MKLN1

Chr 7

muskelin 1

Also known as: TWA2

NCBI Gene: 4289ENSG00000128585UniProt: Q9UL63

Muskelin is an intracellular protein that acts as a mediator of cell spreading and cytoskeletal responses to the extracellular matrix component thrombospondin I (MIM 188060) (Adams et al., 1998 [PubMed 9724633]).[supplied by OMIM, Mar 2008]

80
ClinVar variants
27
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MKLN1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 53 VUS of 80 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.17LOEUF
pLI 1.000
Z-score 5.75
OE 0.07 (0.03–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.74Z-score
OE missense 0.61 (0.54–0.68)
232 obs / 383.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.07 (0.03–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.54–0.68)
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.0.83
0≤1.21.6
LoF obs/exp: 3 / 44.2Missense obs/exp: 232 / 383.0Syn Z: 1.50

ClinVar Variant Classifications

80 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS53
26
Pathogenic
1
Likely Pathogenic
53
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
1
0
1
VUS
0
46
7
0
53
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04634080

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

View in ClinVar →

Protein Context — Lollipop Plot

MKLN1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Long non‑coding RNA MKLN1‑AS aggravates hepatocellular carcinoma progression by functioning as a molecular sponge for miR‑654‑3p, thereby promoting hepatoma‑derived growth factor expression.
Gao W et al.·Int J Mol Med
2020
Constructed Risk Prognosis Model Associated with Disulfidptosis lncRNAs in HCC.
Jia X et al.·Int J Mol Sci
2023Functional
Prognostic analysis of hepatocellular carcinoma based on cuproptosis -associated lncRNAs.
Wei M et al.·BMC Gastroenterol
2024
Ferroptosis-related lncRNA signature predicts the prognosis and immune microenvironment of hepatocellular carcinoma.
Fang C et al.·Sci Rep
2022
A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility.
Liu Y et al.·Sci Rep
2024
Prognostic Signature Constructed of Seven Ferroptosis-Related lncRNAs Predicts the Prognosis of HBV-Related HCC.
Wang W et al.·J Gastrointest Cancer
2024
A prognostic signature based on the expression profile of the ferroptosis-related long non-coding RNAs in hepatocellular carcinoma.
Lin X et al.·Adv Clin Exp Med
2022
Genome-Wide Association Study for Resting Electrocardiogram in the Qatari Population Identifies 6 Novel Genes and Validates Novel Polygenic Risk Scores.
Khan N et al.·J Am Heart Assoc
2025
Identification of a CD4+ conventional T cells-related lncRNAs signature associated with hepatocellular carcinoma prognosis, therapy, and tumor microenvironment.
Zhu L et al.·Front Immunol
2023
Identification of a Novel Eight-lncRNA Prognostic Signature for HBV-HCC and Analysis of Their Functions Based on Coexpression and ceRNA Networks.
Zhao X et al.·Biomed Res Int
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The CTLH ubiquitin ligase substrates ZMYND19 and MKLN1 negatively regulate mTORC1 at the lysosomal membrane.
Wang Y et al.·Nat Commun
2025🔓 Open Access
MKLN1-dependent GID4/CTLH E3 ubiquitin ligase complex assemblies are required to support B-cell antibody diversification.
Barbulescu P et al.·J Immunol
2025🔓 Open Access
Identification of MMP14 and MKLN1 as colorectal cancer susceptibility genes and drug-repositioning candidates from a genome-wide association study.
Yun D et al.·J Transl Med
2025🔓 Open Access
LncRNA MKLN1-AS promotes glioma tumorigenesis and growth via activating the Hippo pathway through miR-126-5p/TEAD1 axis.
Chen S et al.·Naunyn Schmiedebergs Arch Pharmacol
2025
Molecular mechanism of RB progression and Circ_0082415 inhibits MKLN1 translation to suppress retinoblastoma progression: Changes in mRNA and protein levels.
Ning Y et al.·Int J Biol Macromol
2025Functional
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