FASTKD2

Chr 2AR

FAST kinase domains 2

NCBI Gene: 22868ENSG00000118246UniProt: Q9NYY8

Plays an important role in assembly of the mitochondrial large ribosomal subunit (PubMed:25683715). As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation (PubMed:25683715, PubMed:26370583, PubMed:27667664). May play a role in mitochondrial apoptosis

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 44MIM #618855
AR
557
ClinVar variants
45
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FASTKD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 257 VUS of 557 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.75LOEUF
pLI 0.000
Z-score 2.60
OE 0.48 (0.32–0.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.67Z-score
OE missense 0.90 (0.82–0.99)
328 obs / 363.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.48 (0.32–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 14 / 29.2Missense obs/exp: 328 / 363.7Syn Z: -0.97

ClinVar Variant Classifications

557 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic13
VUS257
Likely Benign103
Benign17
Conflicting20
32
Pathogenic
13
Likely Pathogenic
257
VUS
103
Likely Benign
17
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
26
0
32
Likely Pathogenic
9
1
3
0
13
VUS
1
183
68
5
257
Likely Benign
0
17
42
44
103
Benign
0
1
15
1
17
Conflicting
—20
Total1520315450442

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FASTKD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 44

MIM #618855

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
High rate of hypomorphic variants as the cause of inherited ataxia and related diseases: study of a cohort of 366 families.
Benkirane M et al.·Genet Med
2021Cohort
Intermittent episodes of acute severe encephalomyopathy and early death in two siblings caused by biallelic likely pathogenic variants in FASTKD2: Expanding phenotype and literature review.
Kaur N et al.·Ann Hum Genet
2025Review
A novel homozygous missense mutation in the FASTKD2 gene leads to Lennox-Gastaut syndrome.
Wu T et al.·J Hum Genet
2022
Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency.
Wei X et al.·Hum Mutat
2020Case report
FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation.
Popow J et al.·RNA
2015
Homozygosity for a Rare FASTKD2 Variant Resulting in an Adult Onset Autosomal Recessive Mitochondrial Podocytopathy.
Gonçalves FP et al.·Am J Kidney Dis
2025Case report
[The study of mitochondrial disorder pedigree associated with FASTKD2 variants and uniparental disomy].
Ma YN et al.·Zhonghua Yi Xue Za Zhi
2023Case report
Identification of FASTKD2 compound heterozygous mutations as the underlying cause of autosomal recessive MELAS-like syndrome.
Yoo DH et al.·Mitochondrion
2017Case report
Dehydroepiandrosterone-induced changes in mitochondrial proteins contribute to phenotypic alterations in hepatoma cells.
Cheng ML et al.·Biochem Pharmacol
2016
Deciphering the RNA-binding protein interaction with the mRNAs encoded from human chromosome 15q11.2 BP1-BP2 microdeletion region.
Biswal SR et al.·Funct Integr Genomics
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools