DISC1

Chr 1

DISC1 scaffold protein

Also known as: C1orf136, SCZD9

NCBI Gene: 27185ENSG00000162946UniProt: Q9NRI5

This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtSchizophrenia 9
232
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DISC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 112 VUS of 232 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.79LOEUF
pLI 0.000
Z-score 2.42
OE 0.50 (0.33–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.41Z-score
OE missense 0.94 (0.86–1.03)
369 obs / 391.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.50 (0.33–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 14 / 27.7Missense obs/exp: 369 / 391.9Syn Z: 0.93

ClinVar Variant Classifications

232 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic4
VUS112
Likely Benign40
Benign15
Conflicting1
35
Pathogenic
4
Likely Pathogenic
112
VUS
40
Likely Benign
15
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
4
0
4
VUS
1
90
20
1
112
Likely Benign
0
19
5
16
40
Benign
0
9
2
4
15
Conflicting
—1
Total11186621207

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DISC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neurobiology of schizophrenia.
Ross CA et al.·Neuron
2006Review
Role of DISC1 in neural development and schizophrenia.
Mackie S et al.·Curr Opin Neurobiol
2007Review
Neuroglial Advances: New Roles for Established Players.
Verkhratsky A et al.·J Neurochem
2025Review
Pathological oligodendrocyte precursor cells revealed in human schizophrenic brains and trigger schizophrenia-like behaviors and synaptic defects in genetic animal model.
Yu G et al.·Mol Psychiatry
2022Functional
Impact of COMT, PRODH and DISC1 Genetic Variants on Cognitive Performance of Patients with Schizophrenia.
Fricke-Galindo I et al.·Arch Med Res
2022Cohort
The genetic deconstruction of psychosis.
Owen MJ et al.·Schizophr Bull
2007Review
Disrupted in schizophrenia 1 (DISC1) is a constituent of the mammalian mitochondrial contact site and cristae organizing system (MICOS) complex, and is essential for oxidative phosphorylation.
Piñero-Martos E et al.·Hum Mol Genet
2016
Dendritic spine pathology in schizophrenia.
Glausier JR et al.·Neuroscience
2013Review
The DISC locus in psychiatric illness.
Chubb JE et al.·Mol Psychiatry
2008Review
Evaluating historical candidate genes for schizophrenia.
Farrell MS et al.·Mol Psychiatry
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cytomegalovirus (CMV)-encoded immediate early 1 (IE1) protein perturbs neural progenitor proliferation via interfering with host PML-DISC1 interaction.
Saito A et al.·J Biol Chem
2026
Pharmacological rescue of social deficits in rats featuring Disrupted-in-Schizophrenia-1 (DISC1) protein aggregation.
Dören J et al.·Schizophrenia (Heidelb)
2026🔓 Open Access
GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities in Mecp2 and Disc1 transgenic mice.
Ge Y et al.·Sci Adv
2026🔓 Open Access
The Mechanisms by Which RhoA Activity and Associated Synaptic Effects Are Controlled by the DISC1 Scaffolding-Like Protein.
Bjornson KJ et al.·Biol Psychiatry
2025Functional
DISC1 Protects Against Zika Virus Infection and Long-Term Neurological Damage Through AMPK-mTOR-Mediated Autophagy.
Zhang S et al.·Nat Commun
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools