EFEMP2

EGF containing fibulin extracellular matrix protein 2, the group of Fibulins

Basic information

Region (hg38): 11:65866440-65873592

Links

ENSG00000172638 ∙ NCBI:30008 ∙ OMIM:604633 ∙ HGNC:3219 ∙ Uniprot:O95967 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cutis laxa, autosomal recessive, type 1B (Definitive), mode of inheritance: AR
• cutis laxa, autosomal recessive, type 1B (Strong), mode of inheritance: AR
• cutis laxa, autosomal recessive, type 1B (Strong), mode of inheritance: AR
• cutis laxa, autosomal recessive, type 1B (Strong), mode of inheritance: AR
• autosomal recessive cutis laxa type 1 (Supportive), mode of inheritance: AR
• lethal arteriopathy syndrome due to fibulin-4 deficiency (Supportive), mode of inheritance: AR
• familial thoracic aortic aneurysm and aortic dissection (Moderate), mode of inheritance: AR
• cutis laxa, autosomal recessive, type 1B (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cutis laxa, autosomal recessive type IB	AR	Cardiovascular	Manifestations can include cardiovascular anomalies, including aortic dilatation and aortic aneurysms, and surveillance may allow early detection and management (eg, with beta-blockers and angiotensin-receptor inhibitors), which can decrease morbidity and mortality; Cigarette smoking should be avoided due to risk of exacerbation of pulmonary manifestations (including emphysema)	Cardiovascular; Dermatologic; Musculoskeletal; Pulmonary	16685658; 17937443; 19664000; 20389311; 21563328; 22440127; 23212998

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EFEMP2 gene.

• Cutis laxa, autosomal recessive, type 1B (304 variants)
• Cardiovascular phenotype (164 variants)
• not provided (96 variants)
• not specified (33 variants)
• Inborn genetic diseases (9 variants)
• Familial thoracic aortic aneurysm and aortic dissection (8 variants)
• Cutis laxa, autosomal recessive, type 1A (5 variants)
• Cutis laxa, recessive (2 variants)
• EFEMP2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EFEMP2 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			4	109	1	114
missense	3	5	161	3	1	173
nonsense	2					2
start loss						0
frameshift	4	1	2			7
inframe indel			4			4
splice donor/acceptor (+/-2bp)		5	2			7
splice region		1	7	11		19
non coding			12	48	12	72
Total	9	11	185	160	14

Highest pathogenic variant AF is 0.00000657

Variants in EFEMP2

This is a list of pathogenic ClinVar variants found in the EFEMP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-65866515-G-C		Cutis laxa, autosomal recessive, type 1B	Benign (Jan 12, 2018)
11-65866613-G-A		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Jan 13, 2018)
11-65866636-G-A		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Jan 13, 2018)
11-65866671-T-G		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Jan 12, 2018)
11-65866736-T-C		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Jan 13, 2018)
11-65866744-C-T		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Jan 12, 2018)
11-65866752-G-GC		Cutis laxa, recessive	Uncertain significance (Jun 14, 2016)
11-65866803-C-T		Cutis laxa, autosomal recessive, type 1B	Conflicting classifications of pathogenicity (Jul 17, 2018)
11-65866898-G-A			Likely benign (Feb 01, 2018)
11-65866915-T-C		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Jan 13, 2018)
11-65866925-G-T		Cardiovascular phenotype • Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Mar 13, 2022)
11-65866927-G-A		Cardiovascular phenotype	Likely benign (Jan 18, 2020)
11-65866939-A-C		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Mar 30, 2021)
11-65866944-C-T		Cutis laxa, autosomal recessive, type 1B • Cardiovascular phenotype	Uncertain significance (Dec 11, 2023)
11-65866945-G-A		Cutis laxa, autosomal recessive, type 1B	Likely benign (Oct 15, 2023)
11-65866945-G-C		Cutis laxa, autosomal recessive, type 1B	Likely benign (Feb 19, 2021)
11-65866948-G-A		Cutis laxa, autosomal recessive, type 1B	Likely benign (Jul 20, 2022)
11-65866960-AGAGCTGGCCCG-A			Uncertain significance (Sep 19, 2017)
11-65866961-G-T		Cardiovascular phenotype	Uncertain significance (Apr 28, 2023)
11-65866967-G-A		Cutis laxa, autosomal recessive, type 1B	Uncertain significance (Apr 25, 2018)
11-65866970-C-T		Cardiovascular phenotype	Uncertain significance (Apr 11, 2022)
11-65866971-G-A		Cutis laxa, autosomal recessive, type 1B • Cardiovascular phenotype	Uncertain significance (Sep 01, 2021)
11-65866999-C-G		Cardiovascular phenotype	Uncertain significance (Mar 05, 2024)
11-65867002-C-T		Cutis laxa, autosomal recessive, type 1B	Likely benign (Aug 04, 2023)
11-65867014-C-T		Cutis laxa, autosomal recessive, type 1B	Likely benign (Feb 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EFEMP2	protein_coding	protein_coding	ENST00000307998	10	7152

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00819	0.991	125727	0	19	125746	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.976	236	282	0.836	0.0000203	2896
Missense in Polyphen		73	105.53	0.69172		1105
Synonymous	-1.70	142	118	1.20	0.00000913	856
Loss of Function	3.03	8	24.0	0.333	0.00000113	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.000326	0.000326
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Cutis laxa, autosomal recessive, 1B (ARCL1B) [MIM:614437]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. ARCL1B features include emphysema, lethal pulmonary artery occlusion, aortic aneurysm, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels. {ECO:0000269|PubMed:16685658, ECO:0000269|PubMed:17937443, ECO:0000269|PubMed:19664000}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.125
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.173
• hipred: Y
• hipred_score: 0.589
• ghis: 0.616

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.452

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Efemp2
• Phenotype: normal phenotype; 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); 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); respiratory system phenotype; skeleton phenotype; vision/eye phenotype; limbs/digits/tail phenotype; muscle 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); cellular phenotype

Gene ontology

• Biological process: elastic fiber assembly
• Cellular component: extracellular region;basement membrane;collagen-containing extracellular matrix;extracellular exosome;extracellular vesicle
• Molecular function: extracellular matrix structural constituent;calcium ion binding;protein binding