ARHGEF39

protein-coding

Rho guanine nucleotide exchange factor 39, the group of Dbl family Rho GEFs

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Involved in positive regulation of cell migration. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C9orf100

MANE transcript

NM_032818.3

Inheritance

—

ClinVar variants

U:60B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr9:35,658,875-35,675,866

External References & Databases

Ensembl (ENSG00000137135)

Transcript & Mutation Effects

hg38 • Region Span ~17.0 kb

Loading mutation effect viewer...

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 ARHGEF39 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 58

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032818.3. 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			2 clinvar			2
missense			58 clinvar	3 clinvar		61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	60	3	0	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032818.3	RefSeq	NP_116207.2	9	MANE Select
ENST00000378387.4	Ensembl	ENSP00000367638.3	9	MANE Select
ENST00000475323.5	Ensembl	ENSP00000436519.1	6	Standard
ENST00000490638.5	Ensembl	ENSP00000436756.1	9	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

positive regulation of cell migration
regulation of Rho protein signal transduction

Molecular Function

Rho guanyl-nucleotide exchange factor activity
protein binding

Cellular Component

plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378387
Coding exons: 9
Length: 16992
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 62
Defined: 125748
p: 0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.569	173	195	0.885	0.0000116	2118
Missense (PolyPhen)		62	75.689	0.81914		871
Synonymous	0.698	66	73.6	0.897	0.00000344	696
Loss of Function	0.612	17	19.9	0.852	0.00000108	205

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00036	0.00035	rare
South Asian	0.00029	0.00029	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes cell proliferation. {ECO:0000269|PubMed:22327280}.;

Recessive Scores

pRec: 0.0879

Intolerance Scores

RVIS EVS: 0.86
RVIS percentile EVS: 88.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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