AK9

protein-coding

adenylate kinase 9, the group of Adenylate kinases

Gene summary

The protein encoded by this gene catalyzes the interconversion of nucleosides, possessing both nucleoside monophosphate and diphosphate kinase activities. The encoded protein uses these interconversions to maintain nucleoside homeostasis. [provided by RefSeq, Jul 2016]

Previous symbols:

C6orf224
AKD2
C6orf199
AKD1

MANE transcript

NM_001145128.3

Inheritance

ClinVar variants

P:6U:196B:23

Top phenotype

Spermatogenic failure 89

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr6:109,492,855-109,691,217

External References & Databases

Ensembl (ENSG00000155085)

Transcript & Mutation Effects

hg38 • Region Span ~198.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Spermatogenic failure 89AR

Manifestation: Genitourinary

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: 37713809

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AK9 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 196

not providedTotal: 20

Spermatogenic failure 89Total: 6

AK9-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001145128.3. 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			1 clinvar	3 clinvar	6 clinvar	10
missense	1 clinvar	1 clinvar	191 clinvar	11 clinvar	3 clinvar	207
nonsense						0
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)		2 clinvar	4 clinvar			6
Total	3	3	196	14	9	225

Highest pathogenic variant AF is 0.0002748504

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001145128.3	RefSeq	NP_001138600.2	40	MANE Select
ENST00000424296.7	Ensembl	ENSP00000410186.2	40	MANE Select
NM_001329602.2	RefSeq	NP_001316531.1	11	Standard
NM_001329603.2	RefSeq	NP_001316532.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ak9	Danio rerio	Structure: otolith Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

ak9

Danio rerio

Structure: otolith

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Metabolism of nucleotides
Interconversion of nucleotide di- and triphosphates
Metabolism

Biological Process

dADP phosphorylation
dGDP phosphorylation
AMP phosphorylation
ATP generation from ADP
nucleobase-containing small molecule interconversion

Molecular Function

nucleoside diphosphate kinase activity
ATP binding
nucleoside kinase activity
nucleoside monophosphate kinase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000424296
Coding exons: 40
Length: 198362
Individuals with no LoFs: 125607
Homozygous LoFs: 0
Heterozygous LoFs: 141
Defined: 125748
p: 0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.19	725	911	0.795	0.0000445	12605
Missense (PolyPhen)		259	308.46	0.83965		4256
Synonymous	2.34	254	306	0.830	0.0000152	3325
Loss of Function	3.71	57	96.3	0.592	0.00000453	1418

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.0012	0.00098	notable
Ashkenazi Jewish	0.0013	0.0013	notable
East Asian	0.00028	0.00027	rare
Finnish	0.00024	0.00023	rare
European (Non-Finnish)	0.00050	0.00049	rare
South Asian	0.00067	0.00062	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Has both nucleoside monophosphate and diphosphate kinase activities. Catalyzes the phosphorylation of AMP, dAMP, CMP and dCMP with ATP as phosphate donor and of CMP with GTP as phosphate donor. Also catalyzes the production of ATP, CTP, GTP, UTP, dATP, dCTP, dGTP and TTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donor. Shows substrate preference of CDP > UDP > ADP > GDP > TDP. {ECO:0000269|PubMed:23416111}.;

Recessive Scores

pRec: 0.0711

Intolerance Scores

RVIS EVS: 1.72
RVIS percentile EVS: 96.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High