ERC2

protein-coding

ELKS/RAB6-interacting/CAST family member 2, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes a protein that belongs to the Rab3-interacting molecule (RIM)-binding protein family. Members of this protein family form part of the cytomatrix at the active zone (CAZ) complex and function as regulators of neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

MANE transcript

NM_015576.3

Inheritance

—

ClinVar variants

U:103B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr3:55,508,311-56,469,095

External References & Databases

Ensembl (ENSG00000187672)

Transcript & Mutation Effects

hg38 • Region Span ~960.8 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 ERC2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 97

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015576.3. 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		1
missense			100 clinvar			100
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	103	1	0	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015576.3	RefSeq	NP_056391.1	16	MANE Select
ENST00000288221.11	Ensembl	ENSP00000288221.6	16	MANE Select
ENST00000460849.5	Ensembl	ENSP00000417445.1	16	Standard
ENST00000492584.3	Ensembl	ENSP00000417280.3	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Exercise-induced Circadian Regulation

Biological Process

synaptic vesicle priming
maintenance of presynaptic active zone structure

Molecular Function

protein binding
structural constituent of presynaptic active zone

Cellular Component

cytoskeleton
cell junction
growth cone
presynaptic membrane
presynaptic active zone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000288221
Coding exons: 16
Length: 960056
Individuals with no LoFs: 124644
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 124661
p: 0.0000682

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.22	374	516	0.724	0.0000288	6342
Missense (PolyPhen)		128	202.52	0.63205		2584
Synonymous	-1.41	223	198	1.13	0.0000111	1752
Loss of Function	5.63	9	53.3	0.169	0.00000338	603

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000098	0.000088	rare
South Asian	0.000099	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Thought to be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. Seems to act together with BSN. May recruit liprin-alpha proteins to the CAZ.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.733
RVIS EVS: -0.33
RVIS percentile EVS: 30.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.790

Gene Damage Prediction

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