AMPD2

adenosine monophosphate deaminase 2, the group of Adenosine deaminase family

Basic information

Region (hg38): 1:109616104-109632051

Links

ENSG00000116337

∙ NCBI:271 ∙ OMIM:102771 ∙ HGNC:469 ∙ Uniprot:Q01433 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

pontocerebellar hypoplasia type 9 (Definitive), mode of inheritance: AR
pontocerebellar hypoplasia type 9 (Strong), mode of inheritance: AR
pontocerebellar hypoplasia type 9 (Supportive), mode of inheritance: AR
hereditary spastic paraplegia 63 (Supportive), mode of inheritance: AR
pontocerebellar hypoplasia type 9 (Strong), mode of inheritance: AR
hereditary spastic paraplegia 63 (Limited), mode of inheritance: Unknown
pontocerebellar hypoplasia type 9 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia type 9; Spastic paraplegia 63	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23911318; 24482476; 27066553

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AMPD2 gene.

Pontocerebellar_hypoplasia_type_9 (320 variants)
Hereditary_spastic_paraplegia_63 (304 variants)
not_provided (85 variants)
Inborn_genetic_diseases (83 variants)
AMPD2-related_disorder (19 variants)
not_specified (12 variants)
Pontoneocerebellar_hypoplasia (4 variants)
Intellectual_disability (2 variants)
Hereditary_spastic_paraplegia (2 variants)
Global_developmental_delay (1 variants)
Microcephaly (1 variants)
Brain_malformation (1 variants)
Abnormality_of_the_nervous_system (1 variants)
Spastic_ataxia (1 variants)
Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AMPD2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001368809.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	102 clinvar	5 clinvar	109
missense	3 clinvar	12 clinvar	176 clinvar	1 clinvar		192
nonsense	6 clinvar	4 clinvar	1 clinvar			11
start loss						0
frameshift	7 clinvar	8 clinvar	1 clinvar			16
splice donor/acceptor (+/-2bp)	2 clinvar	5 clinvar			1 clinvar	8
Total	18	29	180	103	6

Highest pathogenic variant AF is 0.0000329278

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AMPD2	protein_coding	protein_coding	ENST00000256578	18	15948

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.51e-7	1.00	125702	0	45	125747	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.83	379	569	0.666	0.0000379	5719
Missense in Polyphen		112	242.46	0.46192		2517
Synonymous	0.464	228	237	0.962	0.0000155	1758
Loss of Function	3.42	18	41.8	0.430	0.00000214	469

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000238	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000494	0.0000462
European (Non-Finnish)	0.000268	0.000264
Middle Eastern	0.000109	0.000109
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle. {ECO:0000269|PubMed:23911318}.;
Disease: DISEASE: Pontocerebellar hypoplasia 9 (PCH9) [MIM:615809]: A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH9 features include severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination. {ECO:0000269|PubMed:23911318}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 63, autosomal recessive (SPG63) [MIM:615686]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. {ECO:0000269|PubMed:24482476}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Purine metabolism - Homo sapiens (human);Metabolism of nucleotides;Metabolism;Nucleotide salvage;Purine salvage;Purine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

pRec: 0.217

Intolerance Scores

loftool: 0.0601
rvis_EVS: -1.46
rvis_percentile_EVS: 3.79

Haploinsufficiency Scores

pHI: 0.238
hipred: Y
hipred_score: 0.637
ghis: 0.553

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.269

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Ampd2
Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: IMP biosynthetic process;IMP salvage;purine-containing compound salvage;cyclic purine nucleotide metabolic process;energy homeostasis
Cellular component: cellular_component;cytosol
Molecular function: AMP deaminase activity;protein binding;metal ion binding