MEGF10

Summary

MEGF10 (multiple EGF like domains 10, HGNC:29634) is a protein-coding gene on chromosome 5q23.2, encoding Multiple epidermal growth factor-like domains protein 10 (Q96KG7). Membrane receptor involved in phagocytosis by macrophages and astrocytes of apoptotic cells.

This gene encodes a member of the multiple epidermal growth factor-like domains protein family. The encoded protein plays a role in cell adhesion, motility and proliferation, and is a critical mediator of apoptotic cell phagocytosis as well as amyloid-beta peptide uptake in the brain. Expression of this gene may be associated with schizophrenia, and mutations in this gene are a cause of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) as well as congenital myopathy with minicores. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 84466 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MEGF10-related myopathy (Definitive, ClinGen)
• GWAS associations: 10
• Clinical variants (ClinVar): 1,165 total — 32 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 65
• MANE Select transcript: NM_001256545

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29634
Approved symbol	MEGF10
Name	multiple EGF like domains 10
Location	5q23.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1780, SR-F3
Ensembl gene	ENSG00000145794
Ensembl biotype	protein_coding
OMIM	612453
Entrez	84466

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000274473, ENST00000418761, ENST00000503335, ENST00000506709, ENST00000507158, ENST00000508365, ENST00000510513, ENST00000510828, ENST00000515002, ENST00000515622

RefSeq mRNA: 4 — MANE Select: NM_001256545 NM_001256545, NM_001308119, NM_001308121, NM_032446

CCDS: CCDS4142, CCDS78055

Canonical transcript exons

ENST00000503335 — 25 exons

Exon	Start	End
ENSE00000972379	127331291	127331424
ENSE00000972380	127339120	127339221
ENSE00000972381	127340530	127340630
ENSE00000972383	127396532	127396778
ENSE00000972384	127398676	127398796
ENSE00000972385	127402546	127402682
ENSE00000972387	127417638	127417812
ENSE00000972388	127419120	127419240
ENSE00000972389	127420044	127420207
ENSE00000972390	127422670	127422772
ENSE00001082690	127442998	127443126
ENSE00001082693	127445457	127445693
ENSE00001082694	127457128	127461222
ENSE00001082695	127433363	127433509
ENSE00001082697	127440739	127440867
ENSE00001240075	127290796	127291056
ENSE00002470111	127369910	127370002
ENSE00003475097	127455401	127455607
ENSE00003485912	127447557	127447684
ENSE00003493623	127454566	127454610
ENSE00003526686	127434687	127434821
ENSE00003613972	127449099	127449222
ENSE00003620808	127410389	127410601
ENSE00003633910	127438439	127438567
ENSE00003634290	127435361	127435489

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 96.50.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9714 / max 271.3708, expressed in 692 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58328	2.3684	363
58327	1.4378	353
58323	0.5185	311
58325	0.3442	160
58326	0.1351	85
58324	0.0988	55
58333	0.0686	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	96.50	gold quality
ventricular zone	UBERON:0003053	96.19	gold quality
lateral globus pallidus	UBERON:0002476	96.11	gold quality
inferior vagus X ganglion	UBERON:0005363	95.75	gold quality
globus pallidus	UBERON:0001875	95.08	gold quality
endothelial cell	CL:0000115	95.06	gold quality
subthalamic nucleus	UBERON:0001906	94.72	gold quality
medial globus pallidus	UBERON:0002477	94.68	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.63	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.23	gold quality
tibia	UBERON:0000979	93.14	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.99	gold quality
medulla oblongata	UBERON:0001896	92.93	gold quality
superior vestibular nucleus	UBERON:0007227	91.58	gold quality
ventral tegmental area	UBERON:0002691	90.79	gold quality
substantia nigra pars compacta	UBERON:0001965	90.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.21	gold quality
entorhinal cortex	UBERON:0002728	90.19	gold quality
pons	UBERON:0000988	89.43	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.23	gold quality
postcentral gyrus	UBERON:0002581	88.65	gold quality
parietal lobe	UBERON:0001872	88.53	gold quality
occipital lobe	UBERON:0002021	88.02	gold quality
primary visual cortex	UBERON:0002436	87.34	gold quality
ganglionic eminence	UBERON:0004023	86.88	gold quality
spinal cord	UBERON:0002240	86.66	gold quality
midbrain	UBERON:0001891	86.13	gold quality
middle temporal gyrus	UBERON:0002771	86.07	gold quality
superior frontal gyrus	UBERON:0002661	86.03	gold quality
temporal lobe	UBERON:0001871	85.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYOG

miRNA regulators (miRDB)

166 targeting MEGF10, 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-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 17)

• in a system of forced expression by transfection, MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7 (PMID:17205124)
• Human MEGF10 is an ortholog of Ced1. (PMID:17498693)
• An interaction between MEGF10 and clathrin assembly protein complex 2 medium chain (AP50), a component of clathrin-coated pits was identified. (PMID:17643423)
• In expression studies, MEGF10 had higher expression levels in the affected than the unaffected (p = .015). Schizophrenia patients with a 1/1 genotype at rs27388 had higher expressions than those patients with 1/2 and 2/2 genotypes (p = .0008). (PMID:18179784)
• The results of this study suggested that no association between schizophrenia and rs27388 of the MEGF10 gene in Chinese case-control sample. (PMID:20813413)
• MEGF10 is involved in the uptake of amyloid-beta peptide (Abeta42) in the brain. (PMID:20828568)
• Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) (PMID:22101682)
• Megf10 is required for preserving the undifferentiated, proliferative potential of satellite cells, myogenic precursors that regenerate skeletal muscle in response to injury or disease. (PMID:22371254)
• Mutations in MEGF10 cause a recessive congenital myopathy with minicores and suggest satellite cell dysfunction as the pathogenic mechanism (PMID:22371254)
• results indicate that myogenin is a positive regulator in transcriptional regulation of MEGF10 in skeletal muscle (PMID:25044114)
• MEGF10 mutations can cause myopathy with adult-onset respiratory insufficiency (PMID:26802438)
• Concentrating on hypermethylated genes to identify candidate tumor suppressor loci, the study found the cell engulfment and adhesion factor gene MEGF10 to be epigenetically repressed by DNA hypermethylation or by H3K27/K9 methylation in neuroblastoma cell lines. (PMID:27862318)
• Findings indicate that the risk alleles and haplotype near the multiple epidermal growth factor-like-domains 10 (MEGF10) transcription start site (TSS) might modulate transcriptional activity and increase the susceptibility to autism. (PMID:28536440)
• Results suggested that methylation level and mRNA expression of MEGF10 in glioma were not only correlated with IDH mutation but also associated with clinical outcome of patients. (PMID:29887919)
• ZNF667-AS1, a positively regulating MEGF10, inhibits the progression of uveal melanoma by modulating cellular aggressiveness. (PMID:33512044)
• Phenotypic Variability of MEGF10 Variants Causing Congenital Myopathy: Report of Two Unrelated Patients from a Highly Consanguineous Population. (PMID:34828389)
• [A family with early onset myopathy caused by MEGF10 gene defect and literature review]. (PMID:36849355)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	megf10	ENSDARG00000017229
mus_musculus	Megf10	ENSMUSG00000024593
rattus_norvegicus	Megf10	ENSRNOG00000013674

Paralogs (3): MEGF11 (ENSG00000157890), MEGF6 (ENSG00000162591), GAS6 (ENSG00000183087)

Protein

Protein identifiers

Multiple epidermal growth factor-like domains protein 10 — Q96KG7 (reviewed: Q96KG7)

All UniProt accessions (1): Q96KG7

UniProt curated annotations — full annotation on UniProt →

Function. Membrane receptor involved in phagocytosis by macrophages and astrocytes of apoptotic cells. Receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the surface of apoptotic cells. Cooperates with ABCA1 within the process of engulfment. Promotes the formation of large intracellular vacuoles and may be responsible for the uptake of amyloid-beta peptides. Necessary for astrocyte-dependent apoptotic neuron clearance in the developing cerebellum. Plays role in muscle cell proliferation, adhesion and motility. Is also an essential factor in the regulation of myogenesis. Controls the balance between skeletal muscle satellite cells proliferation and differentiation through regulation of the notch signaling pathway (PubMed:28498977, Ref.16). May also function in the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion. Mosaics provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements.

Subunit / interactions. Homomer. Interacts with GULP1 and ABCA1. Interacts with AP2M1. Does not interact with MEGF11. Binds with high affinity to complement C1q. Interacts (via the cytoplasmic domain) with NOTCH1 (via NICD domain).

Subcellular location. Cell membrane. Cell projection. Phagocytic cup.

Tissue specificity. Expressed in muscle (at protein level).

Post-translational modifications. Phosphorylated on tyrosine residues. Phosphorylation at Tyr-1030 may be important for muscle cell proliferation. Ubiquitinated; mono- and polyubiquitinated forms are detected.

Disease relevance. Congenital myopathy 10A, severe variant (CMYO10A) [MIM:614399] An autosomal recessive congenital myopathy characterized by onset at birth, or early in infancy, of respiratory distress caused by diaphragmatic weakness. Additional features are dysphagia resulting in poor feeding, failure to thrive, poor head control, facial weakness, cleft palate, contractures and scoliosis. Affected individuals become ventilator-dependent, and most require feeding by gastrostomy. The disorder results in severe muscle weakness and most patients never achieve walking. Death from respiratory failure in childhood occurs in about half of patients. Muscle biopsies from affected individuals show myopathic changes, replacement of myofibers with fatty tissue, small and incompletely fused muscle fibers, and variation in fiber size. Short regions of sarcomeric disorganization with few or no mitochondria (minicores) have been observed in some cases. The disease is caused by variants affecting the gene represented in this entry. Congenital myopathy 10B, mild variant (CMYO10B) [MIM:620249] An autosomal recessive skeletal muscle disorder characterized by infantile or childhood onset of proximal and distal weakness of upper and lower limbs, facial weakness, areflexia, dysphagia, and respiratory distress. Muscle biopsy shows myopathic changes including type 1 fiber predominance, minicore lesions, and myofibrillar disorganization. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The EMI and EGF-like domains work in concert to promote self-assembly.

Similarity. Belongs to the MEGF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96KG7-1	1	yes
Q96KG7-2	2

RefSeq proteins (4): NP_001243474, NP_001295048, NP_001295050, NP_115822 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002049	LE_dom	Domain
IPR011489	EMI_domain	Domain
IPR013032	EGF-like_CS	Conserved_site
IPR013111	EGF_extracell	Domain
IPR052485	MEGF_diff_regulators	Family
IPR057138	EGF_PEAR1L-like	Domain

Pfam: PF00053, PF07974, PF12661, PF23301

UniProt features (93 total): disulfide bond 48, domain 16, sequence variant 10, mutagenesis site 4, region of interest 3, topological domain 2, glycosylation site 2, splice variant 2, signal peptide 1, chain 1, compositionally biased region 1, modified residue 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KG7-F1	70.73	0.01

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 (1): 1030

Disulfide bonds (48): 34–95, 60–69, 94–105, 109–118, 113–124, 126–135, 148–160, 154–167, 169–178, 191–203, 197–210, 212–221, 234–246, 240–253, 255–264, 281–289, 283–296, 298–307, 320–332, 326–339 …

Glycosylation sites (2): 134, 496

Mutagenesis-validated functional residues (4):

Position	Phenotype
927	does not interact with gulp1; when associated with a-930.
930	does not interact with gulp1; when associated with a-927.
1030	enhances cell proliferation.
1030	abolishes tyrosine phosphorylation. unable to enhance cell proliferation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 296 (showing top): GOBP_REGULATION_OF_SKELETAL_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MUSCLE_CELL_PROLIFERATION, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, ROZANOV_MMP14_TARGETS_UP, GOBP_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, INGRAM_SHH_TARGETS_DN, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT

GO Biological Process (21): skeletal muscle satellite cell activation (GO:0014719), skeletal muscle satellite cell differentiation (GO:0014816), skeletal muscle satellite cell proliferation (GO:0014841), positive regulation of cell-cell adhesion (GO:0022409), muscle cell proliferation (GO:0033002), homotypic cell-cell adhesion (GO:0034109), apoptotic cell clearance (GO:0043277), engulfment of apoptotic cell (GO:0043652), recognition of apoptotic cell (GO:0043654), myoblast development (GO:0048627), regulation of skeletal muscle tissue development (GO:0048641), regulation of muscle cell differentiation (GO:0051147), myoblast migration (GO:0051451), muscle cell development (GO:0055001), apoptotic process involved in development (GO:1902742), positive regulation of myoblast proliferation (GO:2000288), phagocytosis (GO:0006909), cell adhesion (GO:0007155), muscle organ development (GO:0007517), vesicle-mediated transport (GO:0016192), cell development (GO:0048468)

GO Molecular Function (4): complement component C1q complex binding (GO:0001849), scavenger receptor activity (GO:0005044), Notch binding (GO:0005112), protein binding (GO:0005515)

GO Cellular Component (4): phagocytic cup (GO:0001891), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell-cell adhesion	2
apoptotic cell clearance	2
cell development	2
muscle cell differentiation	2
cellular process	2
cell activation	1
skeletal muscle cell differentiation	1
skeletal muscle cell proliferation	1
regulation of cell-cell adhesion	1
positive regulation of cell adhesion	1
cell population proliferation	1
phagocytosis	1
phagocytosis, engulfment	1
phagocytosis, recognition	1
myoblast differentiation	1
skeletal muscle tissue development	1
regulation of striated muscle tissue development	1
regulation of cell differentiation	1
muscle cell migration	1
apoptotic process	1
anatomical structure development	1
positive regulation of cell population proliferation	1
myoblast proliferation	1
regulation of myoblast proliferation	1
endocytosis	1
animal organ development	1
muscle structure development	1
transport	1
opsonin binding	1
complement binding	1
protein-containing complex binding	1
cargo receptor activity	1
signaling receptor binding	1
binding	1
plasma membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEGF10	IFT122	Q9HBG6	858
MEGF10	CCDC136	Q96JN2	825
MEGF10	MERTK	Q12866	794
MEGF10	GULP1	Q9UBP9	793
MEGF10	ADGRB1	O14514	676
MEGF10	EGF	P01133	675
MEGF10	AP2M1	P20172	635
MEGF10	SPATA6	Q9NWH7	631
MEGF10	DOCK1	Q14185	596
MEGF10	CRK	P46108	559
MEGF10	AP2B1	P21851	554
MEGF10	CCDC78	A2IDD5	544
MEGF10	AP2A1	O95782	544
MEGF10	SPARCL1	Q14515	542
MEGF10	ELMO3	Q96BJ8	539

IntAct

28 interactions, top by confidence:

A	B	Type	Score
MEGF10	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
MEGF10	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	CUL7	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	CEP57	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	SART3	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	HDAC4	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	ALMS1	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	HSPA12A	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	VWA8	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	ARHGAP32	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	MCF2L2	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	TAOK2	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	BAHD1	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	ITSN2	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	AARS2	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	ZNFX1	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	SCAPER	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	RACGAP1	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	TMEM132A	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	CADPS2	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	SHTN1	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	AP2M1	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	GRB10	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	DHX16	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	SNRNP200	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	RANBP10	psi-mi:“MI:0915”(physical association)	0.370
FYN	MEGF10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): SYK (Affinity Capture-Western), MEGF10 (Affinity Capture-MS), MEGF10 (Proximity Label-MS), TFAP2A (Affinity Capture-MS), TFAP2B (Affinity Capture-MS), AP2M1 (Affinity Capture-MS), VIM (Affinity Capture-MS), GULP1 (Reconstituted Complex), ACTB (Affinity Capture-Western), MEGF10 (Two-hybrid), AP2M1 (Two-hybrid), GRB10 (Two-hybrid), DHX16 (Two-hybrid), SNRNP200 (Two-hybrid), RANBP10 (Two-hybrid)

ESM2 similar proteins: A0JM12, A1A5Y0, A2VCU8, A6BM72, A6QR11, E9QJQ6, O42182, O70534, O88281, P23142, P35555, P35953, P80370, P97607, P98133, P98155, P98156, P98165, P98166, Q08879, Q09163, Q28832, Q2VWQ2, Q5R3Z7, Q5VY43, Q61220, Q61554, Q61555, Q62918, Q62919, Q6DIB5, Q7ZXL5, Q80T14, Q80T91, Q80V70, Q86XX4, Q8C088, Q8R4Y4, Q8VIK5, Q90827

Diamond homologs: A0JM12, A6BM72, A8XMW6, E9QJQ6, Q5ND28, Q5RBP1, Q5VY43, Q6DIB5, Q6UXI9, Q80T91, Q8AVH7, Q8VIK5, Q91V88, Q96KG7, Q9W0A0, Q9XWD6, Q99944, Q8IUX8, Q9JJZ5, P59222, Q14162, Q6AZ60, Q96GP6, A2AJ76, A2RUV0, A2VCU8, A5A8Y8, A6QR11, A8WGB1, B3EWY9, B5DFC9, G3I6Z6, G3V928, O42182, O73775, O75095, O77469, O88322, P10493, P21783

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ABCA1	“up-regulates activity”	MEGF10	binding
MEGF10	“up-regulates activity”	ABCA1	binding
MEGF10	up-regulates	Phagocytosis
SRC	“up-regulates activity”	MEGF10	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1165 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	28
Uncertain significance	582
Likely benign	388
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070845	NM_001256545.2(MEGF10):c.240T>G (p.Tyr80Ter)	Pathogenic
1073582	NM_001256545.2(MEGF10):c.3169A>T (p.Arg1057Ter)	Pathogenic
1351978	NM_001256545.2(MEGF10):c.1518_1528del (p.Cys507fs)	Pathogenic
1452067	NM_001256545.2(MEGF10):c.815del (p.Arg272fs)	Pathogenic
1457177	NM_001256545.2(MEGF10):c.3094del (p.Thr1032fs)	Pathogenic
1906386	NM_001256545.2(MEGF10):c.480C>A (p.Cys160Ter)	Pathogenic
2088364	NM_001256545.2(MEGF10):c.2663C>G (p.Ser888Ter)	Pathogenic
2114793	NM_001256545.2(MEGF10):c.1169del (p.Gly390fs)	Pathogenic
2131505	NM_001256545.2(MEGF10):c.702T>A (p.Cys234Ter)	Pathogenic
2173107	NM_001256545.2(MEGF10):c.241C>T (p.Arg81Ter)	Pathogenic
2443926	NM_001256545.2(MEGF10):c.2981-2A>G	Pathogenic
2443927	NM_001256545.2(MEGF10):c.413_659del247 (p.Cys139fs)	Pathogenic
2443928	NM_001256545.2(MEGF10):c.131_132del (p.Val44fs)	Pathogenic
2443929	NM_001256545.2(MEGF10):c.2429G>A (p.Cys810Tyr)	Pathogenic
2443930	NM_001256545.2(MEGF10):c.352T>C (p.Cys118Arg)	Pathogenic
2443931	NM_001256545.2(MEGF10):c.1426+1G>T	Pathogenic
2860403	NM_001256545.2(MEGF10):c.721C>T (p.Gln241Ter)	Pathogenic
30960	NM_001256545.2(MEGF10):c.2288_2297dup (p.Asp766delinsGluArgSerTer)	Pathogenic
30961	NM_001256545.2(MEGF10):c.1559G>A (p.Trp520Ter)	Pathogenic
30962	NM_001256545.2(MEGF10):c.2301C>A (p.Cys767Ter)	Pathogenic
30963	NM_001256545.2(MEGF10):c.3144T>G (p.Tyr1048Ter)	Pathogenic
30964	NM_001256545.2(MEGF10):c.1325del (p.Pro442fs)	Pathogenic
30966	NM_001256545.2(MEGF10):c.976T>C (p.Cys326Arg)	Pathogenic
3605001	NM_001256545.2(MEGF10):c.44T>A (p.Leu15Ter)	Pathogenic
3655800	NM_001256545.2(MEGF10):c.3158C>A (p.Ser1053Ter)	Pathogenic
3707639	NM_001256545.2(MEGF10):c.24C>A (p.Cys8Ter)	Pathogenic
419378	NM_001256545.2(MEGF10):c.625G>T (p.Glu209Ter)	Pathogenic
4725970	NM_001256545.2(MEGF10):c.1069G>T (p.Glu357Ter)	Pathogenic
643447	NM_001256545.2(MEGF10):c.198delinsACATTC (p.Trp66Ter)	Pathogenic
864627	NM_001256545.2(MEGF10):c.550C>T (p.Gln184Ter)	Pathogenic

SpliceAI

4230 predictions. Top by Δscore:

Variant	Effect	Δscore
5:127334853:A:G	donor_gain	1.0000
5:127339118:A:AG	acceptor_gain	1.0000
5:127339119:G:GA	acceptor_gain	1.0000
5:127339119:GCT:G	acceptor_gain	1.0000
5:127340528:A:AG	acceptor_gain	1.0000
5:127340529:G:GG	acceptor_gain	1.0000
5:127340529:GA:G	acceptor_gain	1.0000
5:127340627:GTCC:G	donor_gain	1.0000
5:127340631:G:GG	donor_gain	1.0000
5:127340635:G:GG	donor_gain	1.0000
5:127396774:GCCTT:G	donor_gain	1.0000
5:127410379:T:A	acceptor_gain	1.0000
5:127410383:T:A	acceptor_gain	1.0000
5:127410388:G:C	acceptor_loss	1.0000
5:127410388:G:GT	acceptor_gain	1.0000
5:127410388:GGT:G	acceptor_gain	1.0000
5:127410599:TAG:T	donor_gain	1.0000
5:127410602:G:GC	donor_loss	1.0000
5:127410602:G:GG	donor_gain	1.0000
5:127410603:T:G	donor_loss	1.0000
5:127417637:GCT:G	acceptor_gain	1.0000
5:127417785:A:T	donor_gain	1.0000
5:127417813:G:GG	donor_gain	1.0000
5:127433505:GAGGA:G	donor_gain	1.0000
5:127433506:AGGA:A	donor_gain	1.0000
5:127433507:GGA:G	donor_gain	1.0000
5:127433507:GGAG:G	donor_gain	1.0000
5:127433508:GA:G	donor_gain	1.0000
5:127433508:GAG:G	donor_gain	1.0000
5:127433508:GAGTA:G	donor_loss	1.0000

AlphaMissense

7537 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:127331419:G:C	W37C	0.999
5:127331419:G:T	W37C	0.999
5:127369980:G:C	W130C	0.999
5:127369980:G:T	W130C	0.999
5:127398678:G:A	C221Y	0.999
5:127398689:T:C	C225R	0.999
5:127398707:G:T	G231C	0.999
5:127398773:T:A	C253S	0.999
5:127398773:T:C	C253R	0.999
5:127398774:G:C	C253S	0.999
5:127398793:G:C	W259C	0.999
5:127398793:G:T	W259C	0.999
5:127402546:G:T	G261C	0.999
5:127402555:T:A	C264S	0.999
5:127402555:T:C	C264R	0.999
5:127402556:G:A	C264Y	0.999
5:127402556:G:C	C264S	0.999
5:127402556:G:T	C264F	0.999
5:127402557:T:G	C264W	0.999
5:127402596:T:G	C277W	0.999
5:127433372:G:A	C568Y	0.999
5:127433373:T:G	C568W	0.999
5:127433482:G:T	G605C	0.999
5:127433500:T:C	C611R	0.999
5:127433501:G:A	C611Y	0.999
5:127433502:T:G	C611W	0.999
5:127434690:G:A	C615Y	0.999
5:127434691:C:G	C615W	0.999
5:127438458:G:C	W708C	0.999
5:127438458:G:T	W708C	0.999

dbSNP variants (sampled 300 via entrez): RS1000009951 (5:127328257 C>G,T), RS1000013545 (5:127283586 A>G), RS1000033244 (5:127348121 T>C), RS1000039110 (5:127246026 T>A), RS1000066388 (5:127370461 T>G), RS1000071950 (5:127410917 C>T), RS1000084558 (5:127305008 T>G), RS1000091782 (5:127334673 T>C), RS1000102143 (5:127417560 G>A), RS1000115554 (5:127283295 T>C), RS1000134806 (5:127417305 G>A,T), RS1000139065 (5:127243403 A>C,G), RS1000153056 (5:127389805 A>G), RS1000159696 (5:127291929 A>G), RS1000168746 (5:127290485 G>T)

Disease associations

OMIM: gene MIM:612453 | disease phenotypes: MIM:614399, MIM:620249

GenCC curated gene-disease

Disease	Classification	Inheritance
MEGF10-related myopathy	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MEGF10-related myopathy	Definitive	AR

Mondo (2): MEGF10-related myopathy (MONDO:0013731), congenital myopathy 10b, mild variant (MONDO:0859515)

Orphanet (1): Early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome (Orphanet:439212)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000467	Neck muscle weakness
HP:0000767	Pectus excavatum
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001308	Tongue fasciculations
HP:0001319	Neonatal hypotonia
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0001611	Hypernasal speech
HP:0001762	Talipes equinovarus
HP:0001771	Achilles tendon contracture
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002098	Respiratory distress
HP:0002421	Poor head control
HP:0002650	Scoliosis
HP:0002878	Respiratory failure
HP:0003200	Ragged-red muscle fibers
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003307	Hyperlordosis

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001915_12	Alzheimer’s disease (cognitive decline)	8.000000e-07
GCST005023_12	Initial pursuit acceleration	8.000000e-06
GCST006292_1	Response to antipsychotic treatment in schizophrenia	1.000000e-09
GCST006292_8	Response to antipsychotic treatment in schizophrenia	2.000000e-06
GCST008534_1	Hearing loss in Charcot-Marie-Tooth disease 1A	2.000000e-07
GCST008939_1	Chromosomal aberration frequency (chromosome type) in genotoxic compound exposure	3.000000e-06
GCST009378_1	Bone mineral content	2.000000e-06
GCST009378_16	Bone mineral content	6.000000e-07
GCST009378_23	Bone mineral content	2.000000e-06
GCST90000025_6	Appendicular lean mass	2.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008434	initial pursuit acceleration
EFO:0009861	chromosome-type aberration frequency
EFO:0007621	bone mineral content measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	5
methylmercuric chloride	decreases expression, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	increases methylation, affects cotreatment	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	1
quinocetone	increases expression	1
dorsomorphin	increases expression, decreases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Carbamazepine	affects expression	1
Cytarabine	increases expression	1
Fonofos	increases methylation	1
Estradiol	increases expression, affects cotreatment	1
Lipopolysaccharides	affects response to substance, increases expression	1
Parathion	increases methylation	1
Progesterone	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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