DEPTOR

Chr 8ARAD

DEP domain containing MTOR interacting protein

Also known as: DEP.6, DEPDC6, hDEPTOR

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Spondyloepimetaphyseal dysplasia, Krakow typeMIM #618162
AR
Metaphyseal chondrodysplasia, Murk Jansen typeMIM #156400
AD
0
Active trials
32
Pubs (1 yr)
53
P/LP submissions
0%
P/LP missense
1.43
LOEUF
GOF
Mechanism· predicted
Clinical SummaryDEPTOR
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 65 VUS of 142 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.000
Z-score 0.15
OE 0.96 (0.661.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.09Z-score
OE missense 0.98 (0.891.09)
245 obs / 248.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.96 (0.661.43)
00.351.4
Missense OE0.98 (0.891.09)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 18 / 18.7Missense obs/exp: 245 / 248.9Syn Z: 0.46
DN
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

142 submitted variants in ClinVar

Classification Summary

Pathogenic53
VUS65
Likely Benign4
Conflicting1
53
Pathogenic
65
VUS
4
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
0
0
0
VUS
0
60
5
0
65
Likely Benign
0
1
0
3
4
Benign
0
0
0
0
0
Conflicting
1
Total061583123

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

View in ClinVar →

Protein Context — Lollipop Plot

DEPTOR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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