AMMECR1

Chr XXLR

AMMECR nuclear protein 1

Also known as: AMMERC1, MFHIEN

NCBI Gene: 9949ENSG00000101935UniProt: Q9Y4X0

The exact function of this gene is not known, however, submicroscopic deletion of the X chromosome including this gene, COL4A5, and FACL4 genes, result in a contiguous gene deletion syndrome, the AMME complex (Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

Primary Disease Associations & Inheritance

Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosisMIM #300990
XLR
UniProtAMME complex
163
ClinVar variants
82
Pathogenic / LP
0.82
pLI score
0
Active trials
Clinical Summary— AMMECR1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
82 Pathogenic / Likely Pathogenic· 64 VUS of 163 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.08Z-score
OE missense 0.73 (0.61–0.87)
90 obs / 123.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.03–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.61–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 1 / 10.0Missense obs/exp: 90 / 123.8Syn Z: 0.27

ClinVar Variant Classifications

163 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
4
0
66
0
70
Likely Pathogenic
4
1
7
0
12
VUS
0
47
17
0
64
Likely Benign
0
2
0
7
9
Benign
0
0
3
2
5
Conflicting
—3
Total850939163

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis

MIM #300990

Molecular basis of disorder known

X-linked recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
New developments in the genetic diagnosis of short stature.
Jee YH et al.·Curr Opin Pediatr
2018Review
Xq22.3q23 microdeletion harboring TMEM164 and AMMECR1 genes: Two case reports confirming a recognizable phenotype with short stature, midface hypoplasia, intellectual delay, and elliptocytosis.
Poreau B et al.·Am J Med Genet A
2019Case report
AMMECR1: a single point mutation causes developmental delay, midface hypoplasia and elliptocytosis.
Andreoletti G et al.·J Med Genet
2017
Hearing loss, cleft palate, and congenital hip dysplasia in female carriers of an intragenic deletion of AMMECR1.
Koene S et al.·Am J Med Genet A
2022Case report
Diagnostic yield of genome sequencing for prenatal diagnosis of fetal structural anomalies.
Wang Y et al.·Prenat Diagn
2022
Xq22.3-q23 deletion including ACSL4 in a patient with intellectual disability.
Gazou A et al.·Am J Med Genet A
2013Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools