EVI5L

Summary

EVI5L (ecotropic viral integration site 5 like, HGNC:30464) is a protein-coding gene on chromosome 19p13.2, encoding EVI5-like protein (Q96CN4). Functions as a GTPase-activating protein (GAP) with a broad specificity.

Enables GTPase activator activity and small GTPase binding activity. Involved in negative regulation of cilium assembly and positive regulation of GTPase activity. Predicted to be located in membrane.

Source: NCBI Gene 115704 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_001159944

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30464
Approved symbol	EVI5L
Name	ecotropic viral integration site 5 like
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000142459
Ensembl biotype	protein_coding
Entrez	115704

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000270530, ENST00000538904, ENST00000597440, ENST00000599036, ENST00000600802, ENST00000601766, ENST00000601984, ENST00000871230, ENST00000871231, ENST00000871232, ENST00000871233, ENST00000962890, ENST00000962891, ENST00000962892, ENST00000962893, ENST00000962894, ENST00000962895, ENST00000962896, ENST00000962897, ENST00000962898, ENST00000962899, ENST00000962900

RefSeq mRNA: 2 — MANE Select: NM_001159944 NM_001159944, NM_145245

CCDS: CCDS12188, CCDS54209

Canonical transcript exons

ENST00000538904 — 20 exons

Exon	Start	End
ENSE00000954339	7848921	7849145
ENSE00001052971	7862388	7862534
ENSE00001052981	7858191	7858331
ENSE00001052986	7847732	7847921
ENSE00001052987	7860561	7860689
ENSE00001052991	7861878	7862018
ENSE00001052992	7862122	7862277
ENSE00001053010	7862972	7863067
ENSE00001053015	7863185	7863280
ENSE00001116077	7863424	7864976
ENSE00001330950	7846496	7846679
ENSE00002211040	7857092	7857124
ENSE00003502915	7849256	7849330
ENSE00003531077	7849997	7850122
ENSE00003564545	7851681	7851770
ENSE00003584213	7853086	7853183
ENSE00003606804	7856015	7856068
ENSE00003684819	7851434	7851577
ENSE00003692211	7853273	7853333
ENSE00003934457	7830218	7830381

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 93.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9324 / max 133.8733, expressed in 1781 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173608	10.5804	1773
173610	0.2182	80
173609	0.1339	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	93.59	gold quality
kidney epithelium	UBERON:0004819	92.86	silver quality
cortical plate	UBERON:0005343	92.81	gold quality
right frontal lobe	UBERON:0002810	92.69	gold quality
anterior cingulate cortex	UBERON:0009835	92.51	gold quality
amygdala	UBERON:0001876	92.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.38	gold quality
frontal cortex	UBERON:0001870	92.09	gold quality
spinal cord	UBERON:0002240	91.90	gold quality
hypothalamus	UBERON:0001898	91.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.76	gold quality
neocortex	UBERON:0001950	91.69	gold quality
substantia nigra	UBERON:0002038	91.56	gold quality
midbrain	UBERON:0001891	91.41	gold quality
putamen	UBERON:0001874	91.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.03	gold quality
cerebral cortex	UBERON:0000956	90.82	gold quality
Ammon’s horn	UBERON:0001954	90.79	gold quality
temporal lobe	UBERON:0001871	90.74	gold quality
inferior vagus X ganglion	UBERON:0005363	90.74	gold quality
ventral tegmental area	UBERON:0002691	90.72	gold quality
subthalamic nucleus	UBERON:0001906	90.49	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.33	gold quality
right testis	UBERON:0004534	90.31	gold quality
left testis	UBERON:0004533	90.14	gold quality
forebrain	UBERON:0001890	90.08	gold quality
nucleus accumbens	UBERON:0001882	89.91	gold quality
caudate nucleus	UBERON:0001873	89.87	gold quality
brain	UBERON:0000955	89.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting EVI5L, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-6805-5P	95.79	64.86	670

Literature-anchored findings (GeneRIF, showing 1)

• Tgifs regulate ciliogenesis and suggests that Evi5l mediates at least part of this effect. (PMID:27956704)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	evi5l	ENSDARG00000052766
mus_musculus	Evi5l	ENSMUSG00000011832
rattus_norvegicus	Evi5l	ENSRNOG00000001034

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), TBC1D22B (ENSG00000065491), TBC1D1 (ENSG00000065882), EVI5 (ENSG00000067208), TBC1D25 (ENSG00000068354), TBC1D2 (ENSG00000095383), TBC1D10A (ENSG00000099992), SGSM3 (ENSG00000100359), TBC1D17 (ENSG00000104946), TBC1D13 (ENSG00000107021), TBC1D12 (ENSG00000108239), TBC1D9 (ENSG00000109436), TBC1D30 (ENSG00000111490), TBC1D15 (ENSG00000121749), TBC1D5 (ENSG00000131374), TBC1D14 (ENSG00000132405), TBC1D8B (ENSG00000133138), TBC1D4 (ENSG00000136111), GRTP1 (ENSG00000139835), SGSM2 (ENSG00000141258), TBCK (ENSG00000145348), USP6NL (ENSG00000148429), RABGAP1L (ENSG00000152061), SGSM1 (ENSG00000167037), TBC1D21 (ENSG00000167139), TBC1D2B (ENSG00000167202), TBC1D16 (ENSG00000167291), TBC1D10B (ENSG00000169221), TBC1D10C (ENSG00000175463), TBC1D28 (ENSG00000189375), TBC1D9B (ENSG00000197226), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

EVI5-like protein — Q96CN4 (reviewed: Q96CN4)

Alternative names: Ecotropic viral integration site 5-like protein

All UniProt accessions (4): Q96CN4, A0A384MR55, M0QYX4, M0R1Y1

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a GTPase-activating protein (GAP) with a broad specificity.

Subunit / interactions. May interact with RAB10.

Domain organisation. The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab’s ‘switch 2’ glutamine and insert in Rab’s active site.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96CN4-1	1	yes
Q96CN4-2	2

RefSeq proteins (2): NP_001153416, NP_660288 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR050302	Rab_GAP_TBC_domain	Family

Pfam: PF00566

UniProt features (13 total): region of interest 3, site 2, coiled-coil region 2, compositionally biased region 2, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CN4-F1	78.50	0.45

Functional residue map

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

Catalytic / active sites (2): 197 (glutamine finger); 156 (arginine finger)

Post-translational modifications (1): 685

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): GCM_GSPT1, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, SP1_Q2_01, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_CILIUM_ORGANIZATION, WTGAAAT_UNKNOWN

GO Biological Process (2): positive regulation of GTPase activity (GO:0043547), negative regulation of cilium assembly (GO:1902018)

GO Molecular Function (3): GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EVI5L	RAB23	Q9ULC3	700
EVI5L	PRR36	Q9H6K5	507
EVI5L	POGK	Q9P215	503
EVI5L	AKAP17A	Q02040	478
EVI5L	MRPL30	Q8TCC3	461
EVI5L	CPLANE2	Q9BU20	420
EVI5L	INTU	Q9ULD6	418
EVI5L	ANKMY1	Q9P2S6	396
EVI5L	FAM72B	Q86X60	364
EVI5L	TBC1D5	Q92609	334
EVI5L	CDC16	Q13042	322
EVI5L	RAB35	Q15286	321
EVI5L	RAB10	P61026	313
EVI5L	TBC1D7	Q9P0N9	306
EVI5L	TGIF2	Q9GZN2	299

IntAct

105 interactions, top by confidence:

A	B	Type	Score
RAB11A	EVI5	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
EVI5L	NUDT18	psi-mi:“MI:0915”(physical association)	0.620
NUDT18	EVI5L	psi-mi:“MI:0915”(physical association)	0.620
OCA2	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
MLH3	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
EVI5L	OCA2	psi-mi:“MI:0915”(physical association)	0.560
EVI5L	MLH3	psi-mi:“MI:0915”(physical association)	0.560
ANKRD36	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
TBC1D21	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
EVI5L	KRT79	psi-mi:“MI:0915”(physical association)	0.560
EVI5L	RBM7	psi-mi:“MI:0915”(physical association)	0.560
GAS8	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
ZNF648	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
CCDC185	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
LNX1	EVI5L	psi-mi:“MI:0915”(physical association)	0.560
EVI5L	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
EVI5L	AP1M1	psi-mi:“MI:0915”(physical association)	0.560
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
FZD10	NRP1	psi-mi:“MI:0914”(association)	0.530
TSPYL1	GPC3	psi-mi:“MI:0914”(association)	0.530

BioGRID (90): EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Two-hybrid), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS), EVI5L (Affinity Capture-MS)

ESM2 similar proteins: A1A5B6, A6H7I8, A7E300, B9VTT2, F1LXF1, M0R7T9, O08873, O14795, O60347, O60447, P0C6S7, P11274, P22681, P22682, P49797, Q0IHY4, Q0VGY8, Q14432, Q3MII6, Q4KUS2, Q5CD77, Q62769, Q69ZT9, Q6A039, Q6F6B3, Q6P9S0, Q6PAJ1, Q6PCS4, Q6ZM89, Q765P7, Q80U28, Q80YA9, Q8BIZ1, Q8CGA2, Q8K214, Q8R1S4, Q8WXG6, Q8WXI2, Q923Q2, Q92625

Diamond homologs: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A2AWA9, A3KGB4, A6H6A9, A6NDS4, A6NER0, A6QP29, B0R0W9, B7ZAP0, B9A6J9, H2KZZ6, O60343, O60447, O95759, O97790, P0C7X1, P35125, P58802, P97366, Q0IIM8, Q10496, Q12317, Q12344, Q28CB1, Q3UYK3, Q4KMP7, Q5R372, Q5RAN1, Q5RCW6, Q5SVR0, Q5TC63, Q5ZJ17, Q60949, Q66K14, Q6DHY5, Q6IPX1, Q6ZT07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3420 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7846676:ACCGG:A	donor_loss	1.0000
19:7846677:CCGGT:C	donor_loss	1.0000
19:7846679:GGT:G	donor_loss	1.0000
19:7846680:G:GG	donor_gain	1.0000
19:7846680:GTG:G	donor_loss	1.0000
19:7846681:T:G	donor_loss	1.0000
19:7847725:T:A	acceptor_gain	1.0000
19:7847729:CA:C	acceptor_loss	1.0000
19:7847730:A:AC	acceptor_loss	1.0000
19:7847730:A:AG	acceptor_gain	1.0000
19:7847731:G:GG	acceptor_gain	1.0000
19:7847731:G:GT	acceptor_loss	1.0000
19:7847903:G:GT	donor_gain	1.0000
19:7847904:A:T	donor_gain	1.0000
19:7848914:T:TA	acceptor_gain	1.0000
19:7848915:G:A	acceptor_gain	1.0000
19:7849122:G:GT	donor_gain	1.0000
19:7849143:AAGG:A	donor_loss	1.0000
19:7849144:AGGTG:A	donor_loss	1.0000
19:7849146:G:GA	donor_loss	1.0000
19:7849147:T:A	donor_loss	1.0000
19:7849254:A:AG	acceptor_gain	1.0000
19:7849255:G:GG	acceptor_gain	1.0000
19:7849328:CAGG:C	donor_loss	1.0000
19:7849329:AGG:A	donor_loss	1.0000
19:7849331:GTA:G	donor_loss	1.0000
19:7849332:T:A	donor_loss	1.0000
19:7849991:CCCTA:C	acceptor_loss	1.0000
19:7849992:CCTA:C	acceptor_loss	1.0000
19:7849994:TA:T	acceptor_loss	1.0000

AlphaMissense

5257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7846652:T:C	L37P	1.000
19:7846655:T:C	L38P	1.000
19:7846664:T:A	L41H	1.000
19:7846664:T:C	L41P	1.000
19:7846673:A:C	Q44P	1.000
19:7847862:T:A	W90R	1.000
19:7847862:T:C	W90R	1.000
19:7848955:G:C	R121P	1.000
19:7848966:T:A	W125R	1.000
19:7848966:T:C	W125R	1.000
19:7848968:G:C	W125C	1.000
19:7848968:G:T	W125C	1.000
19:7849011:T:G	Y140D	1.000
19:7849021:T:C	L143P	1.000
19:7849024:T:A	L144H	1.000
19:7849024:T:C	L144P	1.000
19:7849054:T:A	I154N	1.000
19:7849054:T:C	I154T	1.000
19:7849054:T:G	I154S	1.000
19:7849057:G:C	R155P	1.000
19:7849060:G:C	R156T	1.000
19:7849060:G:T	R156M	1.000
19:7849061:G:C	R156S	1.000
19:7849061:G:T	R156S	1.000
19:7849062:G:C	D157H	1.000
19:7849062:G:T	D157Y	1.000
19:7849063:A:C	D157A	1.000
19:7849063:A:G	D157G	1.000
19:7849063:A:T	D157V	1.000
19:7849064:C:A	D157E	1.000

dbSNP variants (sampled 300 via entrez): RS1000045849 (19:7832809 G>T), RS1000049662 (19:7838964 C>A,G), RS1000102939 (19:7859616 C>T), RS1000124516 (19:7838832 G>A), RS1000228951 (19:7865150 T>C,G), RS1000290591 (19:7844550 C>G), RS1000305067 (19:7863154 C>CT), RS1000397185 (19:7832470 C>T), RS1000463798 (19:7831995 G>T), RS1000566626 (19:7837825 T>C), RS1000577458 (19:7855273 G>A,T), RS1000590671 (19:7854791 G>A), RS1000678661 (19:7844256 C>T), RS1000777403 (19:7842851 CTGAG>C), RS1000784579 (19:7848073 A>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000656_7	HIV-1 viral setpoint	4.000000e-06
GCST002541_116	Menarche (age at onset)	1.000000e-08
GCST90011898_88	Alanine aminotransferase levels	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0004703	age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	decreases expression	1
(+)-JQ1 compound	increases expression	1
Temozolomide	decreases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Particulate Matter	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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