MEDAG

Chr 13

mesenteric estrogen dependent adipogenesis

Also known as: AWMS3, C13orf33, MEDA-4, MEDA4, hAWMS3

NCBI Gene: 84935 ENSG00000102802 UniProt: Q5VYS4

The MEDAG protein promotes adipocyte differentiation, lipid accumulation, and glucose uptake in mature fat cells. Mutations cause autosomal recessive developmental delay, seizures, and hypotonia. This gene is not highly constrained against loss-of-function variants, with neurological symptoms being the primary clinical manifestations rather than metabolic dysfunction.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in positive regulation of fat cell differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.23

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.98

OE 0.70 (0.42–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.43Z-score

OE missense 1.10 (0.97–1.25)

166 obs / 151.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.70 (0.42–1.23)

0≤0.351.4

Missense OE?1.10 (0.97–1.25)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 9 / 12.8Missense obs/exp: 166 / 151.0Syn Z: 1.33

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

429 rare PASS variants

Rare truncating (LoF)

1 in 980

71 rare PASS variants

Rare synonymous (reference)

1 in 150

163 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MEDAG. 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 170	1 in 1,200
South Asian	~43k	1 in 140	1 in 320
Remaining (unassigned)	~30k	1 in 92	1 in 610
European (Finnish)	~27k	1 in 400	1 in 1,800
Admixed American	~22k	1 in 120	1 in 1,200
African / African American	~21k	1 in 120	1 in 650
East Asian	~20k	1 in 120	1 in 1,400
Ashkenazi Jewish	~13k	1 in 320	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,300

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 5.? see exons ↓