EFHD2

Summary

EFHD2 (EF-hand domain family member D2, HGNC:28670) is a protein-coding gene on chromosome 1p36.21, encoding EF-hand domain-containing protein D2 (Q96C19). May regulate B-cell receptor (BCR)-induced immature and primary B-cell apoptosis.

Enables cadherin binding activity. Predicted to be located in membrane raft.

Source: NCBI Gene 79180 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 32 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28670
Approved symbol	EFHD2
Name	EF-hand domain family member D2
Location	1p36.21
Locus type	gene with protein product
Status	Approved
Aliases	MGC4342
Ensembl gene	ENSG00000142634
Ensembl biotype	protein_coding
OMIM	616450
Entrez	79180

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000375980, ENST00000445566, ENST00000906256, ENST00000906257, ENST00000968587, ENST00000968588

RefSeq mRNA: 1 — MANE Select: NM_024329 NM_024329

CCDS: CCDS155

Canonical transcript exons

ENST00000375980 — 4 exons

Exon	Start	End
ENSE00001012099	15427150	15427284
ENSE00001765643	15425871	15426018
ENSE00001765949	15428593	15430339
ENSE00001921931	15409888	15410279

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.2208 / max 1526.4933, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
846	57.2208	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.41	gold quality
leukocyte	CL:0000738	98.56	gold quality
monocyte	CL:0000576	98.54	gold quality
mononuclear cell	CL:0000842	98.51	gold quality
blood	UBERON:0000178	97.77	gold quality
mucosa of transverse colon	UBERON:0004991	97.28	gold quality
pons	UBERON:0000988	97.19	gold quality
left testis	UBERON:0004533	96.99	gold quality
right testis	UBERON:0004534	96.98	gold quality
spleen	UBERON:0002106	96.96	gold quality
lower esophagus mucosa	UBERON:0035834	96.40	gold quality
anterior cingulate cortex	UBERON:0009835	96.26	gold quality
cingulate cortex	UBERON:0003027	96.24	gold quality
palpebral conjunctiva	UBERON:0001812	96.01	gold quality
male germ cell	CL:0000015	95.82	gold quality
sperm	CL:0000019	95.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.65	gold quality
transverse colon	UBERON:0001157	95.60	gold quality
body of stomach	UBERON:0001161	95.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.50	gold quality
testis	UBERON:0000473	95.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.37	gold quality
right frontal lobe	UBERON:0002810	95.35	gold quality
nasal cavity epithelium	UBERON:0005384	95.15	gold quality
small intestine	UBERON:0002108	94.84	gold quality
vermiform appendix	UBERON:0001154	94.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.64	gold quality
right adrenal gland cortex	UBERON:0035827	94.40	gold quality
body of pancreas	UBERON:0001150	94.36	gold quality
left adrenal gland cortex	UBERON:0035825	94.32	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	95.80
E-MTAB-9467	yes	57.85
E-CURD-122	yes	50.09
E-ANND-3	yes	20.36
E-MTAB-9067	yes	10.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JUN, NFKB

miRNA regulators (miRDB)

105 targeting EFHD2, 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-8485	100.00	77.57	4731
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3185	99.99	68.12	1959
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-7110-5P	99.80	67.84	1712

Literature-anchored findings (GeneRIF, showing 20)

• Its predominant presence in CD8 lymphocytes suggests that swiprosin-1 may be involved in functions that are important for cytotoxic lymphocytes. (PMID:15274114)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• These results suggest that swiprosin-1 is a PKC-beta I/eta-inducible gene and it modulates mast cell activation through NF-kappaB-dependent pathway. (PMID:19693767)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• the human Shu complex (hSWS1.SWSAP1) has an evolutionarily conserved function in homologous recombination (PMID:21965664)
• EFhd2 may play an important role in the pathobiology of tau-mediated neurodegeneration. (PMID:23331044)
• Swiprosin-1 is involved in regulating the accessibility of F-actin to cofilin through the clustering of F-actin and the activity of Swiprosin-1 is highly dependent on its phosphorylation status at Ser183 (PMID:23959172)
• Swiprosin-1 localizes to microvilli-like membrane protrusions and lamellipodia and exhibits actin-binding activity. (PMID:23977092)
• The results imply that EFhd2’s physiological and/or pathological function could be regulated by its phosphorylation state. (PMID:24917152)
• EFhd2 is involved in the control of synapse development and maintenance and is linked to dementia. (PMID:25383639)
• Data demonstrate that EFhd2 shows unique structural and biological features as an EF-hand containing F-actin bundling protein. For F-actin bundling activity, structural stabilization of the EF-hand domains was found to occur in the presence of Ca2+. The core region of EFhd2 maintains its structure in the absence of Ca2+ ; however, changes in local conformational flexibility reduce F-actin bundling activity of EFhd2. (PMID:27974828)
• Phosphorylation at Ser183 of EFhd2 causes changes in the local conformational dynamics and the surface charge distribution of the actin-binding site, resulting in a re-coordination of the actin-binding sites in the dimer structure. (PMID:28011271)
• EFHD2 was identified as expressed in highly metastatic tumor cells. EFHD2 increased the formation of protrusive invadopodia structures and cell migration and invasion abilities and promoted the epithelial-to-mesenchymal transition (EMT) character of lung adenocarcinoma cells. We demonstrated that the mechanism of EFHD2 in enhancing EMT occurs partly through inhibition of caveolin-1 (CAV1) for cancer progression. (PMID:29097801)
• MOES, ANXA5 and EFHD2 were confirmed by selected reaction monitoring to be correlated to monocytic differentiation, and could be biomarkers for disease stratification in AML (PMID:29175091)
• EFHD2 is an important regulator of T cell cytotoxicity and further studies should evaluate its role in T cell-mediated inflammation (PMID:30275048)
• first time we have identified the -100/+41 to -70/+41 bp core promoter regions of Swiprosin-1 gene, and showed ADR1 and Sp1 are important transcription factors that directly bind to and transactivate the Swiprosin-1 promoter region. (PMID:30405162)
• our study uncovers a protein complex, which consists of SWS1, SWSAP1, SPIDR and PDS5B, involved in DNA repair and provides insight into Shu complex function and composition (PMID:31665741)
• EFHD2 contributes to non-small cell lung cancer cisplatin resistance by the activation of NOX4-ROS-ABCC1 axis. (PMID:32446175)
• Association between EFHD2 gene polymorphisms and schizophrenia among the Han population in northern China. (PMID:32567430)
• Role of Swiprosin-1/EFHD2 as a biomarker in the development of chronic diseases. (PMID:35276221)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	efhd2	ENSDARG00000055759
mus_musculus	Efhd2	ENSMUSG00000040659
rattus_norvegicus	Efhd2	ENSRNOG00000013783
drosophila_melanogaster	Swip-1	FBGN0032731
drosophila_melanogaster	CG14861	FBGN0038280
caenorhabditis_elegans		WBGENE00012980

Paralogs (1): EFHD1 (ENSG00000115468)

Protein

Protein identifiers

EF-hand domain-containing protein D2 — Q96C19 (reviewed: Q96C19)

Alternative names: Swiprosin-1

All UniProt accessions (3): Q96C19, A0A024QZ77, H0Y4Y4

UniProt curated annotations — full annotation on UniProt →

Function. May regulate B-cell receptor (BCR)-induced immature and primary B-cell apoptosis. Plays a role as negative regulator of the canonical NF-kappa-B-activating branch. Controls spontaneous apoptosis through the regulation of BCL2L1 abundance.

Subunit / interactions. Interacts with CASP9; with inactive form.

Subcellular location. Membrane raft.

Tissue specificity. Found in lymphocytes; preferentially expressed in CD8+ cells.

RefSeq proteins (1): NP_077305* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR040365	EFHD1/2	Family
IPR049025	AIF-1_EF_pair	Domain

Pfam: PF21008

UniProt features (28 total): binding site 8, modified residue 6, helix 6, strand 3, domain 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5I2L	X-RAY DIFFRACTION	1.85
5H0P	X-RAY DIFFRACTION	1.86
5I2Q	X-RAY DIFFRACTION	1.94
5I2O	X-RAY DIFFRACTION	1.95
7YGY	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96C19-F1	75.28	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.

Ligand- & substrate-binding residues (8): 145; 147; 152; 105; 109; 116; 141; 143

Post-translational modifications (6): 2, 11, 74, 76, 83, 233

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9013405	RHOD GTPase cycle

MSigDB gene sets: 246 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, SHEPARD_BMYB_MORPHOLINO_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOLDRATH_ANTIGEN_RESPONSE, WEI_MYCN_TARGETS_WITH_E_BOX, VALK_AML_CLUSTER_5, GNF2_CD97, COATES_MACROPHAGE_M1_VS_M2_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, RFX1_02, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS

GO Biological Process (0):

GO Molecular Function (3): calcium ion binding (GO:0005509), cadherin binding (GO:0045296), metal ion binding (GO:0046872)

GO Cellular Component (2): membrane raft (GO:0045121), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	1
cell adhesion molecule binding	1
cation binding	1
membrane microdomain	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EFHD2	UACA	Q9BZF9	561
EFHD2	IMMT	Q16891	499
EFHD2	INVS	Q9Y283	488
EFHD2	PAWR	Q96IZ0	482
EFHD2	FLII	Q13045	474
EFHD2	U2AF2	P26368	464
EFHD2	TRIM21	P19474	435
EFHD2	WSB1	Q9Y6I7	433
EFHD2	DOP1A	Q5JWR5	430
EFHD2	LGALS3	P17931	426
EFHD2	RDX	P35241	422
EFHD2	MSN	P26038	420
EFHD2	PUS7	Q96PZ0	403
EFHD2	RIT2	Q99578	393
EFHD2	ADRB2	P07550	375

IntAct

66 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530
OR5F1	UBA6	psi-mi:“MI:0914”(association)	0.530
TAS2R41	YKT6	psi-mi:“MI:0914”(association)	0.530
OR2K2	NME2P1	psi-mi:“MI:0914”(association)	0.530
RDH12	NME2P1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
EFHD2	MYH10	psi-mi:“MI:0915”(physical association)	0.400
TYMS	EFHD2	psi-mi:“MI:0915”(physical association)	0.400
RAD51D	EFHD2	psi-mi:“MI:0915”(physical association)	0.400
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Actb		psi-mi:“MI:0914”(association)	0.350
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Calml3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Myh9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
EFHD2	Vps26b	psi-mi:“MI:0914”(association)	0.350
PRKD1		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (163): ACTR2 (Co-fractionation), ARPC2 (Co-fractionation), ARPC3 (Co-fractionation), ARPC4-TTLL3 (Co-fractionation), ARPC4 (Co-fractionation), EFHD2 (Co-fractionation), TMOD1 (Co-fractionation), VARS (Co-fractionation), EFHD2 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6A2H6, A2VEI2, A4IG32, A4IHK8, A5D7A0, D2HZB0, D4A1F2, E9Q4Z2, F1MF74, O00763, O08874, O14795, O94851, P23092, Q05AA6, Q08BI9, Q13474, Q17QM6, Q3TWN3, Q4FZY0, Q4KUS2, Q4V8B2, Q5E9V1, Q5R9G1, Q5RDI4, Q5U2P1, Q5ZJT0, Q62768, Q62769, Q69ZT9, Q6DFA1, Q86XE3, Q8BHD4, Q8BML1, Q8IWE4, Q8K0V2, Q8WN03, Q96C19, Q9BQI0, Q9BUP0

Diamond homologs: A5D7A0, O70200, O81092, P04112, P04113, P05944, P29289, P54680, P55008, P55009, P81076, Q09011, Q11083, Q17QM6, Q32LE3, Q4FZY0, Q54QX0, Q5RDI4, Q5TM25, Q8VWY7, Q96C19, Q9AWK2, Q9BDK2, Q9BQI0, Q9BUP0, Q9D4J1, Q9D8Y0, Q9EQX4, Q9SRP7, Q9VJ26, O60041, O96102, P06787, P14533, P25071, P80322, Q09665, Q12798, Q9XZP2, A4IF97

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
RHO GTPase Effectors	6	7.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
152293	GRCh38/hg38 1p36.22-36.21(chr1:9428538-15815791)x1	Pathogenic

SpliceAI

432 predictions. Top by Δscore:

Variant	Effect	Δscore
1:15410276:AGCA:A	donor_gain	1.0000
1:15410277:GCA:G	donor_gain	1.0000
1:15410277:GCAG:G	donor_gain	1.0000
1:15410278:CA:C	donor_gain	1.0000
1:15410280:G:GG	donor_gain	1.0000
1:15425863:A:AG	acceptor_gain	1.0000
1:15425863:ATCT:A	acceptor_gain	1.0000
1:15425864:T:G	acceptor_gain	1.0000
1:15425866:TGCA:T	acceptor_loss	1.0000
1:15425867:GCAG:G	acceptor_loss	1.0000
1:15425868:CA:C	acceptor_loss	1.0000
1:15425869:A:AG	acceptor_gain	1.0000
1:15425869:A:AT	acceptor_loss	1.0000
1:15425869:AG:A	acceptor_gain	1.0000
1:15425870:G:GT	acceptor_gain	1.0000
1:15425870:GG:G	acceptor_gain	1.0000
1:15425870:GGT:G	acceptor_gain	1.0000
1:15425870:GGTA:G	acceptor_gain	1.0000
1:15425870:GGTAT:G	acceptor_gain	1.0000
1:15425977:G:GT	donor_gain	1.0000
1:15426004:C:G	donor_gain	1.0000
1:15426014:GGGAG:G	donor_gain	1.0000
1:15426015:GGAG:G	donor_gain	1.0000
1:15426015:GGAGG:G	donor_gain	1.0000
1:15426016:G:T	donor_gain	1.0000
1:15426016:GAG:G	donor_gain	1.0000
1:15426016:GAGG:G	donor_gain	1.0000
1:15426017:AG:A	donor_gain	1.0000
1:15426018:GG:G	donor_gain	1.0000
1:15426019:G:GA	donor_loss	1.0000

AlphaMissense

1599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:15425912:T:C	L117P	0.999
1:15425960:T:C	L133P	0.999
1:15427150:T:C	F153L	0.999
1:15427152:C:A	F153L	0.999
1:15427152:C:G	F153L	0.999
1:15427273:T:C	F194L	0.999
1:15427275:T:A	F194L	0.999
1:15427275:T:G	F194L	0.999
1:15410227:T:C	F86L	0.998
1:15410229:C:A	F86L	0.998
1:15410229:C:G	F86L	0.998
1:15410272:T:C	F101L	0.998
1:15410273:T:C	F101S	0.998
1:15410274:C:A	F101L	0.998
1:15410274:C:G	F101L	0.998
1:15425925:G:A	M121I	0.998
1:15425925:G:C	M121I	0.998
1:15425925:G:T	M121I	0.998
1:15425950:C:G	H130D	0.998
1:15425952:C:A	H130Q	0.998
1:15425952:C:G	H130Q	0.998
1:15427154:T:C	L154P	0.998
1:15427279:G:C	A196P	0.998
1:15410228:T:C	F86S	0.997
1:15410237:T:C	F89S	0.997
1:15425897:T:A	I112N	0.997
1:15425916:A:C	K118N	0.997
1:15425916:A:T	K118N	0.997
1:15426005:T:A	L148Q	0.997
1:15427151:T:C	F153S	0.997

dbSNP variants (sampled 300 via entrez): RS1000093085 (1:15423266 G>A), RS1000244601 (1:15421762 T>G), RS1000271375 (1:15411060 C>T), RS1000622675 (1:15422233 C>T), RS1000637696 (1:15427367 C>A,T), RS1000708242 (1:15421884 T>C), RS1000898446 (1:15417501 C>G,T), RS1000969120 (1:15418509 G>A,C,T), RS1001006450 (1:15412170 G>A), RS1001301297 (1:15411615 G>A,T), RS1001695872 (1:15421832 G>A), RS1001836443 (1:15421794 G>C), RS1001946371 (1:15416907 T>G), RS1002040556 (1:15426659 G>A), RS1002315567 (1:15416690 C>T)

Disease associations

OMIM: gene MIM:616450 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004860_120	Alcoholic chronic pancreatitis	6.000000e-06
GCST004860_132	Alcoholic chronic pancreatitis	2.000000e-10
GCST004860_133	Alcoholic chronic pancreatitis	8.000000e-09
GCST004860_18	Alcoholic chronic pancreatitis	1.000000e-07
GCST004860_43	Alcoholic chronic pancreatitis	3.000000e-22
GCST004860_47	Alcoholic chronic pancreatitis	3.000000e-06
GCST004860_67	Alcoholic chronic pancreatitis	8.000000e-10
GCST004860_68	Alcoholic chronic pancreatitis	2.000000e-07
GCST004860_69	Alcoholic chronic pancreatitis	6.000000e-07
GCST004860_81	Alcoholic chronic pancreatitis	1.000000e-16
GCST004860_94	Alcoholic chronic pancreatitis	1.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724911 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.81	Kd	15.51	nM	CHEMBL5653589
7.68	ED50	20.8	nM	CHEMBL5653589
5.34	IC50	4550	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148290: Binding affinity to human EFHD2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0155	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178644: Inhibition of EFHD2 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	4.5500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	3
Valproic Acid	affects expression, affects cotreatment, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	affects binding, increases reaction, decreases phosphorylation	2
Nickel	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
polyhexamethyleneguanidine	affects expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	decreases phosphorylation	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	increases abundance, affects expression	1
Caffeine	decreases phosphorylation	1
Carcinogens	decreases expression	1
Copper	decreases expression, affects binding	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651332	Binding	Binding affinity to human EFHD2 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.