ATPSCKMT

Chr 5

ATP synthase c subunit lysine N-methyltransferase

Also known as: FAM173B, JS-2, hFAM173B

NCBI Gene: 134145ENSG00000150756UniProt: Q6P4H8

Enables protein-lysine N-methyltransferase activity. Involved in several processes, including peptidyl-lysine trimethylation; positive regulation of proton-transporting ATP synthase activity, rotational mechanism; and positive regulation of sensory perception of pain. Located in mitochondrial crista. [provided by Alliance of Genome Resources, Jul 2025]

142
ClinVar variants
98
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ATPSCKMT
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 41 VUS of 142 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.
1.66LOEUF
pLI 0.000
Z-score -0.21
OE 1.06 (0.69–1.66)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.50Z-score
OE missense 1.12 (0.98–1.27)
161 obs / 144.2 exp
Tolerant

Tolerant to missense variation

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.1.06 (0.69–1.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (0.98–1.27)
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.0.92
0≤1.21.6
LoF obs/exp: 13 / 12.2Missense obs/exp: 161 / 144.2Syn Z: 0.45

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic98
VUS41
Likely Benign3
98
Pathogenic
41
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
98
0
98
Likely Pathogenic
0
0
0
0
0
VUS
0
37
4
0
41
Likely Benign
0
1
2
0
3
Benign
0
0
0
0
0
Total0381040142

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

View in ClinVar →

Protein Context — Lollipop Plot

ATPSCKMT · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain.
Willemen HLDM et al.·Cell Rep Med
2023
Lysine methylation by the mitochondrial methyltransferase FAM173B optimizes the function of mitochondrial ATP synthase.
Małecki JM et al.·J Biol Chem
2019
Expression of mitochondrial TSPO and FAM173B is associated with inflammation and symptoms in patients with painful knee osteoarthritis.
Palada V et al.·Rheumatology (Oxford)
2021Cohort
Identification of FAM173B as a protein methyltransferase promoting chronic pain.
Willemen HLDM et al.·PLoS Biol
2018
Human FAM173A is a mitochondrial lysine-specific methyltransferase that targets adenine nucleotide translocase and affects mitochondrial respiration.
Małecki JM et al.·J Biol Chem
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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