EPB41L2

Summary

EPB41L2 (erythrocyte membrane protein band 4.1 like 2, HGNC:3379) is a protein-coding gene on chromosome 6q23.1-q23.2, encoding Band 4.1-like protein 2 (O43491). Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase.

Predicted to enable PH domain binding activity; cytoskeletal protein binding activity; and structural molecule activity. Involved in positive regulation of protein localization to cell cortex. Located in several cellular components, including cell cortex; cell junction; and nucleus.

Source: NCBI Gene 2037 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 181 total
• Druggable target: yes
• MANE Select transcript: NM_001431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3379
Approved symbol	EPB41L2
Name	erythrocyte membrane protein band 4.1 like 2
Location	6q23.1-q23.2
Locus type	gene with protein product
Status	Approved
Aliases	4.1-G, 4.1G
Ensembl gene	ENSG00000079819
Ensembl biotype	protein_coding
OMIM	603237
Entrez	2037

Gene structure

Transcript identifiers

Ensembl transcripts: 90 — 82 protein_coding, 4 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000337057, ENST00000368126, ENST00000368128, ENST00000392427, ENST00000445890, ENST00000452150, ENST00000456097, ENST00000524581, ENST00000525193, ENST00000525198, ENST00000525271, ENST00000526333, ENST00000526782, ENST00000526983, ENST00000527017, ENST00000527411, ENST00000527423, ENST00000527659, ENST00000528179, ENST00000528282, ENST00000529208, ENST00000529709, ENST00000530148, ENST00000530481, ENST00000530707, ENST00000530757, ENST00000531356, ENST00000531410, ENST00000532499, ENST00000533912, ENST00000534166, ENST00000628542, ENST00000639623, ENST00000706365, ENST00000904966, ENST00000904967, ENST00000904968, ENST00000904969, ENST00000904970, ENST00000904971, ENST00000904972, ENST00000904973, ENST00000904974, ENST00000904975, ENST00000904976, ENST00000904977, ENST00000904978, ENST00000904979, ENST00000904980, ENST00000904981, ENST00000904982, ENST00000904983, ENST00000904984, ENST00000904985, ENST00000904986, ENST00000904987, ENST00000904988, ENST00000904989, ENST00000904990, ENST00000904991, ENST00000904992, ENST00000904993, ENST00000904994, ENST00000904995, ENST00000904996, ENST00000904997, ENST00000904998, ENST00000904999, ENST00000905000, ENST00000905001, ENST00000922887, ENST00000922888, ENST00000922889, ENST00000922890, ENST00000922891, ENST00000922892, ENST00000922893, ENST00000922894, ENST00000922895, ENST00000922896, ENST00000922897, ENST00000922898, ENST00000922899, ENST00000922900, ENST00000922901, ENST00000969082, ENST00000969083, ENST00000969084, ENST00000969085, ENST00000969086

RefSeq mRNA: 22 — MANE Select: NM_001431 NM_001135554, NM_001135555, NM_001199388, NM_001252660, NM_001350299, NM_001350301, NM_001350302, NM_001350303, NM_001350304, NM_001350305, NM_001350306, NM_001350307, NM_001350308, NM_001350309, NM_001350310, NM_001350311, NM_001350312, NM_001350313, NM_001350314, NM_001350315, NM_001350320, NM_001431

CCDS: CCDS47474, CCDS5141, CCDS56450, CCDS59037, CCDS87439, CCDS87440, CCDS94000

Canonical transcript exons

ENST00000337057 — 20 exons

Exon	Start	End
ENSE00001716285	130839347	130840598
ENSE00002152737	131063155	131063245
ENSE00002451135	130880144	130880206
ENSE00002457106	130894344	130894441
ENSE00002468932	130955105	130955317
ENSE00002485318	130885096	130885268
ENSE00002486533	130899491	130899578
ENSE00002489391	130894967	130895119
ENSE00002500420	130890294	130890466
ENSE00002530032	130878104	130878250
ENSE00002530352	130867459	130867581
ENSE00002729070	130955994	130956499
ENSE00003505079	130863638	130863718
ENSE00003547379	130858131	130858243
ENSE00003570896	130904465	130904540
ENSE00003591123	130926605	130926709
ENSE00003614484	130865536	130865634
ENSE00003639512	130900962	130901180
ENSE00003652577	130908821	130908863
ENSE00003789184	130869563	130870126

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.4906 / max 1736.7729, expressed in 1755 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75549	21.5155	1709
75541	2.9825	520
75548	2.9311	1187
75550	2.2662	1163
75542	1.3250	442
75545	0.1509	4
75534	0.1493	55
75546	0.0891	9
75543	0.0737	38
75544	0.0074	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.61	gold quality
colonic epithelium	UBERON:0000397	99.40	gold quality
sural nerve	UBERON:0015488	99.37	gold quality
tendon of biceps brachii	UBERON:0008188	99.30	gold quality
tendon	UBERON:0000043	99.27	gold quality
corpus callosum	UBERON:0002336	99.10	gold quality
tibial nerve	UBERON:0001323	99.00	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.78	gold quality
inferior olivary complex	UBERON:0002127	98.70	gold quality
medial globus pallidus	UBERON:0002477	98.52	gold quality
trigeminal ganglion	UBERON:0001675	98.42	gold quality
right lung	UBERON:0002167	98.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.28	gold quality
left ovary	UBERON:0002119	98.22	gold quality
inferior vagus X ganglion	UBERON:0005363	98.22	gold quality
spinal cord	UBERON:0002240	98.13	gold quality
globus pallidus	UBERON:0001875	98.07	gold quality
ovary	UBERON:0000992	98.03	gold quality
right uterine tube	UBERON:0001302	97.87	gold quality
right ovary	UBERON:0002118	97.83	gold quality
dorsal root ganglion	UBERON:0000044	97.72	gold quality
parietal pleura	UBERON:0002400	97.65	gold quality
medulla oblongata	UBERON:0001896	97.63	gold quality
olfactory bulb	UBERON:0002264	97.60	gold quality
omental fat pad	UBERON:0010414	97.50	gold quality
peritoneum	UBERON:0002358	97.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.48	gold quality
caudate nucleus	UBERON:0001873	97.40	gold quality
synovial joint	UBERON:0002217	97.36	gold quality
nucleus accumbens	UBERON:0001882	97.33	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	3227.67
E-MTAB-7316	yes	2288.06
E-HCAD-10	yes	46.67
E-HCAD-35	yes	37.72
E-HCAD-25	yes	21.48
E-MTAB-8410	yes	20.21
E-ANND-3	yes	15.50
E-CURD-119	yes	11.89
E-CURD-46	yes	11.35
E-CURD-112	yes	6.52
E-GEOD-130148	yes	6.07
E-MTAB-9543	no	2.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting EPB41L2, 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-3925-3P	100.00	69.95	1237
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3065-3P	99.87	70.25	1407

Literature-anchored findings (GeneRIF, showing 7)

• PTA-1(CD226 antigen) is localized to membrane rafts and binds the carboxyl-terminal domain of isoforms of the actin-binding protein 4.1G and also can bind human discs large providing the structural basis for a regulated molecular adhesive complex (PMID:15138281)
• An alternatively spliced 4.1G product is shown to be associated with increased Fc gamma RI binding in yeast two-hybrid assays, and to be selectively enriched in most immune cells at the transcript level. (PMID:18023480)
• A phosphoserine-dependent tethering role for protein 4.1G in lipid rafts provides insight into the unique phosphoserine-based regulation of FcgammaRI receptor signaling. (PMID:22003208)
• 4.1G protein depresses PTH-related protein receptor-mediated Gs signaling pathway by suppression of adenylyl cyclase-mediated cAMP production. (PMID:23201780)
• Ca(2+)/CaM binding to GHP, and more specifically to pepG, has profound effects on other functional domains of 4.1G (PMID:23354586)
• Data found that direct binding of 4.1G to the N-terminus of AC6 (AC6-N) contributes to the plasma membrane association of AC6-N and the resulting suppression of AC6 cyclase activity. (PMID:31383768)
• Exosomal circEPB41L2 serves as a sponge for miR-21-5p and miR-942-5p to suppress colorectal cancer progression by regulating the PTEN/AKT signalling pathway. (PMID:34022068)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	EPB41L2	ENSDARG00000093374
mus_musculus	Epb41l2	ENSMUSG00000019978
rattus_norvegicus	Epb41l2	ENSRNOG00000012346
drosophila_melanogaster	yrt	FBGN0004049
drosophila_melanogaster	cora	FBGN0010434
drosophila_melanogaster	Frmd5	FBGN0032225
caenorhabditis_elegans	erm-1	WBGENE00001333
caenorhabditis_elegans	frm-1	WBGENE00001488
caenorhabditis_elegans		WBGENE00001489
caenorhabditis_elegans	frm-4	WBGENE00001491

Paralogs (10): MYLIP (ENSG00000007944), EPB41L3 (ENSG00000082397), EPB41L1 (ENSG00000088367), EPB41L4B (ENSG00000095203), EPB41L5 (ENSG00000115109), EPB41L4A (ENSG00000129595), FRMD6 (ENSG00000139926), EPB41 (ENSG00000159023), FRMD5 (ENSG00000171877), FRMD3 (ENSG00000172159)

Protein

Protein identifiers

Band 4.1-like protein 2 — O43491 (reviewed: O43491)

Alternative names: Erythrocyte membrane protein band 4.1-like 2, Generally expressed protein 4.1

All UniProt accessions (18): O43491, A0A2R8Y5B3, A0A994J5B1, E9PHY5, E9PIG0, E9PII3, E9PJP4, E9PK52, E9PMG5, E9PMV8, E9PN54, E9PPC9, E9PQD2, E9PQN0, E9PRG1, H0Y5B0, Q6R5J7, Q6ZSX4

UniProt curated annotations — full annotation on UniProt →

Function. Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase.

Subunit / interactions. Interacts with FCGR1A. Interacts with TRPC4. Interacts (via CTD domain) with FKBP2. Interacts with NUMA1; this interaction is negatively regulated by CDK1 during metaphase and promotes anaphase-specific localization of NUMA1 in symmetrically dividing cells.

Subcellular location. Cytoplasm. Cytoskeleton. Cell cortex. Cell membrane.

Tissue specificity. Widely expressed.

Isoforms (4)

UniProt ID	Names	Canonical?
O43491-1	1	yes
O43491-2	2
O43491-3	3
O43491-4	4

RefSeq proteins (22): NP_001129026, NP_001129027, NP_001186317, NP_001239589, NP_001337228, NP_001337230, NP_001337231, NP_001337232, NP_001337233, NP_001337234, NP_001337235, NP_001337236, NP_001337237, NP_001337238, NP_001337239, NP_001337240, NP_001337241, NP_001337242, NP_001337243, NP_001337244, NP_001337249, NP_001422* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000798	Ez/rad/moesin-like	Family
IPR007477	SAB_dom	Domain
IPR008379	Band_4.1_C	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR014847	FA	Domain
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019747	FERM_CS	Conserved_site
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily

Pfam: PF00373, PF04382, PF05902, PF08736, PF09379, PF09380

UniProt features (47 total): modified residue 23, compositionally biased region 8, region of interest 6, splice variant 4, cross-link 2, initiator methionine 1, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43491-F1	60.14	0.26

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 (25): 2, 7, 39, 58, 87, 89, 170, 208, 386, 402, 499, 550, 562, 575, 598, 614, 623, 627, 647, 715 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins

MSigDB gene sets: 294 (showing top): GCM_MAP4K4, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, KEGG_TIGHT_JUNCTION, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, RODRIGUES_NTN1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN

GO Biological Process (4): cortical actin cytoskeleton organization (GO:0030866), actomyosin structure organization (GO:0031032), cell division (GO:0051301), positive regulation of protein localization to cell cortex (GO:1904778)

GO Molecular Function (6): actin binding (GO:0003779), structural molecule activity (GO:0005198), spectrin binding (GO:0030507), PH domain binding (GO:0042731), protein binding (GO:0005515), cytoskeletal protein binding (GO:0008092)

GO Cellular Component (12): nucleoplasm (GO:0005654), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell cortex (GO:0005938), spectrin (GO:0008091), cell junction (GO:0030054), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), COP9 signalosome (GO:0008180), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
actin cytoskeleton organization	2
cytoskeletal protein binding	2
cytoplasm	2
cell periphery	2
cortical cytoskeleton organization	1
cellular process	1
protein localization to cell cortex	1
positive regulation of protein localization to cell periphery	1
regulation of protein localization to cell cortex	1
molecular_function	1
protein-containing complex binding	1
protein domain specific binding	1
binding	1
protein binding	1
nuclear lumen	1
intracellular membraneless organelle	1
membrane	1
cell-substrate junction	1
cortical actin cytoskeleton	1
protein-containing complex	1
extracellular vesicle	1
intracellular anatomical structure	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EPB41L2	NUMA1	Q14980	834
EPB41L2	CADM4	Q8NFZ8	727
EPB41L2	GRIA1	P42261	664
EPB41L2	GYPC	P04921	646
EPB41L2	MPP1	Q00013	592
EPB41L2	CADM1	Q9BY67	577
EPB41L2	PALS2	Q9NZW5	548
EPB41L2	GRIA4	P48058	543
EPB41L2	CADM3	Q8N126	508
EPB41L2	ANK2	Q01484	471
EPB41L2	FCGR1A	P12314	444
EPB41L2	AKAP7	O43687	429
EPB41L2	IP6K2	Q9UHH9	424
EPB41L2	DDX50	Q9BQ39	420
EPB41L2	EPB41	P11171	415

IntAct

163 interactions, top by confidence:

A	B	Type	Score
LIN7A	CASK	psi-mi:“MI:0914”(association)	0.830
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
DDAH2	EPB41L2	psi-mi:“MI:0914”(association)	0.640
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
FCGR1A	EPB41L2	psi-mi:“MI:0915”(physical association)	0.560
EPB41L2	FCGR1A	psi-mi:“MI:0915”(physical association)	0.560
EPB41L2	FCGR1A	psi-mi:“MI:0403”(colocalization)	0.560
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
EPB41L2	AP3B1	psi-mi:“MI:0914”(association)	0.530
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
DDAH2	OGT	psi-mi:“MI:0914”(association)	0.530
WDR59	EPB41L2	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	TNRC18	psi-mi:“MI:0914”(association)	0.530

BioGRID (373): EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Two-hybrid), EPB41L2 (Reconstituted Complex), EPB41L2 (Proximity Label-MS), EPB41L2 (Proximity Label-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS), EPB41L2 (Affinity Capture-MS)

ESM2 similar proteins: A2ASS6, A8DYP0, E9QMW4, G4SLH0, J7M799, M9MRD1, O15061, O43491, O55103, O70318, O75952, O77788, P07197, P08553, P08855, P11799, P12839, P16053, P27321, P51125, P54938, P57786, P82179, P83741, Q06637, Q13061, Q23551, Q28820, Q4R3X7, Q63425, Q66H38, Q696W0, Q6TS35, Q70IV5, Q7Z589, Q7ZUV7, Q86TC9, Q8BMB0, Q8TC56, Q8WZ42

Diamond homologs: A2A2Y4, A2AD83, A2ALK8, B2RYE5, F1LYQ8, F1P065, F8VPU2, O43491, O57457, O70318, O94887, P11171, P11434, P26045, P28191, P29074, P48193, P52963, Q0P4Q4, Q54K81, Q58CU2, Q5FVG2, Q5R803, Q5RAB8, Q6P5H6, Q6Q7P4, Q6ZUT3, Q7Z6J6, Q8BGS1, Q8BHD4, Q91VS8, Q9H329, Q9H4G0, Q9HCM4, Q9HCS5, Q9JMC8, Q9MYU8, Q9N179, Q9V8R9, Q9WTP0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	48.9×	1e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	43.1×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	43.1×	2e-08
Activation of BH3-only proteins	7	31.9×	1e-07
RHO GTPases activate PKNs	8	23.3×	1e-07
Intrinsic Pathway for Apoptosis	7	18.8×	4e-06
SARS-CoV-1-host interactions	10	16.1×	6e-08
FOXO-mediated transcription	5	15.4×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	13.8×	8e-03
regulation of alternative mRNA splicing, via spliceosome	6	11.0×	8e-03
intracellular protein localization	9	7.1×	6e-03
RNA splicing	9	6.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	149
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

5255 predictions. Top by Δscore:

Variant	Effect	Δscore
6:130863628:A:C	donor_gain	1.0000
6:130863715:CAGT:C	acceptor_gain	1.0000
6:130863717:GT:G	acceptor_gain	1.0000
6:130863719:C:CC	acceptor_gain	1.0000
6:130863727:CA:C	acceptor_gain	1.0000
6:130863728:A:AC	acceptor_gain	1.0000
6:130863728:A:C	acceptor_gain	1.0000
6:130865645:T:C	acceptor_gain	1.0000
6:130865645:T:TC	acceptor_gain	1.0000
6:130878102:ACC:A	donor_gain	1.0000
6:130878103:CCC:C	donor_gain	1.0000
6:130880432:A:C	donor_gain	1.0000
6:130885094:A:AG	donor_loss	1.0000
6:130885095:CCT:C	donor_loss	1.0000
6:130885099:T:A	donor_gain	1.0000
6:130885145:T:TA	donor_gain	1.0000
6:130885146:C:A	donor_gain	1.0000
6:130885264:CGGAG:C	acceptor_gain	1.0000
6:130885265:GGAG:G	acceptor_gain	1.0000
6:130885266:GAG:G	acceptor_gain	1.0000
6:130885266:GAGC:G	acceptor_loss	1.0000
6:130885268:GCTAG:G	acceptor_loss	1.0000
6:130885269:C:CC	acceptor_gain	1.0000
6:130885269:CT:C	acceptor_loss	1.0000
6:130885270:T:G	acceptor_loss	1.0000
6:130890295:T:TA	donor_gain	1.0000
6:130890462:CAAGC:C	acceptor_gain	1.0000
6:130890637:CACAG:C	donor_gain	1.0000
6:130894339:ATTAC:A	donor_loss	1.0000
6:130894341:TACCT:T	donor_loss	1.0000

AlphaMissense

6617 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:130858231:C:G	A975P	1.000
6:130863678:C:G	R957P	1.000
6:130894367:G:C	C488W	1.000
6:130894369:A:G	C488R	1.000
6:130894378:A:G	W485R	1.000
6:130894378:A:T	W485R	1.000
6:130894413:A:G	F473S	1.000
6:130894984:T:C	K458E	1.000
6:130894986:A:T	I457N	1.000
6:130894991:G:C	F455L	1.000
6:130894991:G:T	F455L	1.000
6:130894992:A:G	F455S	1.000
6:130894993:A:G	F455L	1.000
6:130895016:T:A	K447I	1.000
6:130895017:T:C	K447E	1.000
6:130895030:C:A	W442C	1.000
6:130895030:C:G	W442C	1.000
6:130895032:A:G	W442R	1.000
6:130895032:A:T	W442R	1.000
6:130895036:A:C	F440L	1.000
6:130895036:A:T	F440L	1.000
6:130895038:A:G	F440L	1.000
6:130895070:A:G	L429P	1.000
6:130895073:A:G	L428P	1.000
6:130895092:C:G	G422R	1.000
6:130895094:A:G	L421P	1.000
6:130858191:A:T	V988D	0.999
6:130858219:C:G	A979P	0.999
6:130867478:A:T	I904N	0.999
6:130890409:A:C	F515L	0.999

dbSNP variants (sampled 300 via entrez): RS1000018434 (6:130999846 A>C), RS1000023120 (6:131060661 A>T), RS1000026564 (6:131018872 T>G), RS1000028161 (6:130999648 A>C), RS1000051603 (6:130936415 T>C), RS1000066975 (6:131013683 G>A), RS1000068907 (6:130977822 G>A), RS1000099753 (6:130957248 G>A), RS1000115599 (6:130957462 C>T), RS1000121331 (6:130885371 T>A,C), RS1000126994 (6:130929853 A>T), RS1000130745 (6:130847899 T>C,G), RS1000152165 (6:130934191 C>A), RS1000196231 (6:131062024 C>A), RS1000200394 (6:130894429 C>A,G)

Disease associations

OMIM: gene MIM:603237 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST001408_6	Response to statins (LDL cholesterol change)	2.000000e-07
GCST001640_6	Lentiform nucleus volume	5.000000e-06
GCST002596_1	Colorectal cancer (calcium intake interaction)	2.000000e-06
GCST004602_118	Mean corpuscular volume	8.000000e-10
GCST006288_133	Heel bone mineral density	3.000000e-06
GCST006288_461	Heel bone mineral density	1.000000e-10
GCST006288_557	Heel bone mineral density	8.000000e-17
GCST006624_42	Systolic blood pressure	5.000000e-14
GCST006923_13	Loneliness	1.000000e-08
GCST006924_4	Loneliness (MTAG)	1.000000e-09
GCST006979_390	Heel bone mineral density	3.000000e-12
GCST006979_391	Heel bone mineral density	9.000000e-50
GCST007833_7	Urolithiasis	4.000000e-10
GCST008839_529	Height	2.000000e-17
GCST009179_6	Pars triangularis volume	2.000000e-06
GCST009179_7	Pars triangularis volume	4.000000e-07
GCST009254_7	Cerebellum white matter volume	2.000000e-06
GCST009463_12	Loneliness	9.000000e-09
GCST009844_2	Creativity	9.000000e-06
GCST012227_155	Hip circumference adjusted for BMI	2.000000e-09
GCST90000025_73	Appendicular lean mass	2.000000e-13
GCST90002390_450	Mean corpuscular hemoglobin	2.000000e-18
GCST90002396_340	Mean reticulocyte volume	2.000000e-15
GCST90002397_480	Mean spheric corpuscular volume	8.000000e-27
GCST90002400_591	Plateletcrit	2.000000e-12
GCST90020028_190	Hip circumference adjusted for BMI	3.000000e-12
GCST90020028_191	Hip circumference adjusted for BMI	1.000000e-08
GCST90020028_192	Hip circumference adjusted for BMI	1.000000e-11
GCST90020028_193	Hip circumference adjusted for BMI	2.000000e-08
GCST90020028_194	Hip circumference adjusted for BMI	3.000000e-08

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007804	LDL cholesterol change measurement
EFO:0006521	calcium intake measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0007865	loneliness measurement
EFO:0008320	white matter volume measurement
EFO:0010650	creativity measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067036 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	Kd	5.411	nM	CHEMBL3752910
8.27	ED50	5.411	nM	CHEMBL3752910
6.47	Kd	338	nM	CHEMBL5653589
6.47	ED50	338	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148323: Binding affinity to human EPB41L2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0054	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148323: Binding affinity to human EPB41L2 incubated for 45 mins by Kinobead based pull down assay	kd	0.3380	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects expression, decreases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
trichostatin A	affects cotreatment, increases expression	2
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Cisplatin	decreases reaction, affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
Genistein	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	increases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651365	Binding	Binding affinity to human EPB41L2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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