AMMECR1

Chr XXLR

AMMECR nuclear protein 1

Also known as: AMMERC1, MFHIEN

NCBI Gene: 9949ENSG00000101935UniProt: Q9Y4X0OMIM: 300195

The exact function of the AMMECR1 protein is unknown, but deletions involving this gene along with neighboring genes cause AMME complex, characterized by midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis. This X-linked recessive condition is part of a contiguous gene deletion syndrome that affects multiple organ systems including craniofacial development, auditory function, hematologic systems, and kidneys. The gene shows high constraint against loss-of-function variants (pLI 0.82, LOEUF 0.47), suggesting intolerance to protein loss.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismXLRLOEUF 0.471 OMIM phenotype
Clinical Summary— AMMECR1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 64 VUS of 202 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
0.47LOEUF
pLI 0.821
Z-score 2.64
OE 0.10 (0.03–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.08Z-score
OE missense 0.73 (0.61–0.87)
90 obs / 123.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.03–0.47)
0≤0.351.4
Missense OE0.73 (0.61–0.87)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 1 / 10.0Missense obs/exp: 90 / 123.8Syn Z: 0.27
DN
0.2698th %ile
GOF
0.3788th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.47

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

202 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic70
Likely Pathogenic12
VUS64
Likely Benign9
Benign5
Conflicting3
70
Pathogenic
12
Likely Pathogenic
64
VUS
9
Likely Benign
5
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
65
0
70
Likely Pathogenic
7
1
4
0
12
VUS
3
48
13
0
64
Likely Benign
0
2
0
7
9
Benign
0
0
3
2
5
Conflicting
—3
Total1551859163

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

View in ClinVar →

Protein Context — Lollipop Plot

AMMECR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients