DEPTOR

Chr 8

DEP domain containing MTOR interacting protein

Also known as: DEP.6, DEPDC6, hDEPTOR

NCBI Gene: 64798 ENSG00000155792 UniProt: Q8TB45 OMIM: 612974

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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.43

LOEUF

GOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in DEPTOR?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 91

555 rare PASS variants

Rare truncating (LoF)

1 in 1,500

110 rare PASS variants

Rare synonymous (reference)

1 in 280

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DEPTOR. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 1,900
South Asian	~43k	1 in 100	1 in 440
Remaining (unassigned)	~30k	1 in 81	1 in 1,400
European (Finnish)	~27k	1 in 160	≈ 1 in 6,500
Admixed American	~22k	1 in 110	1 in 510
African / African American	~21k	1 in 100	1 in 1,200
East Asian	~20k	1 in 99	1 in 1,700
Ashkenazi Jewish	~13k	1 in 620	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 120	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 9 coding exons well covered in gnomAD exomes. Genomes: 8 of 9 (exon 6 below).? see exons ↓