AMMECR1
protein-codingAMMECR nuclear protein 1, the group of Small nucleolar RNA protein coding host genes
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~246.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010263
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010516
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0010516
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010516
Submitter: Illumina
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Craniofacial; Hematologic; Musculoskeletal; Renal
Intervention: Hematologic
Rationale: Ellipsocytosis requiring red blood cell transfusion has been described, and awareness may allow early diagnosis and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AMMECR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015365.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 13 | 1 | 20 | ||
| missense | 1 | 1 | 68 | 7 | 77 | |
| nonsense | 2 | 3 | 7 | 12 | ||
| start loss | 0 | |||||
| frameshift | 4 | 1 | 2 | 7 | ||
| splice donor/acceptor (+/-2bp) | 4 | 9 | 13 | |||
| Total | 7 | 9 | 92 | 20 | 1 | 129 |
Highest pathogenic variant AF is 0.000001854075
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056180.1 | 6 | MANE Select | |
| Ensembl | ENSP00000262844.5 | 6 | MANE Select | |
| RefSeq | NP_001020751.1 | 5 | Standard | |
| RefSeq | NP_001165160.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ammecr1 | Danio rerio | Structure: post-vent region Quality: kinked abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- biological_process
Molecular Function
- protein binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262844
- Coding exons
- 6
- Length
- 246048
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 90 | 124 | 0.727 | 0.00000918 | 2095 |
| Missense (PolyPhen) | 19 | 45.226 | 0.42011 | 736 | ||
| Synonymous | 0.273 | 47 | 49.4 | 0.951 | 0.00000353 | 710 |
| Loss of Function | 2.64 | 1 | 10.0 | 0.0995 | 6.96e-7 | 187 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Disease
- DISEASE: Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis (MFHIEN) [MIM:300990]: An X-linked recessive disorder with onset in early childhood, characterized by midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis. Variable clinical features include anemia, and mild early motor or speech delay. {ECO:0000269|PubMed:27811305, ECO:0000269|PubMed:28089922}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis (ATS-MR) [MIM:300194]: A X-linked contiguous gene deletion syndrome characterized by glomerulonephritis, sensorineural hearing loss, mental retardation, midface hypoplasia and elliptocytosis. {ECO:0000269|PubMed:10049589}. Note=The gene represented in this entry may be involved in disease pathogenesis.;
Recessive Scores
- pRec
- 0.338
Intolerance Scores
- LoFtool
- 0.0853
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |