EFR3A

protein-coding

EFR3 homolog A, the group of Armadillo like helical domain containing

Gene summary

The protein encoded by this gene is part of a complex that plays a role in maintaining an active pool of phosphatidylinositol 4-kinase (PI4K) at the plasma membrane. This protein is thought to be a peripheral membrane protein that associates with the plasma membrane through palmitoylation. Studies indicate that this gene product plays a role in controlling G protein-coupled receptor (GPCR) activity by affecting receptor phosphorylation. Whole exome sequencing studies have implicated mutations in this gene with autism spectrum disorders. [provided by RefSeq, Apr 2016]

MANE transcript

NM_015137.6

Inheritance

—

ClinVar variants

U:120B:21

Top phenotype

EFR3A-related disorder

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr8:131,904,093-132,013,642

External References & Databases

Ensembl (ENSG00000132294)

Transcript & Mutation Effects

hg38 • Region Span ~109.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EFR3A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 105

EFR3A-related disorderTotal: 28

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015137.6. 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			1 clinvar	9 clinvar	1 clinvar	11
missense			108 clinvar	7 clinvar	4 clinvar	119
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	120	16	5	141

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015137.6	RefSeq	NP_055952.2	23	MANE Select
ENST00000254624.10	Ensembl	ENSP00000254624.5	23	MANE Select
NM_001323553.2	RefSeq	NP_001310482.1	21	Standard
NM_001323554.2	RefSeq	NP_001310483.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

phosphatidylinositol phosphorylation
protein localization to plasma membrane

Cellular Component

cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254624
Coding exons: 23
Length: 109555
Individuals with no LoFs: 125542
Homozygous LoFs: 0
Heterozygous LoFs: 51
Defined: 125593
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.796	376	422	0.891	0.0000221	5366
Missense (PolyPhen)		84	121.19	0.69312		1510
Synonymous	-0.169	142	139	1.02	0.00000713	1535
Loss of Function	2.78	24	43.9	0.547	0.00000255	537

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00025	0.00022	rare
South Asian	0.00014	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:25608530, PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, EFR3A probably acts as the membrane-anchoring component (PubMed:23229899). Also involved in responsiveness to G-protein-coupled receptors; it is however unclear whether this role is direct or indirect (PubMed:25380825). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:25608530, ECO:0000305}.;
Disease: DISEASE: Note=Genetic variations in EFR3A may be associated with susceptibility to autism. {ECO:0000305|PubMed:24860643}.;

Recessive Scores

pRec: 0.0879

Intolerance Scores

LoFtool: 0.923
RVIS EVS: -0.31
RVIS percentile EVS: 32.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.218

Gene Damage Prediction

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