AMPD3

protein-coding

adenosine monophosphate deaminase 3, the group of Adenosine deaminase family

Gene summary

This gene encodes a member of the AMP deaminase gene family. The encoded protein is a highly regulated enzyme that catalyzes the hydrolytic deamination of adenosine monophosphate to inosine monophosphate, a branch point in the adenylate catabolic pathway. This gene encodes the erythrocyte (E) isoforms, whereas other family members encode isoforms that predominate in muscle (M) and liver (L) cells. Mutations in this gene lead to the clinically asymptomatic, autosomal recessive condition erythrocyte AMP deaminase deficiency. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001025389.2

Inheritance

AR, AD

ClinVar variants

P:4U:149B:25

Top phenotype

Erythrocytic AMP deaminase deficiency

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr11:10,308,313-10,507,579

External References & Databases

Ensembl (ENSG00000133805)

Transcript & Mutation Effects

hg38 • Region Span ~199.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

erythrocyte AMP deaminase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020734

Submitter: PanelApp Australia

adenosine monophosphate deaminase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013028

Submitter: Orphanet

Clinical Genomic Database (CGD)

Erythrocytic AMP deaminase deficiencyAD/AR

Manifestation: General

Intervention: General

Rationale: The condition may not be clinically relevant

Refs: 3804327; 7881427; 8004104

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AMPD3 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 111

Erythrocyte AMP deaminase deficiencyTotal: 75

not providedTotal: 20

AMPD3-related disorderTotal: 14

Adenosine monophosphate deaminase deficiencyTotal: 1

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001025389.2. 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			14 clinvar	18 clinvar	1 clinvar	33
missense	1 clinvar		131 clinvar	5 clinvar	1 clinvar	138
nonsense			1 clinvar			1
start loss						0
frameshift		2 clinvar				2
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	1	3	149	23	2	178

Highest pathogenic variant AF is 0.0002446969

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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_001025389.2	RefSeq	NP_001020560.1	14	MANE Select
ENST00000396553.7	Ensembl	ENSP00000379801.2	14	MANE Select
NM_000480.3	RefSeq	NP_000471.1	15	Standard
NM_001025390.2	RefSeq	NP_001020561.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine metabolism - Homo sapiens (human)
Neutrophil degranulation
Metabolism of nucleotides
Innate Immune System
Immune System

Biological Process

AMP catabolic process
IMP salvage
erythrocyte homeostasis
purine-containing compound salvage
neutrophil degranulation

Molecular Function

AMP deaminase activity
protein binding
metal ion binding

Cellular Component

extracellular region
cytosol
secretory granule lumen
ficolin-1-rich granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396554
Coding exons: 15
Length: 199267
Individuals with no LoFs: 125562
Homozygous LoFs: 0
Heterozygous LoFs: 186
Defined: 125748
p: 0.000740

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.667	416	456	0.912	0.0000303	5121
Missense (PolyPhen)		184	203.2	0.90549		2242
Synonymous	-0.935	206	190	1.09	0.0000128	1488
Loss of Function	2.02	25	38.5	0.649	0.00000218	444

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.0016	0.0016	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0018	0.0018	notable
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00040	0.00040	rare
South Asian	0.00069	0.00069	rare
Other	0.0021	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: AMP deaminase plays a critical role in energy metabolism.;
Disease: DISEASE: Adenosine monophosphate deaminase deficiency erythrocyte type (AMPDDE) [MIM:612874]: A metabolic disorder due to lack of activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic condition characterized by a 50% increase in steady-state levels of ATP in affected cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and have no hematologic disorders. {ECO:0000269|PubMed:11139257, ECO:0000269|PubMed:7881427, ECO:0000269|PubMed:8004104, ECO:0000269|PubMed:9598089}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.307

Intolerance Scores

LoFtool: 0.0203
RVIS EVS: -0.21
RVIS percentile EVS: 37.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.241

Gene Damage Prediction

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