ARHGAP33

protein-coding

Rho GTPase activating protein 33, the group of Rho GTPase activating proteins

Gene summary

This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. Alternative splice variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

Previous symbols:

SNX26

MANE transcript

NM_001366178.1

Inheritance

ClinVar variants

U:184B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr19:35,774,532-35,788,822

External References & Databases

Ensembl (ENSG00000004777)

Transcript & Mutation Effects

hg38 • Region Span ~14.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGAP33 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 178

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001366178.1. 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			5 clinvar	3 clinvar	3 clinvar	11
missense			177 clinvar	5 clinvar		182
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	184	8	3	195

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001366178.1	RefSeq	NP_001353107.1	21	MANE Select
ENST00000007510.9	Ensembl	ENSP00000007510.6	21	MANE Select
NM_001172630.2	RefSeq	NP_001166101.1	17	Standard
NM_052948.4	RefSeq	NP_443180.2	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin Signaling
Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases

Biological Process

small GTPase mediated signal transduction
response to toxic substance
protein transport
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activator activity
protein binding
protein kinase binding
phosphatidylinositol binding

Cellular Component

cytoplasm
cytosol
plasma membrane
protein-containing complex
dendritic spine

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000314737
Coding exons: 21
Length: 14291
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125747
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.80	576	711	0.810	0.0000468	7016
Missense (PolyPhen)		171	193.49	0.88375		2036
Synonymous	-0.276	310	304	1.02	0.0000198	2532
Loss of Function	5.03	14	53.9	0.260	0.00000310	529

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00017	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00013	0.00013	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in several stages of intracellular trafficking. Could play an important role in the regulation of glucose transport by insulin. May act as a downstream effector of RHOQ/TC10 in the regulation of insulin-stimulated glucose transport (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.678
RVIS EVS: -1.46
RVIS percentile EVS: 3.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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