GRIPAP1

protein-coding

GRIP1 associated protein 1

Gene summary

This gene encodes a guanine nucleotide exchange factor for the Ras family of small G proteins (RasGEF). The encoded protein interacts in a complex with glutamate receptor interacting protein 1 (GRIP1) and plays a role in the regulation of AMPA receptor function. [provided by RefSeq, Aug 2013]

MANE transcript

NM_020137.5

Inheritance

—

ClinVar variants

U:135B:8

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chrX:48,973,720-49,002,265

External References & Databases

Ensembl (ENSG00000068400)

Transcript & Mutation Effects

hg38 • Region Span ~28.5 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 GRIPAP1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 11

Neurodevelopmental disorderTotal: 1

GRIPAP1-related conditionTotal: 1

SeizureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020137.5. 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			11 clinvar	1 clinvar	2 clinvar	14
missense			87 clinvar	4 clinvar	1 clinvar	92
nonsense			9 clinvar			9
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			28 clinvar			28
Total	0	0	135	5	3	143

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 147 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020137.5	RefSeq	NP_064522.4	26	MANE Select
ENST00000376423.8	Ensembl	ENSP00000365606.5	26	MANE Select
ENST00000593475.6	Ensembl	ENSP00000469842.2	25	Standard
ENST00000593475.7	Ensembl	ENSP00000469842.2	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process
neurotransmitter receptor transport, endosome to postsynaptic membrane
regulation of neurotransmitter receptor transport, endosome to postsynaptic membrane
regulation of recycling endosome localization within postsynapse
regulation of modification of synaptic structure

Molecular Function

molecular_function
protein binding

Cellular Component

nucleoplasm
cytosol
cell junction
axon
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376441
Coding exons: 26
Length: 28542
Individuals with no LoFs: 125728
Homozygous LoFs: 1
Heterozygous LoFs: 1
Defined: 125730
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.62	204	340	0.601	0.0000297	5491
Missense (PolyPhen)		48	119.59	0.40136		1930
Synonymous	1.61	102	125	0.817	0.00000965	1554
Loss of Function	5.53	2	39.5	0.0506	0.00000283	659

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000013	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates the endosomal recycling back to the neuronal plasma membrane, possibly by connecting early and late recycling endosomal domains and promoting segregation of recycling endosomes from early endosomal membranes. Involved in the localization of recycling endosomes to dendritic spines, thereby playing a role in the maintenance of dendritic spine morphology. Required for the activity-induced AMPA receptor recycling to dendrite membranes and for long-term potentiation and synaptic plasticity (By similarity). {ECO:0000250|UniProtKB:Q9JHZ4}.;

Recessive Scores

pRec: 0.0836

Intolerance Scores

LoFtool: 0.131
RVIS EVS: -0.29
RVIS percentile EVS: 33.34

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