AMDHD1
protein-codingamidohydrolase domain containing 1, the group of M38 metallopeptidases
Gene summary
Predicted to enable imidazolonepropionase activity. Predicted to be involved in L-histidine catabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AMDHD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_152435.3. 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 | 3 | 3 | ||||
| missense | 58 | 1 | 59 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 63 | 1 | 0 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_689648.2 | 9 | MANE Select | |
| Ensembl | ENSP00000266736.2 | 9 | MANE Select | |
| Ensembl | ENSP00000448632.1 | 3 | Standard | |
| Ensembl | ENSP00000448918.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Histidine metabolism - Homo sapiens (human)
- Histidine Metabolism
- Histidinemia
- Histidine catabolism
- Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism
Biological Process
- histidine catabolic process
- histidine catabolic process to glutamate and formamide
- histidine catabolic process to glutamate and formate
Molecular Function
- molecular_function
- hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides
- metal ion binding
- imidazolonepropionase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000266736
- Coding exons
- 9
- Length
- 25300
- Individuals with no LoFs
- 125673
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 75
- Defined
- 125748
- p
- 0.000298
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.304 | 254 | 241 | 1.06 | 0.0000139 | 2754 |
| Missense (PolyPhen) | 92 | 98.751 | 0.93164 | 1070 | ||
| Synonymous | 0.769 | 84 | 93.5 | 0.899 | 0.00000597 | 838 |
| Loss of Function | 1.02 | 14 | 18.8 | 0.746 | 9.47e-7 | 231 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00037 | 0.00037 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0015 | 0.0015 | notable |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00020 | 0.00020 | rare |
| South Asian | 0.00034 | 0.00033 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.793
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.312
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |