SCRIB

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

Basic information

Region (hg38): 8:143790919-143815773

Links

ENSG00000180900 ∙ NCBI:23513 ∙ OMIM:607733 ∙ HGNC:30377 ∙ Uniprot:C0HLS1, Q14160 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SCRIB 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				24	12	36
missense			132	9	8	149
nonsense		1				1
start loss						0
frameshift			1			1
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region			1	13		14
non coding			1	7	1	9
Total	0	1	134	41	21

Variants in SCRIB

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

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

Position	Type	Phenotype	Significance	ClinVar
8-143791171-G-A		not specified	Uncertain significance (Jan 31, 2024)
8-143791191-C-T		not specified	Uncertain significance (Jan 26, 2023)
8-143791209-C-A		not specified	Uncertain significance (Jan 06, 2023)
8-143791210-G-A		not specified	Uncertain significance (May 15, 2024)
8-143791252-C-T		not specified	Uncertain significance (Oct 14, 2021)
8-143791412-G-A		not specified	Uncertain significance (Dec 20, 2023)
8-143791436-G-A			Likely benign (Mar 30, 2018)
8-143791657-GC-G			Likely benign (Nov 14, 2017)
8-143791676-T-C		not specified	Uncertain significance (Oct 04, 2022)
8-143791704-C-A		not specified	Uncertain significance (Jan 04, 2024)
8-143791721-A-C		not specified	Uncertain significance (Oct 29, 2021)
8-143791725-T-G		not specified	Uncertain significance (Jul 31, 2023)
8-143791729-T-C			Likely benign (May 21, 2018)
8-143791880-C-T		not specified	Uncertain significance (Jun 07, 2024)
8-143791886-G-A		not specified	Uncertain significance (Feb 28, 2023)
8-143791908-C-T		SCRIB-related disorder	Benign (Oct 21, 2019)
8-143792000-G-C		not specified	Uncertain significance (Nov 06, 2023)
8-143792008-G-A		not specified	Uncertain significance (Dec 09, 2023)
8-143792020-G-C		not specified	Uncertain significance (Oct 30, 2023)
8-143792026-G-T		not specified	Uncertain significance (Jun 13, 2023)
8-143792060-G-A		not specified	Uncertain significance (Aug 04, 2023)
8-143792102-C-T		not specified	Uncertain significance (Jun 16, 2023)
8-143792137-C-T		SCRIB-related disorder	Likely benign (Jan 11, 2020)
8-143792212-G-A		SCRIB-related disorder	Likely benign (May 04, 2019)
8-143792269-C-T		not specified	Uncertain significance (Mar 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SCRIB	protein_coding	protein_coding	ENST00000356994	37	24460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.929	0.0707	125724	0	22	125746	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.381	982	1.02e+3	0.966	0.0000715	10262
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000202	0.000183
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000942	0.0000924
European (Non-Finnish)	0.000113	0.000105
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000328	0.0000327
Other	0.000163	0.000163

dbNSFP

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.
• Pathway: 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;Signaling by WNT;Signal Transduction;Asymmetric localization of PCP proteins;PCP/CE pathway;EGFR1;Beta-catenin independent WNT signaling;TSH (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• rvis_EVS: -2.44
• rvis_percentile_EVS: 1.03

Haploinsufficiency Scores

• pHI: 0.424
• hipred: Y
• hipred_score: 0.756
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.736

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Scrib
• Phenotype: embryo phenotype; respiratory system 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); reproductive system phenotype; 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); neoplasm; pigmentation phenotype; limbs/digits/tail 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); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; vision/eye phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: scrib
• Affected structure: neuroepithelial cell
• Phenotype tag: abnormal
• Phenotype quality: direction

Gene ontology

• Biological process: neural tube closure;positive regulation of receptor recycling;cell population proliferation;synaptic vesicle targeting;cell migration;cochlear nucleus development;establishment of apical/basal cell polarity;suppression by virus of host type I interferon-mediated signaling pathway;suppression by virus of host STAT1 activity;suppression by virus of host STAT2 activity;wound healing;positive regulation of apoptotic process;receptor clustering;astrocyte cell migration;establishment or maintenance of epithelial cell apical/basal polarity;negative regulation of mitotic cell cycle;synaptic vesicle endocytosis;positive chemotaxis;auditory receptor cell stereocilium organization;apoptotic process involved in morphogenesis;mammary gland duct morphogenesis;protein localization to adherens junction;activation of GTPase activity;receptor localization to synapse;cell-cell adhesion;neurotransmitter receptor transport, endosome to postsynaptic membrane;neurotransmitter receptor transport postsynaptic membrane to endosome;regulation of postsynaptic neurotransmitter receptor internalization
• Cellular component: nucleoplasm;plasma membrane;cell-cell junction;cell-cell adherens junction;ionotropic glutamate receptor complex;postsynaptic density;basolateral plasma membrane;lamellipodium;cell junction;cell leading edge;Scrib-APC-beta-catenin complex;myelin sheath abaxonal region;presynaptic membrane;cell-cell contact zone;synapse;postsynaptic membrane;extracellular exosome;glutamatergic synapse;extrinsic component of postsynaptic density membrane
• Molecular function: protein binding;ionotropic glutamate receptor binding;cadherin binding