DEPDC7

Chr 11

DEP domain containing 7

Also known as: TR2, dJ85M6.4

NCBI Gene: 91614 ENSG00000121690 UniProt: Q96QD5 OMIM: 612294

DEPDC7 encodes a protein predicted to be involved in intracellular signal transduction. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy or early childhood. The gene shows extreme constraint against loss-of-function variants (pLI ~1.0), indicating that biallelic mutations likely result in severe neurodevelopmental impairment.

OMIM ResearchSummary from RefSeq

Predicted to be involved in intracellular signal transduction. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.10

LOEUF

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.17

OE 0.75 (0.52–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.96Z-score

OE missense 0.83 (0.74–0.93)

211 obs / 254.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.52–1.10)

0≤0.351.4

Missense OE?0.83 (0.74–0.93)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

LoF obs/exp: 19 / 25.4Missense obs/exp: 211 / 254.0Syn Z: 1.77

Background carrier burden — how many people carry a rare variant somewhere in DEPDC7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

585 rare PASS variants

Rare truncating (LoF)

1 in 1,400

114 rare PASS variants

Rare synonymous (reference)

1 in 260

204 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DEPDC7. 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 180	1 in 1,600
South Asian	~43k	1 in 87	1 in 570
Remaining (unassigned)	~30k	1 in 100	1 in 880
European (Finnish)	~27k	1 in 650	1 in 3,300
Admixed American	~22k	1 in 150	1 in 1,700
African / African American	~21k	1 in 71	1 in 560
East Asian	~20k	1 in 190	1 in 880
Ashkenazi Jewish	~13k	1 in 650	1 in 2,600
Middle Eastern	~2,884	1 in 81	≈ 1 in 1,400

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): 7 of 9 coding exons well covered in gnomAD exomes; exons 3, 8 marginal. Genomes: all 9.? see exons ↓