MMS22L

Chr 6

MMS22 like, DNA repair protein

Also known as: C6orf167, dJ39B17.2

NCBI Gene: 253714ENSG00000146263UniProt: Q6ZRQ5

The protein encoded by this gene forms a complex with tonsoku-like, DNA repair protein (TONSL), and this complex recognizes and repairs DNA double-strand breaks at sites of stalled or collapsed replication forks. The encoded protein also can bind with the histone-associated protein NFKBIL2 to help regulate the chromatin state at stalled replication forks. Finally, this gene appears to be overexpressed in most lung and esophageal cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

177
ClinVar variants
16
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MMS22L
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 148 VUS of 177 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.44LOEUF
pLI 0.000
Z-score 5.36
OE 0.30 (0.21–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.29Z-score
OE missense 0.97 (0.90–1.03)
585 obs / 605.3 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.0.30 (0.21–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.90–1.03)
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.1.01
0≤1.21.6
LoF obs/exp: 21 / 69.0Missense obs/exp: 585 / 605.3Syn Z: -0.16

ClinVar Variant Classifications

177 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
VUS148
Likely Benign13
16
Pathogenic
148
VUS
13
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
0
0
0
VUS
0
145
3
0
148
Likely Benign
0
12
0
1
13
Benign
0
0
0
0
0
Total0157191177

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

View in ClinVar →

Protein Context — Lollipop Plot

MMS22L · 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
CRISPR screens reveal genetic determinants of PARP inhibitor sensitivity and resistance in prostate cancer.
Tsujino T et al.·Nat Commun
2023
Genes and Weightlifting Performance.
Kikuchi N et al.·Genes (Basel)
2021
Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis.
Nguyen MH et al.·Int J Oncol
2012
Discovery of a Recurrent Frameshift Ashkenazi Jewish Founder Mutation (F722fs) in the PARP Inhibitor-sensitive MMS22L Gene Associated with Higher Risk of Prostate Cancer.
Isaacs WB et al.·Eur Urol Focus
2025
A Tiered Approach to Exome Sequencing Analysis in Early-Onset Primary Ovarian Insufficiency.
McGlacken-Byrne SM et al.·J Clin Endocrinol Metab
2025
Toward a Multi-Trait Genetic Panel Targeting Training, Rehabilitation, and Chronic Disease Prevention: A Narrative Review.
Imperatore A et al.·Genes (Basel)
2025Review
A novel gene expression signature for bone metastasis in breast carcinomas.
Savci-Heijink CD et al.·Breast Cancer Res Treat
2016
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