GIPC1

protein-coding

GIPC PDZ domain containing family member 1, the group of PDZ domain containing

Gene summary

GIPC1 is a scaffolding protein that regulates cell surface receptor expression and trafficking (Lee et al., 2008 [PubMed 18775991]).[supplied by OMIM, Apr 2009]

Previous symbols:

C19orf3
RGS19IP1

MANE transcript

NM_005716.4

Inheritance

ClinVar variants

U:61B:5

Top phenotype

Oculopharyngodistal myopathy 2

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr19:14,477,760-14,496,149

External References & Databases

Ensembl (ENSG00000123159)

Transcript & Mutation Effects

hg38 • Region Span ~18.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

oculopharyngodistal myopathy 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030134

Submitter: Labcorp Genetics (formerly Invitae)

oculopharyngodistal myopathy 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0030134

Submitter: PanelApp Australia

oculopharyngodistal myopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0025193

Submitter: Orphanet

Clinical Genomic Database (CGD)

Oculopharyngodistal myopathy 2AD

Manifestation: Musculoskeletal

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: 32413282

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GIPC1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 5

GIPC1-related conditionTotal: 2

Oculopharyngodistal myopathy 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005716.4. 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			1 clinvar	3 clinvar		4
missense			58 clinvar	2 clinvar		60
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	61	5	0	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005716.4	RefSeq	NP_005707.1	6	MANE Select
ENST00000393033.9	Ensembl	ENSP00000376753.3	6	MANE Select
NM_202468.3	RefSeq	NP_974197.1	6	Standard
NM_202469.3	RefSeq	NP_974198.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
gipc1	Danio rerio	Structure: vascular lymphangioblast Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

gipc1

Danio rerio

Structure: vascular lymphangioblast

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

VEGFA-VEGFR2 Signaling Pathway
Neurotrophic factor-mediated Trk receptor signaling
Syndecan-4-mediated signaling events

Biological Process

protein targeting
G protein-coupled receptor signaling pathway
chemical synaptic transmission
glutamate secretion
positive regulation of transforming growth factor beta receptor signaling pathway

Molecular Function

actin binding
signaling receptor binding
protein binding
myosin binding
PDZ domain binding

Cellular Component

cytoplasm
cytosol
brush border
cell cortex
synaptic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393033
Coding exons: 6
Length: 18373
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125745
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.542	196	219	0.897	0.0000149	2109
Missense (PolyPhen)		65	76.978	0.8444		852
Synonymous	-1.64	120	99.2	1.21	0.00000724	716
Loss of Function	1.67	5	11.0	0.456	5.67e-7	131

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000065	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in G protein-linked signaling.;

Recessive Scores

pRec: 0.199

Intolerance Scores

LoFtool: 0.0983
RVIS EVS: 0.11
RVIS percentile EVS: 61.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.765

Gene Damage Prediction

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