DOP1A

Chr 6

DOP1 leucine zipper like protein A

Also known as: DOP1, DOPEY1, KIAA1117, dJ202D23.2

NCBI Gene: 23033 ENSG00000083097 UniProt: Q5JWR5 OMIM: 616823

The protein is involved in trafficking between the late Golgi and early endosomes and participates in endoplasmic reticulum organization. Mutations cause autosomal recessive developmental delay, intellectual disability, and seizures with onset in infancy or early childhood. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.25), indicating intolerance to functional disruption.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.25

Clinical Summary— DOP1A

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 272 VUS of 379 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.25LOEUF

pLI 1.000

Z-score 8.37

OE 0.18 (0.12–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.32Z-score

OE missense 0.74 (0.70–0.78)

919 obs / 1249.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.18 (0.12–0.25)

0≤0.351.4

Missense OE?0.74 (0.70–0.78)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 21 / 119.9Missense obs/exp: 919 / 1249.5Syn Z: 2.15

This gene — mechanism propensity

0.4487th %ile

GOF

0.3887th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 63% of P/LP variants are LoF · LOEUF 0.25

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

379 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic5

VUS272

Likely Benign49

Benign7

Conflicting3

Pathogenic

Likely Pathogenic

272

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	2	0	0	3
Likely Pathogenic	4	1	0	0	5
VUS	2	268	2	0	272
Likely Benign	0	10	13	26	49
Benign	0	0	5	2	7
Conflicting	—				3
Total	7	281	20	28	339

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap DOP1A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →