ARHGEF10L

protein-coding

Rho guanine nucleotide exchange factor 10 like, the group of Dbl family Rho GEFs

Gene summary

This gene belongs to the RhoGEF subfamily of RhoGTPases. Members of this subfamily are activated by specific guanine nucleotide exchange factors (GEFs) and are involved in signal transduction. The encoded protein shows cytosolic distribution. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2016]

MANE transcript

NM_018125.4

Inheritance

—

ClinVar variants

P:1U:213B:16

Top phenotype

Teratoma

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr1:17,539,698-17,697,874

External References & Databases

Ensembl (ENSG00000074964)

Transcript & Mutation Effects

hg38 • Region Span ~158.2 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 ARHGEF10L variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 186

not providedTotal: 12

TeratomaTotal: 1

Cerebral visual impairment and intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018125.4. 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			10 clinvar	6 clinvar	3 clinvar	19
missense		1 clinvar	195 clinvar	4 clinvar	3 clinvar	203
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	1	213	10	6	230

Highest pathogenic variant AF is 0.0000061656337

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 129 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018125.4	RefSeq	NP_060595.3	28	MANE Select
ENST00000361221.8	Ensembl	ENSP00000355060.3	28	MANE Select
NM_001011722.2	RefSeq	NP_001011722.2	27	Standard
NM_001319837.2	RefSeq	NP_001306766.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases
NRAGE signals death through JNK

Biological Process

actin cytoskeleton organization
SREBP signaling pathway
regulation of Rho protein signal transduction
positive regulation of GTPase activity
positive regulation of stress fiber assembly

Molecular Function

guanyl-nucleotide exchange factor activity
Rho guanyl-nucleotide exchange factor activity
GTPase activator activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361221
Coding exons: 28
Length: 158040
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125748
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	672	791	0.849	0.0000507	8257
Missense (PolyPhen)		152	219.74	0.69172		2178
Synonymous	-0.370	351	342	1.03	0.0000240	2583
Loss of Function	5.06	18	60.4	0.298	0.00000286	678

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for RHOA, RHOB and RHOC. {ECO:0000269|PubMed:16112081}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.569
RVIS EVS: -0.76
RVIS percentile EVS: 13.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.223

Gene Damage Prediction

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