ELMO2

protein-coding

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

Gene summary

The protein encoded by this gene interacts with the dedicator of cyto-kinesis 1 protein. Similarity to a C. elegans protein suggests that this protein may function in phagocytosis of apoptotic cells and in cell migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MANE transcript

NM_133171.5

Inheritance

ClinVar variants

P:7U:69B:13

Top phenotype

Vascular malformation, primary intraosseus

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr20:46,366,050-46,432,985

External References & Databases

Ensembl (ENSG00000062598)

Transcript & Mutation Effects

hg38 • Region Span ~66.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary intraosseous venous malformationSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011744

Submitter: Orphanet

Ramon syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009954

Submitter: Orphanet

primary intraosseous venous malformationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011744

Submitter: Labcorp Genetics (formerly Invitae)

primary intraosseous venous malformationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011744

Submitter: G2P

primary intraosseous venous malformationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011744

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Vascular malformation, primary intraosseusAR

Manifestation: Cardiovascular; Musculoskeletal

Intervention: Cardiovascular

Rationale: 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

Refs: 11932989; 27476657

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ELMO2 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 58

Primary intraosseous venous malformationTotal: 15

not providedTotal: 11

ELMO2-related disorderTotal: 8

not specifiedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133171.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	11 clinvar	1 clinvar	14
missense			62 clinvar	1 clinvar		63
nonsense		2 clinvar				2
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	5 clinvar			8
Total	4	3	69	12	1	89

Highest pathogenic variant AF is 0.000004338556

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133171.5	RefSeq	NP_573403.1	20	MANE Select
ENST00000290246.11	Ensembl	ENSP00000290246.6	20	MANE Select
NM_001318253.2	RefSeq	NP_001305182.1	16	Standard
NM_182764.3	RefSeq	NP_877496.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bacterial invasion of epithelial cells - Homo sapiens (human)
Shigellosis - Homo sapiens (human)
Signaling by PTK6
Signal Transduction
VEGFA-VEGFR2 Pathway

Biological Process

apoptotic process
cytoskeleton organization
Fc-gamma receptor signaling pathway involved in phagocytosis
vascular endothelial growth factor receptor signaling pathway
cell chemotaxis

Molecular Function

protein binding
SH3 domain binding
receptor tyrosine kinase binding

Cellular Component

cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290246
Coding exons: 20
Length: 67017
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.27	235	425	0.553	0.0000243	4791
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.000067	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.725
RVIS EVS: -0.82
RVIS percentile EVS: 11.77

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.661

Gene Damage Prediction

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