DISC1

DISC1 scaffold protein

Basic information

Region (hg38): 1:231626789-232041272

Links

ENSG00000162946 ∙ NCBI:27185 ∙ OMIM:605210 ∙ HGNC:2888 ∙ Uniprot:Q9NRI5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DISC1 gene.

• not provided (43 variants)
• Inborn genetic diseases (31 variants)
• DISC1-related condition (5 variants)
• not specified (2 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DISC1 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			1	7	3	11
missense			34	7	6	47
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	37	14	9

Variants in DISC1

This is a list of pathogenic ClinVar variants found in the DISC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-231626905-C-G		DISC1-related disorder	Likely benign (Jan 12, 2021)
1-231626909-C-T		DISC1-related disorder	Likely benign (Jan 04, 2021)
1-231626921-G-A			not provided (-)
1-231626938-G-A		DISC1-related disorder	Likely benign (Dec 28, 2023)
1-231632793-A-T		-	no classification for the single variant (-)
1-231693867-C-T		not specified	Uncertain significance (May 04, 2022)
1-231693919-T-G		not specified	Uncertain significance (Apr 25, 2022)
1-231693921-G-A		not specified	Uncertain significance (Jun 06, 2023)
1-231693954-C-T		DISC1-related disorder	Likely benign (Feb 24, 2024)
1-231693969-G-T		DISC1-related disorder	Benign (Jul 29, 2019)
1-231693978-G-A		not specified	Uncertain significance (Nov 10, 2022)
1-231694087-C-T		not specified	Uncertain significance (Dec 06, 2022)
1-231694098-A-T			not provided (-)
1-231694100-C-A		DISC1-related disorder	Likely benign (Oct 20, 2023)
1-231694105-C-T		DISC1-related disorder	Benign (Jun 18, 2019)
1-231694137-A-G		not specified	Uncertain significance (Jan 19, 2022)
1-231694162-C-T		not specified	Likely benign (Aug 12, 2021)
1-231694215-T-C		not specified	Uncertain significance (Sep 17, 2021)
1-231694230-G-A			not provided (-)
1-231694237-G-T		DISC1-related disorder	Likely benign (Feb 27, 2024)
1-231694266-C-T		DISC1-related disorder	Benign (Aug 16, 2022)
1-231694269-G-A		not specified	Uncertain significance (May 17, 2023)
1-231694313-C-T		DISC1-related disorder	Benign/Likely benign (Dec 28, 2023)
1-231694318-G-A		DISC1-related disorder	Uncertain significance (Nov 21, 2022)
1-231694371-G-GC			Uncertain significance (Mar 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DISC1	protein_coding	protein_coding	ENST00000366633	10	414458

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000168	0.993	125715	0	31	125746	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.410	369	392	0.942	0.0000228	4841
Missense in Polyphen		90	106.17	0.84766		1435
Synonymous	0.932	148	163	0.907	0.0000100	1560
Loss of Function	2.42	14	27.7	0.505	0.00000138	332

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000608	0.000605
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000805	0.0000791
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the regulation of multiple aspects of embryonic and adult neurogenesis. Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus. Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance. Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation. Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A. Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development. Plays a role, together with PCNT, in the microtubule network formation. {ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:19303846, ECO:0000269|PubMed:19502360}.
• Disease: DISEASE: Note=A chromosomal aberration involving DISC1 segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Translocation t(1;11)(q42.1;q14.3). The truncated DISC1 protein produced by this translocation is unable to interact with ATF4, ATF5 and NDEL1.; DISEASE: Schizophrenia 9 (SCZD9) [MIM:604906]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. {ECO:0000269|PubMed:11468279, ECO:0000269|PubMed:14532331, ECO:0000269|PubMed:15386212, ECO:0000269|PubMed:15939883}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.269

Intolerance Scores

• loftool: 0.823
• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.46

Haploinsufficiency Scores

• pHI: 0.0891
• hipred: Y
• hipred_score: 0.542
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.399

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Disc1
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: disc1
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: increased branchiness

Gene ontology

• Biological process: microtubule cytoskeleton organization;neuron migration;positive regulation of neuroblast proliferation;Wnt signaling pathway;positive regulation of Wnt signaling pathway;negative regulation of protein binding;non-motile cilium assembly
• Cellular component: mitochondrion;centrosome;microtubule;postsynaptic density;cell junction;intermediate filament cytoskeleton;postsynaptic membrane;ciliary base
• Molecular function: protein binding