DBNDD1

Chr 16

dysbindin domain containing 1

NCBI Gene: 79007 ENSG00000003249 UniProt: Q9H9R9 OMIM: 620388

The DBNDD1 protein is predicted to regulate signal transduction and localize to the cytoplasm. Mutations cause disease through a predicted gain-of-function mechanism, though specific associated neurological conditions have not been definitively established. The inheritance pattern and detailed clinical phenotype remain to be fully characterized.

OMIM ResearchSummary from RefSeq, Mechanism

Predicted to be involved in regulation of signal transduction. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.53

Clinical Summary— DBNDD1

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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

33 VUS of 37 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.53LOEUF

pLI 0.000

Z-score 0.47

OE 0.83 (0.47–1.53)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.21Z-score

OE missense 0.94 (0.81–1.11)

108 obs / 114.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.47–1.53)

0≤0.351.4

Missense OE?0.94 (0.81–1.11)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 7 / 8.5Missense obs/exp: 108 / 114.4Syn Z: -0.58

This gene — mechanism propensity

0.6260th %ile

GOF

0.77top 25%

LOF

0.3647th %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

37 submitted variants in ClinVar

ClinVar

Classification Summary

VUS33

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	33	33
Likely Benign	2	2
Benign	0	0
Total	35	35

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

View in ClinVar →

35 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap DBNDD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →