AMPD2

adenosine monophosphate deaminase 2, the group of Adenosine deaminase family

Basic information

Region (hg38): 1:109616103-109632051

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

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.

• Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9 (184 variants)
• not provided (100 variants)
• Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63 (75 variants)
• Pontocerebellar hypoplasia type 9 (59 variants)
• Hereditary spastic paraplegia 63 (46 variants)
• Inborn genetic diseases (33 variants)
• not specified (7 variants)
• Hereditary spastic paraplegia (2 variants)
• Pontoneocerebellar hypoplasia (1 variants)
• Spastic ataxia (1 variants)
• Abnormality of the nervous system (1 variants)
• Brain malformation;Global developmental delay;Seizure (1 variants)
• Intellectual disability (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	71	7	79
missense	1	8	129	1		139
nonsense	3	3	1			7
start loss						0
frameshift	3	3	1			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	2			1	5
splice region			6	9		15
non coding	1		11	60	29	101
Total	10	16	146	132	37

Highest pathogenic variant AF is 0.0000131

Variants in AMPD2

This is a list of pathogenic ClinVar variants found in the AMPD2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-109619568-C-T			Benign (Jul 15, 2018)
1-109619696-G-C			Likely benign (Apr 24, 2019)
1-109619926-C-T			Benign (Jul 06, 2018)
1-109620296-T-C		Hereditary spastic paraplegia 63 • Pontocerebellar hypoplasia type 9	Benign (Apr 11, 2023)
1-109620373-A-G			Likely benign (Jul 17, 2018)
1-109620454-A-G			Benign (Jul 06, 2018)
1-109621015-T-G		Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63	Uncertain significance (Jun 13, 2023)
1-109621025-T-C		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Likely benign (Sep 22, 2019)
1-109621027-G-A		Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63	Uncertain significance (Sep 27, 2022)
1-109621043-C-T		Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63	Likely benign (Nov 28, 2022)
1-109621057-G-C		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Uncertain significance (May 09, 2023)
1-109621064-G-A		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Likely benign (Jun 10, 2023)
1-109621081-T-C		Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63	Uncertain significance (May 06, 2022)
1-109621082-G-T		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Likely benign (Dec 02, 2021)
1-109621101-G-T		Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63	Uncertain significance (Sep 24, 2018)
1-109621109-T-C		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Likely benign (Feb 05, 2022)
1-109621124-C-G		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Benign/Likely benign (Jan 29, 2024)
1-109621130-C-G		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Uncertain significance (Aug 23, 2022)
1-109621129-G-GCCGGTGCCGCTCAGACTCCC		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Pathogenic (Mar 19, 2022)
1-109621131-C-T		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 21, 2022)
1-109621133-G-T		Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63	Likely benign (Mar 20, 2022)
1-109621138-G-A		Hereditary spastic paraplegia 63;Pontocerebellar hypoplasia type 9	Uncertain significance (Sep 15, 2021)
1-109621146-T-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
1-109621149-C-A		Inborn genetic diseases	Uncertain significance (Nov 01, 2022)
1-109621157-C-T		Pontocerebellar hypoplasia type 9;Hereditary spastic paraplegia 63	Likely benign (Nov 27, 2023)

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