GEM

protein-coding

GTP binding protein overexpressed in skeletal muscle, the group of RGK type GTPase family

Gene summary

The protein encoded by this gene belongs to the RAD/GEM family of GTP-binding proteins. It is associated with the inner face of the plasma membrane and could play a role as a regulatory protein in receptor-mediated signal transduction. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005261.4

Inheritance

—

ClinVar variants

U:39B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr8:94,249,253-94,262,350

External References & Databases

Ensembl (ENSG00000164949)

Transcript & Mutation Effects

hg38 • Region Span ~13.1 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 GEM variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 36

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005261.4. 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			2 clinvar			2
missense			37 clinvar	2 clinvar	2 clinvar	41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	39	2	2	43

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005261.4	RefSeq	NP_005252.1	4	MANE Select
ENST00000297596.3	Ensembl	ENSP00000297596.2	4	MANE Select
NM_181702.3	RefSeq	NP_859053.1	4	Standard
ENST00000396194.6	Ensembl	ENSP00000379497.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mitotic cell cycle
immune response
signal transduction
cell surface receptor signaling pathway
chromosome organization

Molecular Function

magnesium ion binding
GTPase activity
calcium channel regulator activity
protein binding
calmodulin binding

Cellular Component

nucleus
plasma membrane
cytoplasmic side of plasma membrane
midbody
spindle midzone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000297596
Coding exons: 4
Length: 13098
Individuals with no LoFs: 125597
Homozygous LoFs: 0
Heterozygous LoFs: 151
Defined: 125748
p: 0.000601

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.117	183	188	0.976	0.0000116	1949
Missense (PolyPhen)		78	78.608	0.99227		735
Synonymous	0.868	60	69.2	0.867	0.00000376	579
Loss of Function	0.741	14	17.3	0.808	0.00000135	129

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0027	0.0027	notable
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00077	0.00076	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Could be a regulatory protein, possibly participating in receptor-mediated signal transduction at the plasma membrane. Has guanine nucleotide-binding activity but undetectable intrinsic GTPase activity.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.844
RVIS EVS: -0.01
RVIS percentile EVS: 53.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.750

Gene Damage Prediction

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