AMPD2

protein-coding

adenosine monophosphate deaminase 2, the group of Adenosine deaminase family

Gene summary

The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MANE transcript

NM_001368809.2

Inheritance

ClinVar variants

P:55U:205B:136

Top phenotype

Pontocerebellar hypoplasia type 9; Spastic paraplegia 63

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr1:109,616,104-109,632,051

External References & Databases

Ensembl (ENSG00000116337)

Transcript & Mutation Effects

hg38 • Region Span ~15.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spastic paraplegia 63LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014305

Submitter: Labcorp Genetics (formerly Invitae)

pontocerebellar hypoplasia type 9DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014351

Submitter: G2P

hereditary spastic paraplegia 63SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014305

Submitter: Orphanet

pontocerebellar hypoplasia type 9SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014351

Submitter: Orphanet

pontocerebellar hypoplasia type 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014351

Submitter: PanelApp Australia

pontocerebellar hypoplasia type 9DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014351

Submitter: Ambry Genetics

pontocerebellar hypoplasia type 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014351

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Pontocerebellar hypoplasia type 9; Spastic paraplegia 63AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 23911318; 24482476; 27066553

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMPD2 variants in ClinVar

17 Conditions Cataloged

Pontocerebellar hypoplasia type 9Total: 363

Hereditary spastic paraplegia 63Total: 348

Inborn genetic diseasesTotal: 102

not providedTotal: 90

not specifiedTotal: 26

AMPD2-related disorderTotal: 23

Pontoneocerebellar hypoplasiaTotal: 7

Intellectual disabilityTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001368809.2. 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			4 clinvar	131 clinvar	4 clinvar	139
missense	3 clinvar	13 clinvar	194 clinvar	1 clinvar		211
nonsense	8 clinvar	5 clinvar	1 clinvar			14
start loss						0
frameshift	8 clinvar	7 clinvar	1 clinvar			16
splice donor/acceptor (+/-2bp)	3 clinvar	8 clinvar	5 clinvar			16
Total	22	33	205	132	4	396

Highest pathogenic variant AF is 0.000032927845

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001368809.2	RefSeq	NP_001355738.1	18	MANE Select
ENST00000528667.7	Ensembl	ENSP00000436541.2	18	MANE Select
NM_001257361.2	RefSeq	NP_001244290.1	17	Standard
NM_001308170.1	RefSeq	NP_001295099.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Metabolism of nucleotides
Metabolism
Nucleotide salvage
Purine salvage

Biological Process

IMP biosynthetic process
IMP salvage
purine-containing compound salvage
cyclic purine nucleotide metabolic process
energy homeostasis

Molecular Function

AMP deaminase activity
protein binding
metal ion binding

Cellular Component

cellular_component
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256578
Coding exons: 18
Length: 15948
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125747
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.83	379	569	0.666	0.0000379	5719
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000049	0.000046	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.217

Intolerance Scores

LoFtool: 0.0601
RVIS EVS: -1.46
RVIS percentile EVS: 3.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.269

Gene Damage Prediction

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