DEPTOR

Chr 8ARAD

DEP domain containing MTOR interacting protein

Also known as: DEP.6, DEPDC6, hDEPTOR

NCBI Gene: 64798 ENSG00000155792 UniProt: Q8TB45 OMIM: 614776

DEPTOR encodes a negative regulator of mTORC1 and mTORC2 complexes that inhibits MTOR kinase activity and induces autophagy. Mutations cause spondyloepimetaphyseal dysplasia (Krakow type) and metaphyseal chondrodysplasia (Murk Jansen type), skeletal dysplasias affecting bone and cartilage development. The gene shows both autosomal recessive and autosomal dominant inheritance patterns and is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables phosphatidic acid binding activity and protein serine/threonine kinase inhibitor activity. Involved in several processes, including negative regulation of TOR signaling; negative regulation of cell size; and negative regulation of protein kinase activity. Is active in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismAR/ADLOEUF 1.432 OMIM phenotypes

Clinical Summary— DEPTOR

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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

61 VUS of 85 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.15

OE 0.96 (0.66–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.89–1.09)

245 obs / 248.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.96 (0.66–1.43)

0≤0.351.4

Missense OE?0.98 (0.89–1.09)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 18 / 18.7Missense obs/exp: 245 / 248.9Syn Z: 0.46

This gene — mechanism propensity

0.5477th %ile

GOF

0.6442th %ile

LOF

0.49top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

85 submitted variants in ClinVar

ClinVar

Classification Summary

VUS61

Likely Benign4

Conflicting1

VUS

Likely 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	0	61	0	0	61
Likely Benign	0	1	0	3	4
Benign	0	0	0	0	0
Conflicting	—				1
Total	0	62	0	3	66

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

View in ClinVar →

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