GDI1

GDP dissociation inhibitor 1

Basic information

Region (hg38): X:154436913-154443467

Previous symbols: [ "MRX48", "MRX41", "GDIL" ]

Links

ENSG00000203879 ∙ NCBI:2664 ∙ OMIM:300104 ∙ HGNC:4226 ∙ Uniprot:P31150 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• intellectual disability, X-linked 41 (Limited), mode of inheritance: XL
• intellectual disability, X-linked 41 (Strong), mode of inheritance: XL
• intellectual disability, X-linked 41 (Moderate), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Moderate), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked 41	XL	General	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	Neurologic	8826463; 9106537; 9668174; 9620768; 22002931

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GDI1 gene.

• not_provided (66 variants)
• Inborn_genetic_diseases (38 variants)
• Intellectual_disability,_X-linked_41 (26 variants)
• not_specified (23 variants)
• GDI1-related_disorder (6 variants)
• Intellectual_disability (2 variants)
• Immunodeficiency_47 (1 variants)
• Non-syndromic_X-linked_intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GDI1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001493.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	26	2	30
missense	1	3	62	9		75
nonsense	2	1				3
start loss						0
frameshift	5	2				7
splice donor/acceptor (+/-2bp)		2				2
Total	8	8	64	35	2

Highest pathogenic variant AF is 0.00000273737

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GDI1	protein_coding	protein_coding	ENST00000447750	11	6549

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00529	125536	0	1	125537	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.29	70	201	0.348	0.0000180	2966
Missense in Polyphen		3	67.794	0.044252		992
Synonymous	-1.73	101	81.1	1.25	0.00000750	840
Loss of Function	3.65	0	15.6	0.00	0.00000115	271

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000722	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000722	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Promotes the dissociation of GDP-bound Rab proteins from the membrane and inhibits their activation. Promotes the dissociation of RAB1A, RAB3A, RAB5A and RAB10 from membranes. {ECO:0000269|PubMed:23815289}.
• Pathway: Integrated Breast Cancer Pathway;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Rho GTPase cycle;Signaling by Rho GTPases;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs;Signaling mediated by p38-alpha and p38-beta (Consensus)

Recessive Scores

• pRec: 0.184

Intolerance Scores

• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.15

Haploinsufficiency Scores

• pHI: 0.277
• hipred: Y
• hipred_score: 0.775
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gdi1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: signal transduction;protein transport;Rab protein signal transduction;positive regulation of GTPase activity;positive regulation of axon extension;negative regulation of axonogenesis;regulation of small GTPase mediated signal transduction;response to calcium ion;negative regulation of protein targeting to membrane
• Cellular component: cytoplasm;Golgi apparatus;cytosol;axon;midbody;protein-containing complex;neuronal cell body;myelin sheath
• Molecular function: GDP-dissociation inhibitor activity;Rab GDP-dissociation inhibitor activity;GTPase activator activity;protein binding;Rab GTPase binding