-09
GCST004349_12	Glioblastoma	2.000000e-09
GCST004606_183	Eosinophil count	7.000000e-10
GCST005931_1	Glioma	1.000000e-06
GCST005932_13	Glioblastoma	3.000000e-06
GCST010571_5	Autoimmune thyroid disease	5.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count

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
rs72675408	RAVER2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
corosolic 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	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Dasatinib	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1

Clinical trials (associated diseases)

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