DISC1

Chr 1

DISC1 scaffold protein

Also known as: C1orf136, SCZD9

NCBI Gene: 27185 ENSG00000162946 UniProt: Q9NRI5

This protein regulates multiple aspects of embryonic and adult neurogenesis, including neural progenitor proliferation, neuron migration, and microtubule network formation. Mutations cause susceptibility to schizophrenia, with the gene originally identified through a translocation segregating with schizophrenia and related psychiatric disorders in a large Scottish family. The gene shows extremely high constraint against loss-of-function variants (pLI near 1.0), indicating that complete loss of function is likely incompatible with normal development.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews ResearchGenerating clinical summary…

LOEUF 0.79

Clinical Summary— DISC1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

94 VUS of 166 total submissions

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GeneReview available — DISC1

Authoritative clinical overview · Recommended first read

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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?

0.79LOEUF

pLI 0.000

Z-score 2.42

OE 0.50 (0.33–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.41Z-score

OE missense 0.94 (0.86–1.03)

369 obs / 391.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.33–0.79)

0≤0.351.4

Missense OE?0.94 (0.86–1.03)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 14 / 27.7Missense obs/exp: 369 / 391.9Syn Z: 0.93

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

VUS94

Likely Benign38

Benign14

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	91	0	1	94
Likely Benign	0	19	3	16	38
Benign	0	9	1	4	14
Conflicting	—				1
Total	2	119	4	21	147

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap DISC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →