GTPBP1

protein-coding

GTP binding protein 1

Gene summary

This gene is upregulated by interferon-gamma and encodes a protein that is a member of the AGP11/GTPBP1 family of GTP-binding proteins. A structurally similar protein has been found in mouse, where disruption of the gene for that protein had no observable phenotype. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004286.5

Inheritance

ClinVar variants

P:4U:75B:3

Top phenotype

Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr22:38,705,742-38,738,299

External References & Databases

Ensembl (ENSG00000100226)

Transcript & Mutation Effects

hg38 • Region Span ~32.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0975745

Submitter: G2P

neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0975745

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1AR

Manifestation: Craniofacial; Dental; Dermatologic; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 38118446

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GTPBP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 63

Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1Total: 5

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004286.5. 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	2 clinvar		5
missense	1 clinvar		68 clinvar		1 clinvar	70
nonsense	2 clinvar					2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	4	0	75	2	1	82

Highest pathogenic variant AF is 6.8846913e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004286.5	RefSeq	NP_004277.2	12	MANE Select
ENST00000216044.10	Ensembl	ENSP00000216044.5	12	MANE Select
ENST00000418601.1	Ensembl	ENSP00000397891.1	2	Standard
ENST00000458073.5	Ensembl	ENSP00000388147.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

translational elongation
immune response
signal transduction
GTP metabolic process
positive regulation of mRNA catabolic process

Molecular Function

RNA binding
translation elongation factor activity
GTPase activity
GTP binding

Cellular Component

cytoplasmic exosome (RNase complex)
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216044
Coding exons: 12
Length: 32577
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125736
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.36	205	392	0.523	0.0000241	4330
Missense (PolyPhen)		45	174.25	0.25824		1775
Synonymous	1.34	136	157	0.864	0.00000956	1398
Loss of Function	4.01	4	26.1	0.153	0.00000146	299

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.00011	0.000092	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes degradation of target mRNA species. Plays a role in the regulation of circadian mRNA stability. Binds GTP and has GTPase activity (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.173

Intolerance Scores

LoFtool: 0.271
RVIS EVS: -0.78
RVIS percentile EVS: 12.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.884

Gene Damage Prediction

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