ELMO1

Summary

ELMO1 (engulfment and cell motility 1, HGNC:16286) is a protein-coding gene on chromosome 7p14.2-p14.1, encoding Engulfment and cell motility protein 1 (Q92556). Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.

This gene encodes a member of the engulfment and cell motility protein family. These proteins interact with dedicator of cytokinesis proteins to promote phagocytosis and cell migration. Increased expression of this gene and dedicator of cytokinesis 1 may promote glioma cell invasion, and single nucleotide polymorphisms in this gene may be associated with diabetic nephropathy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9844 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC)
• GWAS associations: 53
• Clinical variants (ClinVar): 83 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16286
Approved symbol	ELMO1
Name	engulfment and cell motility 1
Location	7p14.2-p14.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0281, CED12, ELMO-1, CED-12
Ensembl gene	ENSG00000155849
Ensembl biotype	protein_coding
OMIM	606420
Entrez	9844

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 19 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000310758, ENST00000396040, ENST00000396045, ENST00000420636, ENST00000424212, ENST00000433246, ENST00000442504, ENST00000445322, ENST00000448602, ENST00000453399, ENST00000455119, ENST00000455879, ENST00000463390, ENST00000464262, ENST00000472359, ENST00000479447, ENST00000487336, ENST00000487843, ENST00000497024, ENST00000898964, ENST00000898965, ENST00000898966, ENST00000898967, ENST00000898968, ENST00000898969, ENST00000898970, ENST00000963263

RefSeq mRNA: 5 — MANE Select: NM_014800 NM_001039459, NM_001206480, NM_001206482, NM_014800, NM_130442

CCDS: CCDS5449, CCDS5450

Canonical transcript exons

ENST00000310758 — 22 exons

Exon	Start	End
ENSE00001085399	36887560	36887672
ENSE00001595607	37259181	37259350
ENSE00001658214	37224879	37225030
ENSE00001717611	37233095	37233194
ENSE00001863123	37448675	37448864
ENSE00003465766	37211386	37211517
ENSE00003474705	36861659	36861736
ENSE00003475119	37133130	37133234
ENSE00003525187	36870393	36870475
ENSE00003537637	37216645	37216695
ENSE00003572532	37013299	37013435
ENSE00003574587	36878010	36878117
ENSE00003603245	37213335	37213457
ENSE00003644365	37342613	37342763
ENSE00003651973	37096619	37096727
ENSE00003655801	36894854	36895017
ENSE00003661291	37314850	37314922
ENSE00003675257	37315920	37315960
ENSE00003693336	37222615	37222693
ENSE00003785658	37271832	37271882
ENSE00003786520	37244356	37244391
ENSE00003913573	36852906	36855751

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.5182 / max 1177.9643, expressed in 1021 samples.

FANTOM5 promoters (28 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83631	16.2113	933
83621	6.0218	442
83608	5.8270	182
83638	1.6059	227
83626	1.4975	184
83633	0.9932	369
83634	0.6505	297
83627	0.5532	167
83607	0.5493	105
83630	0.5296	256

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	98.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.65	gold quality
corpus callosum	UBERON:0002336	97.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.46	gold quality
sural nerve	UBERON:0015488	97.44	gold quality
right frontal lobe	UBERON:0002810	97.39	gold quality
islet of Langerhans	UBERON:0000006	97.30	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.18	gold quality
postcentral gyrus	UBERON:0002581	96.95	gold quality
frontal cortex	UBERON:0001870	96.93	gold quality
frontal lobe	UBERON:0016525	96.93	gold quality
ganglionic eminence	UBERON:0004023	96.92	gold quality
cingulate cortex	UBERON:0003027	96.89	gold quality
anterior cingulate cortex	UBERON:0009835	96.85	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.71	gold quality
calcaneal tendon	UBERON:0003701	96.69	gold quality
spinal cord	UBERON:0002240	96.68	gold quality
parietal lobe	UBERON:0001872	96.56	gold quality
pons	UBERON:0000988	96.47	gold quality
neocortex	UBERON:0001950	96.41	gold quality
cerebellar hemisphere	UBERON:0002245	96.35	gold quality
nucleus accumbens	UBERON:0001882	96.33	gold quality
frontal pole	UBERON:0002795	96.33	gold quality
cerebellar cortex	UBERON:0002129	96.31	gold quality
tibial nerve	UBERON:0001323	96.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.12	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.05	gold quality
cerebellum	UBERON:0002037	96.00	gold quality
amygdala	UBERON:0001876	95.95	gold quality
putamen	UBERON:0001874	95.90	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	2728.78
E-GEOD-131882	yes	2531.94
E-HCAD-35	yes	108.09
E-HCAD-25	yes	58.49
E-GEOD-81608	yes	19.37
E-MTAB-5061	yes	17.50
E-GEOD-93593	yes	14.70
E-ENAD-27	yes	11.86
E-GEOD-83139	yes	11.01
E-ANND-2	no	1647.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2, TAL1

miRNA regulators (miRDB)

157 targeting ELMO1, 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-6740-5P	100.00	65.64	932
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-185-3P	99.95	67.01	1743

Literature-anchored findings (GeneRIF, showing 40)

• Dock180 ELMO complex functions as an unconventional two-part exchange factor for Rac. (PMID:12134158)
• the association of DOCK2 with ELMO1 is critical for DOCK2-mediated Rac activation, thereby suggesting that their association might be a therapeutic target for immunologic disorders caused by lymphocyte infiltration (PMID:12829596)
• Rac activation by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 plays a role in cell migration (PMID:14638695)
• Nef binds the DOCK2-ELMO1 complex to activate rac and inhibit lymphocyte chemotaxis (PMID:14737186)
• while N-terminal SH3 of CrkII promotes assembly between CrkII and DOCK180, the C-terminal SH3 of CrkII regulates the stability and turnover of the DOCK180/ELMO complex (PMID:15700267)
• ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. (PMID:15723800)
• These results indicate that ELMO1 is a novel candidate gene that both confers susceptibility to diabetic nephropathy and plays an important role in the development and progression of this disease. (PMID:15793258)
• Src family kinase mediated tyrosine phosphorylation of ELMO1 might represent an important regulatory mechanism that controls signaling through the ELMO1/Crk/Dock180 pathway. (PMID:15952790)
• ARNO and ARF6 coordinate with the Dock180/Elmo complex to promote Rac activation at the leading edge of migrating cells. (PMID:16213822)
• Using pulldown assays, we identified engulfment and cell motility (ELMO) protein as the IpgB1 binding partner. IpgB1 colocalized with ELMO and Dock180 in membrane ruffles induced by Shigella. (PMID:17173036)
• Overexpression of ELMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor is associated with glioma cell invasion (PMID:17671188)
• The DOCK180-ELMO1 interaction is mapped to the N-terminal 200 amino acids of DOCK180, and to the C-terminal 200 amino acids of ELMO1, comprising the ELMO1 PH domain. (PMID:18768751)
• Variants in intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in African Americans. (PMID:19183347)
• Report of genetic associations in ELMO1 with diabetic nephropathy, further establishing its role in the susceptibility of this disease. (PMID:19651817)
• The protein-protein interaction between ELMO1 and COX-2 increased the cyclooxygenase activity of COX-2 and, correspondingly, fibronectin expression.(ELMO1 protein, human) (PMID:20732417)
• We sequenced 17.4 kb of ELMO1 and identified 19 variants. (PMID:20826100)
• findings demonstrate an in vivo role for ELMO1-dependent clearance in the testes, with implications for spermatogenesis (PMID:20958313)
• The C-terminal Pro-rich tail of ELMO1 winds around the Src-homology 3 domain of DOCK2 to form an intermolecular 5-helix bundle. The entire regions of both DOCK2 a& ELMO1 assemble to create a rigid structure required for the DOCK2 & ELMO1 binding. (PMID:22331897)
• Over-expression of NELL1 is associated with alveolar rhabdomyosarcoma. (PMID:22415709)
• findings suggest that clearance of apoptotic cells in living vertebrates is accomplished by the combined actions of apoptotic cell migration and elmo1-dependent macrophage engulfment (PMID:22503503)
• genetic association study in population in China: Data suggest that 2 SNPs in ELMO1 (rs741301; rs10951509) are associated with diabetic nephropathy in Chinese subjects with type 2 diabetes. (PMID:22842811)
• Analysis of SNP databases of Japanese patuients with diabetic nephropathy revealed ELMO1 as a gene related to the above-cited diabetic complication. (PMID:23156397)
• ELMO1 mutations are associated with esophageal adenocarcinoma. (PMID:23525077)
• findings indicate that a chemokine-controlled pathway, consisting of Galphai2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis (PMID:23591873)
• For ELMO1 (+9170 G>A), the GG genotype frequency was higher in the diabetic versus control group, but there were no differences between diabetic patients with and without nephropathies. (PMID:24433479)
• High ELMO1 expression is associated with serous ovarian cancer. (PMID:24819662)
• findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes. (PMID:24821968)
• There is a low frequency rate of the ancestral genotype for the ELMO1 polymorphism rs1345365 in mestizos from the western and southeastern regions of Mexico. (PMID:25167351)
• high ELMO1 expression is an independent negative prognostic factor in normal karyotype (NK) acute myeloid leukemia. (PMID:25360637)
• Thus, Elmo1 and Dock180 facilitate blood vessel formation by stabilization of the endothelium during angiogenesis. (PMID:25586182)
• ELMO1 is expressed in rheumatoid arthritis synovium, promotes cell migration and invasion, and regulates Rac1 activity, thereby mediating rheumatoid arthritis pathogenicity. (PMID:25901943)
• Src-mediated Y724 phosphorylation in ELMO1 plays a critical role for cell spreading via activation of Rac1, leading to promotion of cell migration. (PMID:26205662)
• Cdc27 is a novel binding partner of Elmo1.Cdc27-Elmo1 has a cellular role independent from the Elmo-Dock1-Rac signal module. (PMID:26882976)
• A significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians. (PMID:27699784)
• ELMO1 genetic variation is associated with with type 2 diabetes. (PMID:28752301)
• FE65 is found to activate ELMO1 by diminishing ELMO1 intramolecular autoinhibitory interaction and to promote the targeting of ELMO1 to the plasma membrane, where Rac1 is activated. We also show that FE65, ELMO1, and DOCK180 form a tripartite complex (PMID:29615491)
• This study revealed the association of the SNP rs1345365 of the ELMO1 gene in a Mexican population (PMID:29938964)
• Study data identify ’noncanonical’ roles for ELMO1 as an important cytoplasmic regulator of specific neutrophil receptors and promoter of arthritis. (PMID:30643265)
• Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study. (PMID:31909452)
• Association of ELMO1 gene polymorphism and diabetic nephropathy among Egyptian patients with type 2 diabetes mellitus. (PMID:32043290)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-56f14.7	ENSDARG00000055400
danio_rerio	elmo1	ENSDARG00000098753
mus_musculus	Elmo1	ENSMUSG00000041112
rattus_norvegicus	Elmo1	ENSRNOG00000059705

Paralogs (5): ELMO2 (ENSG00000062598), ELMO3 (ENSG00000102890), ELMOD1 (ENSG00000110675), ELMOD3 (ENSG00000115459), ELMOD2 (ENSG00000179387)

Protein

Protein identifiers

Engulfment and cell motility protein 1 — Q92556 (reviewed: Q92556)

Alternative names: Protein ced-12 homolog

All UniProt accessions (9): Q92556, A4D1X5, C9IZR8, C9J5X3, C9JB20, C9JIW2, H7C0N5, H7C0S6, H7C3P3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1.

Subunit / interactions. Interacts with ADGRB1. Interacts directly with the SH3-domain of DOCK1 via its SH3-binding site. Part of a complex with DOCK1 and RAC1. Part of a complex with DOCK1 and CRK isoform CRK-II. Interacts with PLEKHG6. Interacts with HCK (via SH3 domain). Interacts with ADGRB3. Interacts with DOCK5.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Widely expressed, with a higher expression in the spleen and placenta.

Post-translational modifications. Phosphorylated by HCK.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92556-1	1	yes
Q92556-2	2
Q92556-3	3

RefSeq proteins (5): NP_001034548, NP_001193409, NP_001193411, NP_055615, NP_569709 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR006816	ELMO_dom	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR024574	ELMO_ARM	Domain
IPR050868	ELMO_domain-containing	Family

Pfam: PF04727, PF11841, PF16457

UniProt features (43 total): strand 12, helix 12, modified residue 8, splice variant 3, domain 2, turn 2, chain 1, sequence variant 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
7Y4A	X-RAY DIFFRACTION	1.6
3A98	X-RAY DIFFRACTION	2.1
2VSZ	X-RAY DIFFRACTION	2.3
7DPA	ELECTRON MICROSCOPY	3.8
6TGC	ELECTRON MICROSCOPY	4.1
8ZJI	ELECTRON MICROSCOPY	4.23
8ZJJ	ELECTRON MICROSCOPY	4.23
8ZJK	ELECTRON MICROSCOPY	4.23
8ZJL	ELECTRON MICROSCOPY	4.31
8ZJM	ELECTRON MICROSCOPY	4.52
8ZJ2	ELECTRON MICROSCOPY	4.66
8JHK	ELECTRON MICROSCOPY	4.76
8XM7	ELECTRON MICROSCOPY	4.91
6TGB	ELECTRON MICROSCOPY	5.5
9LX0	ELECTRON MICROSCOPY	6.98
9LXH	ELECTRON MICROSCOPY	7.52
2RQR	SOLUTION NMR
6JPP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92556-F1	88.95	0.68

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 (8): 511, 720, 18, 100, 105, 216, 344, 395

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-164944	Nef and signal transduction
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-8849471	PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-9958810	SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)

MSigDB gene sets: 299 (showing top): GOBP_REGULATION_OF_VASCULOGENESIS, FREAC2_01, REACTOME_INNATE_IMMUNE_SYSTEM, MODULE_571, GGGNRMNNYCAT_UNKNOWN, PID_NETRIN_PATHWAY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, AREB6_03, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, ROVERSI_GLIOMA_COPY_NUMBER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, TAL1ALPHAE47_01, LHX3_01

GO Biological Process (9): phagocytosis, engulfment (GO:0006911), apoptotic process (GO:0006915), actin filament organization (GO:0007015), Rac protein signal transduction (GO:0016601), actin cytoskeleton organization (GO:0030036), cell motility (GO:0048870), regulation of postsynapse assembly (GO:0150052), phagocytosis (GO:0006909), actin filament-based process (GO:0030029)

GO Molecular Function (3): SH3 domain binding (GO:0017124), guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), guanyl-nucleotide exchange factor complex (GO:0032045), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
The role of Nef in HIV-1 replication and disease pathogenesis	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by VEGF	1
Signaling by PTK6	1
Leishmania phagocytosis	1
Activation of STAT3 by cadherin engagement	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	2
synapse	2
phagocytosis	1
plasma membrane invagination	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
small GTPase-mediated signal transduction	1
cytoskeleton organization	1
actin filament-based process	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
endocytosis	1
protein domain specific binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

1276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELMO1	DOCK1	Q14185	999
ELMO1	WDR35	Q9P2L0	986
ELMO1	DOCK2	Q92608	984
ELMO1	CRK	P46108	970
ELMO1	RHOG	P35238	958
ELMO1	GULP1	Q9UBP9	893
ELMO1	ADGRB1	O14514	871
ELMO1	MACF1	Q9UPN3	784
ELMO1	RAC2	P15153	740
ELMO1	ZNF385B	Q569K4	719
ELMO1	ARL4A	P40617	677
ELMO1	DHX8	Q14562	661
ELMO1	ADGRB3	O60242	634
ELMO1	AKT1	P31749	633
ELMO1	STAB2	Q8WWQ8	632

IntAct

62 interactions, top by confidence:

A	B	Type	Score
DOCK1	ELMO1	psi-mi:“MI:0915”(physical association)	0.940
ELMO1	DOCK1	psi-mi:“MI:0915”(physical association)	0.940
ELMO1	DOCK1	psi-mi:“MI:0914”(association)	0.940
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
ZNF398	ELMO1	psi-mi:“MI:0915”(physical association)	0.800
ELMO1	ZNF398	psi-mi:“MI:0915”(physical association)	0.800
RAC1	DOCK1	psi-mi:“MI:0914”(association)	0.730
RAC1	DOCK1	psi-mi:“MI:0915”(physical association)	0.730
RHOG	ELMO1	psi-mi:“MI:0915”(physical association)	0.620
ELMO1	RHOG	psi-mi:“MI:0915”(physical association)	0.620
ELMO1	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	ELMO1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (84): TRIM54 (Two-hybrid), ZNF398 (Two-hybrid), DOCK4 (Affinity Capture-MS), DOCK3 (Affinity Capture-MS), USP4 (Affinity Capture-MS), MED31 (Affinity Capture-MS), DOCK5 (Affinity Capture-MS), DOCK1 (Affinity Capture-MS), TTC19 (Affinity Capture-MS), ELMO2 (Affinity Capture-MS), ZNF398 (Affinity Capture-MS), CALML3 (Affinity Capture-MS), ELMO1 (Affinity Capture-MS), RHOG (Two-hybrid), DOCK1 (Two-hybrid)

ESM2 similar proteins: A0A0G2JTR4, A1A4S6, A2AWA9, A4FUD6, A4II46, A6H6A9, A6QNS3, A6QQZ7, O60890, P09851, P0CAX5, P20936, P23727, P26450, P27986, P50904, Q08DP6, Q12979, Q5R372, Q5R5M3, Q5R685, Q5R6F2, Q5R8I6, Q5RCC1, Q5RCW6, Q5SSL4, Q5T2T1, Q5U2Y3, Q5ZJ17, Q5ZLX4, Q5ZMW5, Q62696, Q63787, Q6Y5D8, Q6ZQ82, Q7YQL5, Q7YQL6, Q8AVG0, Q8BPU7, Q8K0F1

Diamond homologs: A4FUD6, A6QR40, Q499U2, Q5RCC1, Q8BHL5, Q8BPU7, Q8BYZ7, Q92556, Q96BJ8, Q96JJ3, Q55GR7

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
HCK	up-regulates	ELMO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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
Regulation of signaling by CBL	6	119.2×	1e-09
Downstream signal transduction	5	76.1×	3e-07
FCGR3A-mediated phagocytosis	6	44.9×	3e-07
Regulation of actin dynamics for phagocytic cup formation	5	36.8×	8e-06
VEGFA-VEGFR2 Pathway	5	27.9×	2e-05
Constitutive Signaling by Aberrant PI3K in Cancer	5	25.4×	3e-05
RAC2 GTPase cycle	5	25.4×	3e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	19.4×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of substrate adhesion-dependent cell spreading	6	72.5×	8e-08
cell migration	7	13.9×	6e-05
actin cytoskeleton organization	5	12.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

6171 predictions. Top by Δscore:

Variant	Effect	Δscore
7:36855747:CAGTA:C	acceptor_gain	1.0000
7:36855750:TA:T	acceptor_gain	1.0000
7:36855752:C:CC	acceptor_gain	1.0000
7:36855757:A:T	acceptor_gain	1.0000
7:36861653:CCTTA:C	donor_loss	1.0000
7:36861654:CTTA:C	donor_loss	1.0000
7:36861655:TTACC:T	donor_loss	1.0000
7:36861656:TA:T	donor_loss	1.0000
7:36861658:C:CT	donor_loss	1.0000
7:36872146:T:TA	donor_gain	1.0000
7:36878002:CTACT:C	donor_loss	1.0000
7:36878003:TACTT:T	donor_loss	1.0000
7:36878004:ACTTA:A	donor_loss	1.0000
7:36878006:TTAC:T	donor_loss	1.0000
7:36878007:TACG:T	donor_loss	1.0000
7:36878008:A:AC	donor_gain	1.0000
7:36878009:C:CC	donor_gain	1.0000
7:36878113:CTTGT:C	acceptor_gain	1.0000
7:36878114:TTGT:T	acceptor_gain	1.0000
7:36878118:C:CC	acceptor_gain	1.0000
7:36894847:AACTT:A	donor_loss	1.0000
7:36894848:ACTT:A	donor_loss	1.0000
7:36894849:CTTAC:C	donor_loss	1.0000
7:36894850:TTACA:T	donor_loss	1.0000
7:36894851:TA:T	donor_loss	1.0000
7:36894852:A:AC	donor_gain	1.0000
7:36894853:C:CG	donor_gain	1.0000
7:36894853:CA:C	donor_gain	1.0000
7:36894853:CAA:C	donor_gain	1.0000
7:36894853:CAAA:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008447 (7:37127895 T>C,G), RS1000010386 (7:37374781 G>A), RS1000010874 (7:37055459 A>C), RS1000014685 (7:37179221 A>T), RS1000015939 (7:37120099 T>C), RS1000017004 (7:36919932 C>A,T), RS1000017121 (7:37241810 A>G), RS1000018670 (7:37164402 A>G), RS1000021569 (7:37055288 G>C), RS1000028281 (7:36920156 C>A), RS1000029260 (7:37296377 C>T), RS1000063897 (7:37096983 C>A), RS1000072271 (7:37200599 C>T), RS1000074340 (7:36870532 A>G), RS1000086366 (7:37126625 C>T)

Disease associations

OMIM: gene MIM:606420 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive

Mondo (1): (MONDO:0018393)

Orphanet (0):

HPO phenotypes

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

GWAS associations

53 associations (top):

Study	Trait	p-value
GCST000064_1	Type 2 diabetes nephropathy	8.000000e-06
GCST000323_7	Response to treatment for acute lymphoblastic leukemia	3.000000e-06
GCST000452_13	QT interval	2.000000e-06
GCST000612_5	Celiac disease	2.000000e-07
GCST000987_8	Celiac disease or Rheumatoid arthritis	5.000000e-08
GCST001112_7	Lifetime average cigarettes per day in chronic obstructive pulmonary disease	4.000000e-06
GCST001365_7	Anticoagulant levels	8.000000e-06
GCST001585_12	Breast size	8.000000e-06
GCST001915_20	Alzheimer’s disease (cognitive decline)	1.000000e-06
GCST002738_18	Psoriasis	7.000000e-08
GCST002740_67	Inflammatory skin disease	3.000000e-09
GCST003268_21	Psoriasis vulgaris	3.000000e-06
GCST004069_15	Cerebrospinal fluid AB1-42 levels	5.000000e-06
GCST004069_3	Cerebrospinal fluid AB1-42 levels	7.000000e-06
GCST004363_2	Plasma androstenedione levels in resected early stage-receptor positive breast cancer	3.000000e-07
GCST004599_49	Mean platelet volume	1.000000e-11
GCST004600_32	Eosinophil percentage of white cells	2.000000e-13
GCST004606_152	Eosinophil count	5.000000e-15
GCST004616_185	Platelet distribution width	6.000000e-15
GCST004617_7	Eosinophil percentage of granulocytes	1.000000e-13
GCST004623_107	Neutrophil percentage of granulocytes	6.000000e-13
GCST004624_111	Sum eosinophil basophil counts	7.000000e-15
GCST005523_43	Celiac disease	2.000000e-08
GCST005527_27	Psoriasis	4.000000e-09
GCST005531_47	Multiple sclerosis	6.000000e-14
GCST005569_48	Rheumatoid arthritis	3.000000e-07
GCST005581_38	Primary biliary cirrhosis	2.000000e-07
GCST007932_75	Medication use (thyroid preparations)	4.000000e-10
GCST008154_25	Trunk fat mass	4.000000e-06
GCST008157_22	Body fat mass	8.000000e-06

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004633	protein C measurement
EFO:1001494	psoriasis vulgaris
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0007972	androstenedione measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007984	platelet component distribution width
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0009933	Thyroid preparation use measurement
EFO:0004462	PR interval
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004309	platelet count
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725199 (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

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178976: Inhibition of ELMO1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Aflatoxin B1	decreases expression, decreases methylation, affects expression, affects methylation	4
sodium arsenite	affects methylation, increases expression	3
Valproic Acid	decreases expression, increases expression	3
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	decreases expression, increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
2,4,6-tribromophenol	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation	1
decabromobiphenyl ether	decreases expression	1
arsenite	increases methylation	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
pinostrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	affects response to substance	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697706	Binding	Inhibition of ELMO1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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