ARFGEF3

protein-coding

ARFGEF family member 3, the group of Protein phosphatase 1 regulatory subunits|ARFGEF family|Armadillo like helical domain containing

Gene summary

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Predicted to be located in transport vesicle membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C6orf92
KIAA1244

MANE transcript

NM_020340.5

Inheritance

ClinVar variants

U:280B:49

Top phenotype

inherited dystonia

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr6:138,161,939-138,344,663

External References & Databases

Ensembl (ENSG00000112379)

Transcript & Mutation Effects

hg38 • Region Span ~182.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inherited dystoniaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0044807

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARFGEF3 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 286

ARFGEF3-related disorderTotal: 43

not providedTotal: 23

Neurodevelopmental disorderTotal: 1

Dystonic disorderTotal: 1

Febrile seizure (within the age range of 3 months to 6 years)Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020340.5. 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			3 clinvar	18 clinvar	12 clinvar	33
missense			266 clinvar	13 clinvar	6 clinvar	285
nonsense			5 clinvar			5
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	280	31	18	329

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020340.5	RefSeq	NP_065073.3	34	MANE Select
ENST00000251691.5	Ensembl	ENSP00000251691.4	34	MANE Select
ENST00000895851.1	Ensembl	ENSP00000565910.1	35	Standard
ENST00000895851.2	Ensembl	ENSP00000565910.1	35	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of phosphatase activity
regulation of ARF protein signal transduction

Molecular Function

ARF guanyl-nucleotide exchange factor activity

Cellular Component

integral component of membrane
transport vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000251691
Coding exons: 34
Length: 182743
Individuals with no LoFs: 125564
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125593
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.50	984	1.23e+3	0.799	0.0000731	14155
Missense (PolyPhen)		310	444.44	0.69751		5096
Synonymous	1.37	486	526	0.924	0.0000356	4305
Loss of Function	7.94	12	95.9	0.125	0.00000502	1100

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00020	0.00018	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000073	0.000070	rare
South Asian	0.00030	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (By similarity). Also regulates glucagon granule production in pancreatic alpha cells (By similarity). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (PubMed:19496786). {ECO:0000250|UniProtKB:Q3UGY8, ECO:0000269|PubMed:19496786}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

RVIS EVS: -2.22
RVIS percentile EVS: 1.34

Essentials

Essential (gene trap): N