RHPN2

protein-coding

rhophilin Rho GTPase binding protein 2, the group of PDZ domain containing

Gene summary

This gene encodes a member of the rhophilin family of Ras-homologous (Rho)-GTPase binding proteins. The encoded protein binds both GTP- and GDP-bound RhoA and GTP-bound RhoB and may be involved in the organization of the actin cytoskeleton. [provided by RefSeq, Apr 2009]

MANE transcript

NM_033103.5

Inheritance

—

ClinVar variants

U:96B:11

Top phenotype

Infantile epilepsy syndrome

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr19:32,978,592-33,064,888

External References & Databases

Ensembl (ENSG00000131941)

Transcript & Mutation Effects

hg38 • Region Span ~86.3 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 RHPN2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 92

not providedTotal: 8

Infantile epilepsy syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033103.5. 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			6 clinvar	1 clinvar		7
missense			87 clinvar	7 clinvar	3 clinvar	97
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	96	8	3	107

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033103.5	RefSeq	NP_149094.3	15	MANE Select
ENST00000254260.8	Ensembl	ENSP00000254260.2	15	MANE Select
ENST00000588388.5	Ensembl	ENSP00000465898.1	4	Standard
ENST00000859930.1	Ensembl	ENSP00000529989.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

G13 Signaling Pathway
Signal Transduction
RHO GTPases Activate Rhotekin and Rhophilins
RHO GTPase Effectors
Signaling by Rho GTPases

Biological Process

signal transduction

Cellular Component

cytosol
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254260
Coding exons: 15
Length: 86296
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.315	369	386	0.955	0.0000255	4458
Missense (PolyPhen)		97	119.31	0.81302		1487
Synonymous	1.27	145	166	0.875	0.0000120	1335
Loss of Function	2.65	17	33.6	0.506	0.00000170	395

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00038	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds specifically to GTP-Rho. May function in a Rho pathway to limit stress fiber formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity. {ECO:0000269|PubMed:12221077}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.744
RVIS EVS: 0
RVIS percentile EVS: 54.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High