MAEA

Chr 4

macrophage erythroblast attacher, E3 ubiquitin ligase

Also known as: EMLP, EMP, GID9, HLC-10, P44EMLP, PIG5

NCBI Gene: 10296 ENSG00000090316 UniProt: Q7L5Y9 OMIM: 606801

This gene encodes a core component of the CTLH E3 ubiquitin-protein ligase complex that mediates protein degradation and also facilitates erythroblast attachment to macrophages during red blood cell maturation. Mutations cause autosomal recessive neurodevelopmental disorder with seizures, microcephaly, and brain atrophy, typically presenting in infancy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.517), consistent with its role in essential cellular processes including cell proliferation and neuronal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that mediates the attachment of erythroblasts to macrophages. This attachment promotes terminal maturation and enucleation of erythroblasts, presumably by suppressing apoptosis. The encoded protein is an integral membrane protein with the N-terminus on the extracellular side and the C-terminus on the cytoplasmic side of the cell. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

OMIM ResearchGenerating clinical summary…

LOEUF 0.52

Clinical Summary— MAEA

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

45 VUS of 59 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.227

Z-score 3.15

OE 0.25 (0.13–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.57Z-score

OE missense 0.57 (0.50–0.65)

158 obs / 278.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.25 (0.13–0.52)

0≤0.351.4

Missense OE?0.57 (0.50–0.65)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 5 / 20.3Missense obs/exp: 158 / 278.7Syn Z: -1.29

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

VUS45

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	44	0	45
Likely Benign	0	1	1	2
Benign	0	0	2	2
Total	1	45	3	49

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

View in ClinVar →

149 pathogenic / likely-pathogenic (of 167) ClinVar copy-number / structural variants overlap MAEA — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →