DISP3

Chr 1

dispatched RND transporter family member 3

Also known as: PTCHD2

NCBI Gene: 57540 ENSG00000204624 UniProt: Q9P2K9 OMIM: 611251

DISP3 encodes a protein that regulates neuronal proliferation and differentiation while contributing to cholesterol homeostasis and lipid droplet formation in cells. Mutations cause autosomal recessive intellectual disability with dysmorphic features and seizures. The gene is highly constrained against loss-of-function variants (LOEUF 0.548), suggesting complete loss of function is poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Involved in negative regulation of neuron differentiation; positive regulation of lipid metabolic process; and positive regulation of neural precursor cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.55

Clinical Summary— DISP3

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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

14 VUS of 61 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.000

Z-score 4.44

OE 0.39 (0.28–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.52Z-score

OE missense 0.86 (0.81–0.91)

772 obs / 900.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.28–0.55)

0≤0.351.4

Missense OE?0.86 (0.81–0.91)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 24 / 61.6Missense obs/exp: 772 / 900.2Syn Z: 0.80

This gene — mechanism propensity

0.6453th %ile

GOF

0.6149th %ile

LOF

0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS14

Likely Benign21

Benign20

VUS

Likely Benign

Benign

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	1	13	0	0	14
Likely Benign	0	3	3	15	21
Benign	0	10	1	9	20
Total	1	26	4	24	55

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap DISP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →