GMIP

protein-coding

GEM interacting protein, the group of AH/BAR family Rho GTPase activating proteins

Gene summary

This gene encodes a member of the ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. The encoded protein interacts with the Ras-related protein Gem through its N-terminal domain. Separately, it interacts with RhoA through a RhoGAP domain, and stimulates RhoA-dependent GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MANE transcript

NM_016573.4

Inheritance

—

ClinVar variants

U:133B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr19:19,629,476-19,643,657

External References & Databases

Ensembl (ENSG00000089639)

Transcript & Mutation Effects

hg38 • Region Span ~14.2 kb

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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 GMIP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 127

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016573.4. 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	3 clinvar		6
missense			124 clinvar	5 clinvar		129
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	133	8	0	141

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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_016573.4	RefSeq	NP_057657.2	21	MANE Select
ENST00000203556.9	Ensembl	ENSP00000203556.3	21	MANE Select
NM_001288998.2	RefSeq	NP_001275927.1	20	Standard
NM_001288999.2	RefSeq	NP_001275928.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases

Biological Process

negative regulation of GTPase activity
intracellular signal transduction
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activator activity
protein binding
metal ion binding

Cellular Component

nucleoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000203556
Coding exons: 21
Length: 14192
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.48	434	606	0.716	0.0000407	6143
Missense (PolyPhen)		128	209.88	0.60987		2009
Synonymous	1.67	233	268	0.870	0.0000191	2055
Loss of Function	3.16	24	47.5	0.505	0.00000254	506

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000097	0.000092	rare
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.000066	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Stimulates, in vitro and in vivo, the GTPase activity of RhoA. {ECO:0000269|PubMed:12093360}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.604
RVIS EVS: 0.32
RVIS percentile EVS: 72.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.736

Gene Damage Prediction

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