ARHGEF38

protein-coding

Rho guanine nucleotide exchange factor 38, the group of Dbl family Rho GEFs|BAR and Dbl domain containing

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001242729.2

Inheritance

ClinVar variants

U:110B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr4:105,552,620-105,708,093

External References & Databases

Ensembl (ENSG00000236699)

Transcript & Mutation Effects

hg38 • Region Span ~155.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

cleft lip/palateMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0016044

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGEF38 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001242729.2. 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 clinvar		2
missense			109 clinvar	3 clinvar		112
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	110	4	0	114

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001242729.2	RefSeq	NP_001229658.1	14	MANE Select
ENST00000420470.3	Ensembl	ENSP00000416125.2	14	MANE Select
NM_017700.2	RefSeq	NP_060170.1	4	Standard
ENST00000265154.6	Ensembl	ENSP00000265154.2	4	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

regulation of Rho protein signal transduction

Molecular Function

Rho guanyl-nucleotide exchange factor activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000420470
Coding exons: 14
Length: 155474
Individuals with no LoFs: 125264
Homozygous LoFs: 2
Heterozygous LoFs: 469
Defined: 125735
p: 0.00187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.649	338	373	0.906	0.0000186	5137
Missense (PolyPhen)		106	134.52	0.78798		1855
Synonymous	0.386	135	141	0.959	0.00000722	1398
Loss of Function	1.92	19	30.5	0.624	0.00000136	479

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.0024	0.0023	notable
Ashkenazi Jewish	0.024	0.023	notable
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0011	0.0011	notable
South Asian	0.00042	0.00039	rare
Other	0.0037	0.0036	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a guanine-nucleotide releasing factor. {ECO:0000250}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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