MTSS1

Chr 8

MTSS I-BAR domain containing 1

Also known as: MIM, MIMA, MIMB

The MTSS1 protein binds actin monomers and regulates actin filament polymerization and bundling, playing important roles in cytoskeletal organization and cellular adhesion. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.21). Additional features may include renal abnormalities and bone mineralization defects based on the protein's predicted roles in kidney development and magnesium homeostasis.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
8
Pubs (1 yr)
54
P/LP submissions
0%
P/LP missense
0.21
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryMTSS1
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
54 unique Pathogenic / Likely Pathogenic· 116 VUS of 210 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 1.000
Z-score 5.14
OE 0.08 (0.040.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.81Z-score
OE missense 0.76 (0.700.83)
348 obs / 457.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.040.21)
00.351.4
Missense OE0.76 (0.700.83)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 3 / 36.5Missense obs/exp: 348 / 457.2Syn Z: 0.99
DN
0.4785th %ile
GOF
0.5072th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

210 submitted variants in ClinVar

Classification Summary

Pathogenic54
VUS116
Likely Benign7
Benign2
54
Pathogenic
116
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
54
0
54
Likely Pathogenic
0
0
0
0
0
VUS
0
110
6
0
116
Likely Benign
0
2
0
5
7
Benign
0
0
2
0
2
Total0112625179

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

View in ClinVar →

Protein Context — Lollipop Plot

MTSS1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC