MEAK7

Chr 16

MTOR associated protein MEAK7

Also known as: EAK7, KIAA1609, TLDC1, mEAK-7

NCBI Gene: 57707 ENSG00000140950 UniProt: Q6P9B6 OMIM: 619331

The protein activates mTOR signaling by recruiting mTOR to the lysosome and regulating cell proliferation and migration through RPS6KB2 activation and EIF4EBP1 repression. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. The gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Involved in several processes, including TOR signaling; positive regulation of protein localization to lysosome; and response to insulin. Located in cytosol; lysosomal membrane; and nuclear lumen. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 1.78

Clinical Summary— MEAK7

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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

133 VUS of 176 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.78LOEUF

pLI 0.000

Z-score -1.14

OE 1.29 (0.93–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-3.83Z-score

OE missense 1.66 (1.53–1.79)

445 obs / 268.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.29 (0.93–1.78)

0≤0.351.4

Missense OE?1.66 (1.53–1.79)

0≤0.61.4

Synonymous OE?1.56

0≤1.21.6

LoF obs/exp: 23 / 17.8Missense obs/exp: 445 / 268.5Syn Z: -4.67

ClinVar Variant Classifications

176 submitted variants in ClinVar

ClinVar

Classification Summary

VUS133

Likely Benign13

Benign10

Conflicting1

133

VUS

Likely Benign

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	133	0	0	133
Likely Benign	1	10	0	2	13
Benign	0	5	2	3	10
Conflicting	—				1
Total	1	148	2	5	157

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap MEAK7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →