EFEMP1

EGF containing fibulin extracellular matrix protein 1, the group of Fibulins

Basic information

Region (hg38): 2:55865966-55924139

Previous symbols: [ "DHRD", "FBNL" ]

Links

ENSG00000115380 ∙ NCBI:2202 ∙ OMIM:601548 ∙ HGNC:3218 ∙ Uniprot:Q12805 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Doyne honeycomb retinal dystrophy (Strong), mode of inheritance: AD
• Doyne honeycomb retinal dystrophy (Limited), mode of inheritance: AR
• Doyne honeycomb retinal dystrophy (Supportive), mode of inheritance: AD
• Doyne honeycomb retinal dystrophy (Definitive), mode of inheritance: AD
• Doyne honeycomb retinal dystrophy (Definitive), mode of inheritance: AD
• Doyne honeycomb retinal dystrophy (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Doyne honeycomb degeneration of retina	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	10369267; 11384588; 11389162; 11825812; 12431256; 17666404; 22581936; 23036572
Photodynamic therapy may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EFEMP1 gene.

• not provided (270 variants)
• Doyne honeycomb retinal dystrophy (65 variants)
• Inborn genetic diseases (8 variants)
• Retinal dystrophy (6 variants)
• not specified (4 variants)
• 14 conditions (2 variants)
• Recessive Marfanoid Syndrome with Severe Herniation (1 variants)
• Night blindness;Retinal pigment epithelial atrophy;Optic disc drusen;Macular dystrophy;Blindness (1 variants)
• Glaucoma of childhood (1 variants)
• EFEMP1-related condition (1 variants)
• Malattia leventinese (1 variants)
• Cutis laxa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EFEMP1 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	53	6	63
missense		2	119	2	1	124
nonsense	2		4			6
start loss						0
frameshift	1	1	2			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			6	6	1	13
non coding			10	38	47	95
Total	3	3	140	93	54

Highest pathogenic variant AF is 0.00000658

Variants in EFEMP1

This is a list of pathogenic ClinVar variants found in the EFEMP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-55865985-T-G		Doyne honeycomb retinal dystrophy	Uncertain significance (Jan 13, 2018)
2-55866010-C-T		Doyne honeycomb retinal dystrophy	Benign (Jan 12, 2018)
2-55866047-G-A		Doyne honeycomb retinal dystrophy	Benign (Jan 12, 2018)
2-55866069-G-C		Doyne honeycomb retinal dystrophy	Benign (Jan 12, 2018)
2-55866111-G-T		Doyne honeycomb retinal dystrophy	Benign (Jan 13, 2018)
2-55866127-A-G		Doyne honeycomb retinal dystrophy	Uncertain significance (Jan 13, 2018)
2-55866273-G-A		Doyne honeycomb retinal dystrophy	Benign (Jan 12, 2018)
2-55866378-A-G		Doyne honeycomb retinal dystrophy	Benign (Jan 13, 2018)
2-55866386-A-G		Doyne honeycomb retinal dystrophy	Benign (Jan 12, 2018)
2-55866405-G-A		Doyne honeycomb retinal dystrophy	Benign (Jan 13, 2018)
2-55866424-G-A		Doyne honeycomb retinal dystrophy	Benign (Jan 13, 2018)
2-55866566-G-A		Doyne honeycomb retinal dystrophy	Benign (Jan 12, 2018)
2-55866724-T-A		Doyne honeycomb retinal dystrophy	Uncertain significance (Jan 13, 2018)
2-55866825-T-G		Doyne honeycomb retinal dystrophy	Benign (Jan 12, 2018)
2-55866891-C-G		Doyne honeycomb retinal dystrophy	Uncertain significance (Jan 13, 2018)
2-55866905-T-C		Doyne honeycomb retinal dystrophy	Benign (Jan 13, 2018)
2-55866921-C-T		Doyne honeycomb retinal dystrophy	Uncertain significance (Jan 12, 2018)
2-55866927-A-T		Doyne honeycomb retinal dystrophy	Uncertain significance (Jan 12, 2018)
2-55867066-GA-G		not specified • Doyne honeycomb retinal dystrophy	Benign/Likely benign (Nov 11, 2018)
2-55867073-C-A			Uncertain significance (Oct 22, 2022)
2-55867075-A-G		Glaucoma of childhood • Glaucoma 1, open angle, H	Pathogenic (Jun 21, 2023)
2-55867076-A-G			Likely benign (Jul 25, 2022)
2-55867085-T-C			Likely benign (Jun 13, 2023)
2-55867105-A-G			Likely benign (Sep 13, 2022)
2-55867114-C-A			Uncertain significance (Jul 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EFEMP1	protein_coding	protein_coding	ENST00000394555	10	58173

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000850	125417	0	1	125418	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.82	192	277	0.692	0.0000161	3241
Missense in Polyphen		51	99.814	0.51095		1148
Synonymous	-0.829	112	101	1.10	0.00000609	926
Loss of Function	4.99	1	31.0	0.0322	0.00000200	325

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways. May play a role in cell adhesion and migration. May function as a negative regulator of chondrocyte differentiation. In the olfactory epithelium, it may regulate glial cell migration, differentiation and the ability of glial cells to support neuronal neurite outgrowth. {ECO:0000269|PubMed:19804359, ECO:0000269|PubMed:19887559, ECO:0000269|PubMed:20005202}.
• Pathway: Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation (Consensus)

Recessive Scores

• pRec: 0.235

Intolerance Scores

• loftool: 0.0142
• rvis_EVS: -0.76
• rvis_percentile_EVS: 13.45

Haploinsufficiency Scores

• pHI: 0.175
• hipred: Y
• hipred_score: 0.765
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.774

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Efemp1
• 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; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; renal/urinary system phenotype; skeleton phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive system 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); pigmentation phenotype; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;epidermal growth factor receptor signaling pathway;visual perception;regulation of signaling receptor activity;peptidyl-tyrosine phosphorylation;negative regulation of chondrocyte differentiation;camera-type eye development;embryonic eye morphogenesis;post-embryonic eye morphogenesis
• Cellular component: extracellular region;extracellular space;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: epidermal growth factor-activated receptor activity;epidermal growth factor receptor binding;extracellular matrix structural constituent;calcium ion binding;protein binding;growth factor activity