SCRIB

protein-coding

scribble planar cell polarity protein, the group of PDZ domain containing|Scribble complex|MicroRNA protein coding host genes

Gene summary

This gene encodes a protein that was identified as being similar to the Drosophila scribble protein. The mammalian protein is involved in tumor suppression pathways. As a scaffold protein involved in cell polarization processes, this protein binds to many other proteins. The encoded protein binds to papillomavirus E6 protein via its PDZ domain and the C-terminus of E6. Two alternatively spliced transcript variants that encode different protein isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

MANE transcript

NM_182706.5

Inheritance

ClinVar variants

P:1U:404B:93

Top phenotype

SCRIB-related disorder

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr8:143,790,920-143,815,773

External References & Databases

Ensembl (ENSG00000180900)

UniProt (C0HLS1, Q14160)

Transcript & Mutation Effects

hg38 • Region Span ~24.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SCRIB variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 426

SCRIB-related disorderTotal: 49

not providedTotal: 33

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

MicrocephalyTotal: 1

Neural tube defectTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182706.5. 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			8 clinvar	62 clinvar	8 clinvar	78
missense			366 clinvar	17 clinvar	6 clinvar	389
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)			22 clinvar			22
Total	0	1	404	79	14	498

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182706.5	RefSeq	NP_874365.3	37	MANE Select
ENST00000356994.7	Ensembl	ENSP00000349486.2	37	MANE Select
NM_015356.5	RefSeq	NP_056171.3	36	Standard
ENST00000320476.7	Ensembl	ENSP00000322938.3	36	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
scrib	Danio rerio	Structure: neuroepithelial cell Quality: direction abnormal

Gene / Model

Organism

Observed Phenotype

scrib

Danio rerio

Structure: neuroepithelial cell

Quality: direction

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
Viral carcinogenesis - Homo sapiens (human)
Human papillomavirus infection - Homo sapiens (human)
Human Thyroid Stimulating Hormone (TSH) signaling pathway

Biological Process

neural tube closure
positive regulation of receptor recycling
cell population proliferation
synaptic vesicle targeting
cell migration

Molecular Function

protein binding
ionotropic glutamate receptor binding
cadherin binding

Cellular Component

nucleoplasm
plasma membrane
cell-cell junction
cell-cell adherens junction
ionotropic glutamate receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356994
Coding exons: 37
Length: 24460
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125746
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.381	982	1.02e+3	0.966	0.0000715	10262
Missense (PolyPhen)		402	496.94	0.80896		5047
Synonymous	-6.03	630	465	1.36	0.0000348	3599
Loss of Function	6.21	14	70.2	0.200	0.00000333	834

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000094	0.000092	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Scaffold protein involved in different aspects of polarized cells differentiation regulating epithelial and neuronal morphogenesis. Most probably functions in the establishment of apico-basal cell polarity. May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium. May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling. May play a role in exocytosis and in the targeting synaptic vesicles to synapses. Functions as an activator of Rac GTPase activity. {ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:15775968, ECO:0000269|PubMed:16344308, ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750}.;
Disease: DISEASE: Neural tube defects (NTD) [MIM:182940]: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components. {ECO:0000269|PubMed:22095531}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.135

Intolerance Scores

RVIS EVS: -2.44
RVIS percentile EVS: 1.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.736

Gene Damage Prediction

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