CSMD2

Chr 1

CUB and Sushi multiple domains 2

Also known as: dJ1007G16.1, dJ1007G16.2, dJ947L8.1

NCBI Gene: 114784 ENSG00000121904 UniProt: Q7Z408 OMIM: 608398

CSMD2 encodes a protein involved in controlling the complement cascade of the immune system. Mutations in this gene have been associated with schizophrenia, though the inheritance pattern and specific neurological phenotypes in pediatric patients remain to be fully characterized. The gene may also function as a tumor suppressor in colorectal cancer.

OMIM ResearchSummary from RefSeq

The protein encoded by this gene is thought to be involved in the control of complement cascade of the immune system. Defects in this gene have been associated with schizophrenia. This gene may act as a tumor suppressor for colorectal cancer. [provided by RefSeq, Jan 2020]

OMIM ResearchGenerating clinical summary…

Multiplemechanism

Clinical Summary— CSMD2

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ClinVar Variants

491 VUS of 564 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

This gene — mechanism propensity

0.6454th %ile

GOF

0.6639th %ile

LOF

0.3939th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

564 submitted variants in ClinVar

ClinVar

Classification Summary

VUS491

Likely Benign31

Benign1

491

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	2	489	0	491
Likely Benign	0	14	17	31
Benign	0	0	1	1
Total	2	503	18	523

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap CSMD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →