REPS2

protein-coding

RALBP1 associated Eps domain containing 2, the group of EF-hand domain containing

Gene summary

The product of this gene is part of a protein complex that regulates the endocytosis of growth factor receptors. The encoded protein directly interacts with a GTPase activating protein that functions downstream of the small G protein Ral. Its expression can negatively affect receptor internalization and inhibit growth factor signaling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004726.3

Inheritance

ClinVar variants

U:147B:10

Top phenotype

Developmental and epileptic encephalopathy, 1

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chrX:16,946,658-17,153,272

External References & Databases

Ensembl (ENSG00000169891)

Transcript & Mutation Effects

hg38 • Region Span ~206.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to REPS2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 8

Developmental and epileptic encephalopathy, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004726.3. 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			11 clinvar	4 clinvar	1 clinvar	16
missense			100 clinvar	5 clinvar		105
nonsense			7 clinvar			7
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			28 clinvar			28
Total	0	0	147	9	1	157

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004726.3	RefSeq	NP_004717.2	18	MANE Select
ENST00000357277.8	Ensembl	ENSP00000349824.3	18	MANE Select
NM_001080975.2	RefSeq	NP_001074444.1	18	Standard
ENST00000303843.7	Ensembl	ENSP00000306033.7	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-EGFR Signaling Pathway
Vesicle-mediated transport
Membrane Trafficking
Clathrin-mediated endocytosis
EGFR1

Biological Process

epidermal growth factor receptor signaling pathway
membrane organization
protein-containing complex assembly

Molecular Function

calcium ion binding
protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357277
Coding exons: 18
Length: 206582
Individuals with no LoFs: 125728
Homozygous LoFs: 3
Heterozygous LoFs: 4
Defined: 125735
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.31	174	230	0.757	0.0000180	4232
Missense (PolyPhen)		41	68.981	0.59436		1147
Synonymous	-0.549	94	87.5	1.07	0.00000691	1336
Loss of Function	3.45	6	24.4	0.246	0.00000179	439

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000040	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000025	0.000018	rare
South Asian	0.00016	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in growth factor signaling through its influence on the Ral signaling pathway.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.346
RVIS EVS: -0.18
RVIS percentile EVS: 40.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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