MEGF8

multiple EGF like domains 8, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 19:42325609-42378769

Previous symbols: [ "EGFL4", "C19orf49" ]

Links

ENSG00000105429 ∙ NCBI:1954 ∙ OMIM:604267 ∙ HGNC:3233 ∙ Uniprot:Q7Z7M0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• RAB23-related Carpenter syndrome (Definitive), mode of inheritance: AR
• MEGF8-related Carpenter syndrome (Strong), mode of inheritance: AR
• MEGF8-related Carpenter syndrome (Moderate), mode of inheritance: AR
• MEGF8-related Carpenter syndrome (Strong), mode of inheritance: AR
• Carpenter syndrome (Supportive), mode of inheritance: AR
• MEGF8-related Carpenter syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carpenter syndrome 2	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal	23063620

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MEGF8 gene.

• MEGF8-related Carpenter syndrome (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MEGF8 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			5	206	22	233
missense		1	368	29	5	403
nonsense	3	3	1			7
start loss						0
frameshift	2					2
inframe indel		1				1
splice donor/acceptor (+/-2bp)	1	4				5
splice region			6	20	3	29
non coding			3	71	47	121
Total	6	9	377	306	74

Highest pathogenic variant AF is 0.0000197

Variants in MEGF8

This is a list of pathogenic ClinVar variants found in the MEGF8 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-42326085-A-T			Benign (Sep 29, 2019)
19-42326250-C-T		MEGF8-related Carpenter syndrome	Likely benign (Jan 17, 2022)
19-42326270-G-C		MEGF8-related Carpenter syndrome	Uncertain significance (Sep 01, 2021)
19-42326290-C-G		MEGF8-related Carpenter syndrome	Uncertain significance (Mar 24, 2021)
19-42326292-G-C		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
19-42326311-C-T		MEGF8-related Carpenter syndrome	Uncertain significance (Sep 28, 2022)
19-42326320-G-T		MEGF8-related Carpenter syndrome • MEGF8-related disorder	Uncertain significance (Jan 16, 2024)
19-42326355-C-T		MEGF8-related Carpenter syndrome	Uncertain significance (Jul 06, 2022)
19-42326366-A-G		MEGF8-related Carpenter syndrome	Likely benign (Mar 19, 2022)
19-42326368-G-T		Inborn genetic diseases	Uncertain significance (Dec 13, 2022)
19-42326378-G-A		MEGF8-related disorder	Likely benign (May 23, 2019)
19-42326415-G-A		MEGF8-related Carpenter syndrome	Uncertain significance (Apr 19, 2022)
19-42326421-C-G		Inborn genetic diseases	Uncertain significance (May 04, 2022)
19-42333494-A-G			Likely benign (Jul 27, 2020)
19-42333504-A-G			Likely benign (Sep 29, 2019)
19-42333607-C-G		Inborn genetic diseases	Uncertain significance (May 09, 2023)
19-42333663-G-T		MEGF8-related Carpenter syndrome	Likely benign (Jan 18, 2024)
19-42333678-C-T		MEGF8-related Carpenter syndrome	Likely benign (Aug 04, 2023)
19-42333679-G-A		MEGF8-related Carpenter syndrome	Uncertain significance (Feb 19, 2024)
19-42333687-C-T		MEGF8-related disorder	Likely benign (Jan 02, 2020)
19-42333695-C-G		MEGF8-related Carpenter syndrome • Inborn genetic diseases	Uncertain significance (Jul 29, 2022)
19-42333698-C-T		MEGF8-related Carpenter syndrome	Likely benign (Nov 13, 2023)
19-42333699-G-C		MEGF8-related Carpenter syndrome	Likely benign (Nov 08, 2022)
19-42333701-G-A		MEGF8-related Carpenter syndrome	Uncertain significance (Apr 04, 2021)
19-42333704-G-A		MEGF8-related Carpenter syndrome	Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MEGF8	protein_coding	protein_coding	ENST00000334370	41	53161

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000193	1.00	125530	0	64	125594	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.48	1304	1.71e+3	0.763	0.000115	17464
Missense in Polyphen		338	566.73	0.5964		6006
Synonymous	0.768	704	730	0.964	0.0000510	5903
Loss of Function	7.56	35	127	0.276	0.00000693	1306

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000648	0.000599
Ashkenazi Jewish	0.00	0.00
East Asian	0.000225	0.000218
Finnish	0.000151	0.000139
European (Non-Finnish)	0.000328	0.000308
Middle Eastern	0.000225	0.000218
South Asian	0.000199	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a negative regulator of hedgehog signaling. {ECO:0000250|UniProtKB:P60882}.
• Disease: DISEASE: Carpenter syndrome 2 (CRPT2) [MIM:614976]: An autosomal recessive multiple congenital malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet, in association with abnormal left-right patterning and other features, most commonly obesity, umbilical hernia, cryptorchidism, and congenital heart disease. {ECO:0000269|PubMed:23063620}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.696
• rvis_EVS: -4.01
• rvis_percentile_EVS: 0.19

Haploinsufficiency Scores

• pHI: 0.727
• hipred: Y
• hipred_score: 0.520
• ghis: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Megf8
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); craniofacial phenotype; vision/eye phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: megf8
• Affected structure: heart tube
• Phenotype tag: abnormal
• Phenotype quality: position

Gene ontology

• Biological process: embryonic heart tube morphogenesis;regulation of gene expression;embryonic limb morphogenesis;BMP signaling pathway;limb morphogenesis;cell migration involved in gastrulation;negative regulation of smoothened signaling pathway;embryonic skeletal system morphogenesis;positive regulation of axon extension involved in axon guidance;epiboly involved in gastrulation with mouth forming second;embryonic heart tube left/right pattern formation;left/right pattern formation;coronary vasculature development;determination of heart left/right asymmetry;determination of digestive tract left/right asymmetry;craniofacial suture morphogenesis;fasciculation of sensory neuron axon
• Cellular component: nucleus;integral component of membrane;extracellular exosome
• Molecular function: calcium ion binding;protein binding