GRIP1

glutamate receptor interacting protein 1, the group of PDZ domain containing

Basic information

Region (hg38): 12:66347431-67069162

Links

ENSG00000155974 ∙ NCBI:23426 ∙ OMIM:604597 ∙ HGNC:18708 ∙ Uniprot:Q9Y3R0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Fraser syndrome (Supportive), mode of inheritance: AR
• Fraser syndrome 1 (Strong), mode of inheritance: AR
• Fraser syndrome 3 (Definitive), mode of inheritance: AR
• Fraser syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fraser syndrome 3	AR	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	Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	22510445; 30280376

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GRIP1 gene.

• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GRIP1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	255		258
missense		1	90	5	3	99
nonsense	5	1				6
start loss			2			2
frameshift	4	1				5
inframe indel						0
splice donor/acceptor (+/-2bp)		5				5
splice region			1	46		47
non coding			35	154	13	202
Total	9	8	130	414	16

Highest pathogenic variant AF is 0.0000263

Variants in GRIP1

This is a list of pathogenic ClinVar variants found in the GRIP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-66347459-T-TA		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)
12-66347467-C-CTGTT		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)
12-66347491-TTTTA-T		Fraser syndrome 1	Likely benign (Jun 14, 2016)
12-66347508-C-T		Fraser syndrome 3	Uncertain significance (Jan 13, 2018)
12-66347521-A-AATT		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)
12-66347592-ATACTT-A		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)
12-66347628-A-AAAT		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)
12-66347691-C-T		Fraser syndrome 3	Uncertain significance (Jan 13, 2018)
12-66347705-C-T		Fraser syndrome 3	Likely benign (Jan 13, 2018)
12-66347717-G-GTGA		Fraser syndrome 1	Likely benign (Jun 14, 2016)
12-66347732-T-A		Fraser syndrome 3	Uncertain significance (Jan 13, 2018)
12-66347757-A-T		Fraser syndrome 3 • GRIP1-related disorder	Uncertain significance (Jan 12, 2018)
12-66347757-AT-A		Fraser syndrome 1	Benign (Jun 14, 2016)
12-66347757-A-AT		Fraser syndrome 1	Conflicting classifications of pathogenicity (Jun 14, 2016)
12-66347757-A-ATT		GRIP1-related disorder	Likely benign (Nov 11, 2021)
12-66347803-C-A		Fraser syndrome 3	Uncertain significance (Jan 12, 2018)
12-66347870-T-C		Fraser syndrome 3	Uncertain significance (Jan 12, 2018)
12-66348000-G-A		Fraser syndrome 3	Uncertain significance (Jan 13, 2018)
12-66348089-A-T		Fraser syndrome 3	Uncertain significance (Jan 13, 2018)
12-66348104-A-G		Fraser syndrome 3	Uncertain significance (Jan 12, 2018)
12-66348187-C-G		Fraser syndrome 3	Uncertain significance (Jan 12, 2018)
12-66348198-A-C		Fraser syndrome 3	Uncertain significance (Jan 12, 2018)
12-66348261-GATAAT-G		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)
12-66348261-G-GATA		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)
12-66348280-A-ATGTT		Fraser syndrome 1	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GRIP1	protein_coding	protein_coding	ENST00000398016	24	456756

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.508	0.492	124755	0	42	124797	0.000168

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.58	478	586	0.816	0.0000334	7006
Missense in Polyphen		104	179.21	0.58032		2096
Synonymous	-0.500	238	228	1.04	0.0000138	2181
Loss of Function	5.34	12	54.6	0.220	0.00000314	641

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000334	0.000334
Finnish	0.000464	0.000464
European (Non-Finnish)	0.000151	0.000150
Middle Eastern	0.000334	0.000334
South Asian	0.0000980	0.0000980
Other	0.000330	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). {ECO:0000250|UniProtKB:P97879, ECO:0000269|PubMed:10197531}.
• Disease: DISEASE: Fraser syndrome 3 (FRASRS3) [MIM:617667]: A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities. {ECO:0000269|PubMed:22510445}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;carm1 and regulation of the estrogen receptor;role of erbb2 in signal transduction and oncology;Neuronal System;Trafficking of GluR2-containing AMPA receptors;Trafficking of AMPA receptors;Glutamate binding, activation of AMPA receptors and synaptic plasticity;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.276

Intolerance Scores

• loftool: 0.566
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.86

Haploinsufficiency Scores

• pHI: 0.482
• hipred: Y
• hipred_score: 0.708
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Grip1
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; embryo phenotype; renal/urinary system phenotype; vision/eye 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); limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: grip1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: viability

Gene ontology

• Biological process: dendrite development;androgen receptor signaling pathway;intracellular signal transduction;positive regulation of transcription, DNA-templated;neurotransmitter receptor transport, endosome to postsynaptic membrane;vesicle-mediated transport in synapse;positive regulation of neuron projection arborization
• Cellular component: endoplasmic reticulum;cytosol;plasma membrane;cell junction;cytoplasmic vesicle;neuron projection;membrane raft;postsynaptic membrane;glutamatergic synapse
• Molecular function: transcription coactivator activity;protein binding;beta-catenin binding;protein C-terminus binding;receptor signaling complex scaffold activity;glucocorticoid receptor binding;androgen receptor binding