ELMO2

engulfment and cell motility 2, the group of Engulfment and cell motility proteins

Basic information

Region (hg38): 20:46366050-46432985

Links

ENSG00000062598 ∙ NCBI:63916 ∙ OMIM:606421 ∙ HGNC:17233 ∙ Uniprot:Q96JJ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ramon syndrome (Supportive), mode of inheritance: AR
• primary intraosseous venous malformation (Supportive), mode of inheritance: AR
• primary intraosseous venous malformation (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vascular malformation, primary intraosseus	AR	Cardiovascular	The condition involves vascular malformation often affecting the vertebral column and the skull, with life-threatening complications after tooth extraction as well as spontaneous severe bleeding episodes, and awareness may allow preventive measures and aggressive management, which may ameliorate morbidity and mortality	Cardiovascular; Musculoskeletal	11932989; 27476657

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ELMO2 gene.

• Primary intraosseous venous malformation (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ELMO2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	2	9
missense			17			17
nonsense		2				2
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region				3		3
non coding				2	17	19
Total	2	3	17	9	19

Variants in ELMO2

This is a list of pathogenic ClinVar variants found in the ELMO2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-46367392-T-C		Inborn genetic diseases	Uncertain significance (Oct 25, 2024)
20-46367442-AG-A		Primary intraosseous venous malformation	Pathogenic (Sep 13, 2016)
20-46367455-G-A		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
20-46367515-T-C		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
20-46367543-A-G		Primary intraosseous venous malformation	Benign (Jul 30, 2021)
20-46367615-C-A			Benign (May 12, 2021)
20-46367666-A-G			Benign (May 11, 2021)
20-46368695-GC-G			Benign (May 11, 2021)
20-46368966-C-G		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
20-46369063-C-T			Benign (May 12, 2021)
20-46369117-G-A			Benign (May 11, 2021)
20-46370389-T-C			Benign (May 12, 2021)
20-46370408-C-A			Benign (May 20, 2021)
20-46370526-C-G		Primary intraosseous venous malformation	Likely pathogenic (Jul 16, 2020)
20-46370638-A-G			Benign (May 12, 2021)
20-46371319-A-G			Benign (May 12, 2021)
20-46371382-C-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
20-46371680-T-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
20-46371688-C-G		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
20-46371783-G-C			Benign (May 12, 2021)
20-46371861-G-A		Primary intraosseous venous malformation	Likely pathogenic (Jun 12, 2024)
20-46371916-G-T		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
20-46371939-G-A		Primary intraosseous venous malformation	Likely pathogenic (Nov 06, 2021)
20-46371942-T-C		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
20-46371951-C-G		Inborn genetic diseases	Uncertain significance (Dec 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ELMO2	protein_coding	protein_coding	ENST00000290246	20	67017

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000104	1.00	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.27	235	425	0.553	0.0000243	4791
Missense in Polyphen		23	101.66	0.22624		1176
Synonymous	-0.446	162	155	1.05	0.00000845	1339
Loss of Function	3.95	17	45.8	0.371	0.00000286	461

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.0000544	0.0000544
Finnish	0.0000473	0.0000462
European (Non-Finnish)	0.0000969	0.0000967
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000672	0.0000653
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:11595183, ECO:0000269|PubMed:11703939, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:27476657}.
• Pathway: Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Signaling by PTK6;Signal Transduction;VEGFA-VEGFR2 Pathway;Fcgamma receptor (FCGR) dependent phagocytosis;Innate Immune System;Immune System;EGFR1;Regulation of actin dynamics for phagocytic cup formation;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;Signaling by Non-Receptor Tyrosine Kinases;Signaling by VEGF;Integrin-linked kinase signaling;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.725
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.77

Haploinsufficiency Scores

• pHI: 0.279
• hipred: Y
• hipred_score: 0.648
• ghis: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.661

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Elmo2

Gene ontology

• Biological process: apoptotic process;cytoskeleton organization;Fc-gamma receptor signaling pathway involved in phagocytosis;vascular endothelial growth factor receptor signaling pathway;cell chemotaxis;cell-cell adhesion
• Cellular component: cytosol;membrane
• Molecular function: protein binding;SH3 domain binding;receptor tyrosine kinase binding