ARHGAP39

protein-coding

Rho GTPase activating protein 39, the group of Rho GTPase activating proteins

Gene summary

Predicted to enable GTPase activator activity. Involved in postsynapse organization. Is active in glutamatergic synapse. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_025251.3

Inheritance

ClinVar variants

U:199B:14

Top phenotype

Pontoneocerebellar hypoplasia

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr8:144,529,179-144,685,846

External References & Databases

Ensembl (ENSG00000147799)

Transcript & Mutation Effects

hg38 • Region Span ~156.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

central nervous system malformationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020022

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGAP39 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 197

not providedTotal: 5

Pontoneocerebellar hypoplasiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025251.3. 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			4 clinvar	3 clinvar	2 clinvar	9
missense			193 clinvar	9 clinvar		202
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	199	12	2	213

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025251.3	RefSeq	NP_079527.1	11	MANE Select
ENST00000377307.7	Ensembl	ENSP00000366522.2	11	MANE Select
NM_001308207.1	RefSeq	NP_001295136.1	10	Standard
NM_001308208.2	RefSeq	NP_001295137.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
Signal Transduction
Rho GTPase cycle
Inactivation of CDC42 and RAC1
Signaling by Rho GTPases

Biological Process

signal transduction
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction
postsynapse organization

Molecular Function

GTPase activator activity

Cellular Component

nucleus
cytoplasm
cytosol
cytoskeleton
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377307
Coding exons: 11
Length: 156632
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 125741
p: 0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.52	534	725	0.736	0.0000494	7132
Missense (PolyPhen)		147	256.22	0.57372		2490
Synonymous	-0.956	360	338	1.07	0.0000259	2223
Loss of Function	4.51	13	46.0	0.282	0.00000213	494

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.0010	0.0010	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00053	0.00052	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

RVIS EVS: -1.39
RVIS percentile EVS: 4.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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