ECT2L

Summary

ECT2L (epithelial cell transforming 2 like, HGNC:21118) is a protein-coding gene on chromosome 6q24.1, encoding Epithelial cell-transforming sequence 2 oncogene-like (Q008S8). May act as a guanine nucleotide exchange factor (GEF).

Predicted to enable guanyl-nucleotide exchange factor activity.

Source: NCBI Gene 345930 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 165 total
• MANE Select transcript: NM_001077706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21118
Approved symbol	ECT2L
Name	epithelial cell transforming 2 like
Location	6q24.1
Locus type	gene with protein product
Status	Approved
Aliases	ARHGEF32, FBXO49, LFDH
Ensembl gene	ENSG00000203734
Ensembl biotype	protein_coding
Entrez	345930

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367682, ENST00000401414, ENST00000495970, ENST00000541398

RefSeq mRNA: 2 — MANE Select: NM_001077706 NM_001077706, NM_001195037

CCDS: CCDS43508

Canonical transcript exons

ENST00000541398 — 22 exons

Exon	Start	End
ENSE00001445363	138849269	138849434
ENSE00001445364	138842979	138843231
ENSE00001445368	138813172	138813340
ENSE00001531504	138902500	138904070
ENSE00001531506	138900948	138901120
ENSE00001531511	138888943	138889031
ENSE00001531513	138886857	138886922
ENSE00001531516	138885674	138885830
ENSE00001531519	138885506	138885579
ENSE00001531522	138882724	138882871
ENSE00001531525	138880957	138881171
ENSE00001531528	138876472	138876558
ENSE00001531550	138846539	138846677
ENSE00001531553	138844412	138844580
ENSE00001547299	138812838	138812977
ENSE00001747099	138814491	138814603
ENSE00003500465	138862627	138862719
ENSE00003520793	138868103	138868206
ENSE00003630928	138864996	138865178
ENSE00003632506	138854026	138854154
ENSE00003704874	138796087	138796192
ENSE00003716460	138838352	138838514

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 88.88.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1382 / max 34.8197, expressed in 48 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70124	0.0608	23
70123	0.0598	25
70125	0.0175	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	88.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.62	gold quality
fallopian tube	UBERON:0003889	70.13	gold quality
heart left ventricle	UBERON:0002084	62.61	gold quality
right lung	UBERON:0002167	61.51	gold quality
calcaneal tendon	UBERON:0003701	60.38	gold quality
pituitary gland	UBERON:0000007	60.05	gold quality
heart	UBERON:0000948	59.76	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.42	silver quality
right atrium auricular region	UBERON:0006631	59.12	gold quality
adenohypophysis	UBERON:0002196	57.22	gold quality
endometrium	UBERON:0001295	56.72	gold quality
ventricular zone	UBERON:0003053	56.49	gold quality
lung	UBERON:0002048	56.25	gold quality
cerebellar hemisphere	UBERON:0002245	54.93	gold quality
cerebellar cortex	UBERON:0002129	54.89	gold quality
cerebellum	UBERON:0002037	54.72	gold quality
bone marrow cell	CL:0002092	54.68	gold quality
Ammon’s horn	UBERON:0001954	54.44	gold quality
mucosa of transverse colon	UBERON:0004991	53.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	53.72	gold quality
corpus callosum	UBERON:0002336	53.71	gold quality
mucosa of stomach	UBERON:0001199	53.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	53.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	52.72	gold quality
hypothalamus	UBERON:0001898	52.59	gold quality
anterior cingulate cortex	UBERON:0009835	52.18	gold quality
granulocyte	CL:0000094	51.97	gold quality
caudate nucleus	UBERON:0001873	51.82	gold quality
upper lobe of left lung	UBERON:0008952	51.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting ECT2L, 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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
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-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4422	99.72	72.07	2908

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ect2l	ENSDARG00000091471
mus_musculus	Ect2l	ENSMUSG00000071392
rattus_norvegicus	Ect2l	ENSRNOG00000055142
caenorhabditis_elegans		WBGENE00001366
caenorhabditis_elegans		WBGENE00001490

Paralogs (10): FARP2 (ENSG00000006607), FGD1 (ENSG00000102302), FGD3 (ENSG00000127084), ARHGEF39 (ENSG00000137135), FGD4 (ENSG00000139132), FGD2 (ENSG00000146192), FARP1 (ENSG00000152767), FGD5 (ENSG00000154783), FRMD7 (ENSG00000165694), FGD6 (ENSG00000180263)

Protein

Protein identifiers

Epithelial cell-transforming sequence 2 oncogene-like — Q008S8 (reviewed: Q008S8)

Alternative names: Lung-specific F-box and DH domain-containing protein, Putative guanine nucleotide exchange factor LFDH

All UniProt accessions (2): B7ZBI6, Q008S8

UniProt curated annotations — full annotation on UniProt →

Function. May act as a guanine nucleotide exchange factor (GEF).

RefSeq proteins (2): NP_001071174, NP_001181966 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001810	F-box_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR025592	DUF4347	Domain
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036047	F-box-like_dom_sf	Homologous_superfamily
IPR052805	GEF_Ubiquitin-Prot_Reg	Family

Pfam: PF00621, PF12937, PF14252

UniProt features (10 total): sequence conflict 4, sequence variant 3, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q008S8-F1	74.75	0.22

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, PAX3_TARGET_GENES, ZNF22_TARGET_GENES, MIR335_3P, MIR3658, MIR4262, MIR561_3P, MIR4766_5P, MIR7154_5P, MIR595, MIR3614_3P, MIR1243

GO Biological Process (0):

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1

Protein interactions and networks

STRING

716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ECT2L	FBXO48	Q5FWF7	590
ECT2L	FBXO47	Q5MNV8	587
ECT2L	CCDC28A	Q8IWP9	530
ECT2L	NPIPA7	E9PJI5	506
ECT2L	Q8WV35	Q8WV35	425
ECT2L	LMO7	Q8WWI1	418
ECT2L	FGD5	Q6ZNL6	416
ECT2L	FBXL15	Q9H469	410
ECT2L	ARHGEF19	Q8IW93	402
ECT2L	FBXL22	Q6P050	402
ECT2L	FBXL13	Q8NEE6	398
ECT2L	FBXO25	Q8TCJ0	385
ECT2L	FBXO33	Q7Z6M2	382
ECT2L	FBXL7	Q9UJT9	376
ECT2L	FBXL14	Q8N1E6	375

IntAct

13 interactions, top by confidence:

A	B	Type	Score
GSTM3	ECT2L	psi-mi:“MI:0914”(association)	0.530
GSTM3	GSTM2	psi-mi:“MI:0914”(association)	0.530
ECT2L	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
ECT2L	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
ECT2L	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ECT2L	NEFL	psi-mi:“MI:0914”(association)	0.350
DGKZ	RRP8	psi-mi:“MI:0914”(association)	0.350
ECT2L	TOMM40	psi-mi:“MI:0914”(association)	0.350
ZNF436	PNLIPRP2	psi-mi:“MI:0914”(association)	0.350
KCTD19	ECT2L	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): ECT2L (Affinity Capture-MS), ECT2L (Affinity Capture-MS), ECT2L (Proximity Label-MS), ECT2L (Proximity Label-MS), ECT2L (Proximity Label-MS), ECT2L (Affinity Capture-MS), ECT2L (Affinity Capture-MS), CHP1 (Affinity Capture-MS), CTNNA1 (Affinity Capture-MS), INA (Affinity Capture-MS), MLLT11 (Affinity Capture-MS), MRPL10 (Affinity Capture-MS), NEFL (Affinity Capture-MS), PKP2 (Affinity Capture-MS), PSMA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JEB6, A0JM56, B0DOB4, B0FXQ5, B1ANS9, B4F7L9, B4GQJ7, B5DHW4, B7FF06, B7FF07, B7FF08, B7FF09, B7FF12, C5IAW9, F1LW30, F1P4W9, O08747, O95185, P0DM40, Q008S8, Q18264, Q32NR9, Q3V0B4, Q402B2, Q4G0P3, Q5R4M2, Q5T0N1, Q5XI14, Q6AXU1, Q6DCF6, Q6NRS1, Q6P2C0, Q6P5D8, Q6UXZ4, Q6ZTR5, Q6ZU64, Q761X5, Q7T2Z5, Q80W93, Q86YR7

Diamond homologs: A1C7E4, A1CBP8, A1CUD6, A1DDL6, A1DHW6, A1DP19, A2QCU8, A2R3Z3, A3LNI7, A4RJV3, A5D7H2, A7EKM8, B0XM00, B0XTS1, B2VWG7, B6GZA1, B6Q4Z5, B6QC06, B6QC56, B8M0Q1, B8M7Q5, B8NGT5, C0S902, C1GB49, C5FP68, C5GVJ9, C5JD40, D1ZEM6, D4AM37, D4D8P3, L7N1X6, O43815, O55106, P0DL28, P39014, P58404, P58405, P70483, P87053, Q00659

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4350 predictions. Top by Δscore:

Variant	Effect	Δscore
6:138838496:G:GT	donor_gain	1.0000
6:138843227:TAAGA:T	donor_gain	1.0000
6:138843228:AAGA:A	donor_gain	1.0000
6:138843230:GA:G	donor_gain	1.0000
6:138843232:G:GG	donor_gain	1.0000
6:138844410:A:AG	acceptor_gain	1.0000
6:138844411:G:GG	acceptor_gain	1.0000
6:138868102:GGGCA:G	acceptor_gain	1.0000
6:138868207:G:GG	donor_gain	1.0000
6:138812929:GCAAA:G	donor_gain	0.9900
6:138813336:GACAG:G	donor_gain	0.9900
6:138814486:TATAG:T	acceptor_gain	0.9900
6:138814487:ATAGC:A	acceptor_gain	0.9900
6:138814488:TAG:T	acceptor_gain	0.9900
6:138838496:G:T	donor_gain	0.9900
6:138843229:AGAG:A	donor_loss	0.9900
6:138843230:GAGTA:G	donor_loss	0.9900
6:138843231:AGT:A	donor_loss	0.9900
6:138843232:G:A	donor_loss	0.9900
6:138843233:T:A	donor_loss	0.9900
6:138843234:AAGTA:A	donor_loss	0.9900
6:138844410:AGAG:A	acceptor_gain	0.9900
6:138844411:GA:G	acceptor_gain	0.9900
6:138844411:GAGG:G	acceptor_gain	0.9900
6:138844411:GAGGA:G	acceptor_gain	0.9900
6:138844578:GCG:G	donor_gain	0.9900
6:138844581:G:GG	donor_gain	0.9900
6:138849264:TCCAG:T	acceptor_loss	0.9900
6:138849265:CCAGA:C	acceptor_loss	0.9900
6:138849267:AGA:A	acceptor_loss	0.9900

AlphaMissense

5958 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:138843057:T:A	W141R	0.993
6:138843057:T:C	W141R	0.993
6:138838494:T:A	W108R	0.991
6:138838494:T:C	W108R	0.991
6:138854076:T:A	W374R	0.991
6:138854076:T:C	W374R	0.991
6:138843015:T:A	W127R	0.990
6:138843015:T:C	W127R	0.990
6:138814536:T:A	W38R	0.989
6:138814536:T:C	W38R	0.989
6:138842988:T:A	W118R	0.986
6:138842988:T:C	W118R	0.986
6:138902580:T:A	W890R	0.983
6:138902580:T:C	W890R	0.983
6:138843059:G:C	W141C	0.982
6:138843059:G:T	W141C	0.982
6:138865073:T:A	W457R	0.982
6:138865073:T:C	W457R	0.982
6:138843002:C:G	C122W	0.980
6:138885685:T:C	L705P	0.978
6:138813305:T:A	W11R	0.977
6:138813305:T:C	W11R	0.977
6:138843000:T:C	C122R	0.976
6:138814505:A:C	R27S	0.974
6:138814505:A:T	R27S	0.974
6:138814552:G:C	R43P	0.974
6:138862654:T:C	L409P	0.973
6:138900998:T:C	L822P	0.973
6:138842990:G:C	W118C	0.971
6:138842990:G:T	W118C	0.971

dbSNP variants (sampled 300 via entrez): RS1000012133 (6:138843140 T>C), RS1000144186 (6:138869437 G>A), RS1000156601 (6:138835124 A>T), RS1000252896 (6:138826800 GGT>G), RS1000271444 (6:138887083 C>T), RS1000327183 (6:138820727 C>CT), RS1000351614 (6:138802741 G>T), RS1000373392 (6:138831536 T>A), RS1000379020 (6:138872505 C>T), RS1000406023 (6:138869644 C>T), RS1000437181 (6:138878719 T>A,C), RS1000489521 (6:138831136 C>T), RS1000491756 (6:138794340 G>A,C), RS1000494034 (6:138884405 A>T), RS1000517695 (6:138854298 G>C)

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

1 associations (top):

Study	Trait	p-value
GCST003208_5	Colorectal or endometrial cancer	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004230	endometrial neoplasm

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11155012	Efficacy	3	anthracyclines and related substances	Breast Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11155012	ECT2L	3	1.75	1	anthracyclines and related substances

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
aflatoxin B2	decreases methylation	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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