MTSS1

Chr 8

MTSS I-BAR domain containing 1

Also known as: MIM, MIMA, MIMB

NCBI Gene: 9788 ENSG00000170873 UniProt: O43312

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.

ResearchSummary from RefSeq, UniProt

Enables actin monomer binding activity; identical protein binding activity; and signaling receptor binding activity. Predicted to be involved in several processes, including adherens junction maintenance; positive regulation of actin filament bundle assembly; and renal tubule development. Predicted to act upstream of or within several processes, including actin filament polymerization; bone mineralization; and magnesium ion homeostasis. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.21

Clinical Summary— MTSS1

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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.

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ClinVar Variants

110 VUS of 151 total submissions

Explore recent and relevant literature in Research Assistant →

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?

0.21LOEUF

pLI 1.000

Z-score 5.14

OE 0.08 (0.04–0.21)

Highly constrained

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

Missense Constraint?

1.81Z-score

OE missense 0.76 (0.70–0.83)

348 obs / 457.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.21)

0≤0.351.4

Missense OE?0.76 (0.70–0.83)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 3 / 36.5Missense obs/exp: 348 / 457.2Syn Z: 0.99

This gene — mechanism propensity

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

151 submitted variants in ClinVar

ClinVar

Classification Summary

VUS110

Likely Benign8

Benign2

110

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	110	0	0	110
Likely Benign	3	0	5	8
Benign	0	2	0	2
Total	113	2	5	120

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

View in ClinVar →

54 pathogenic / likely-pathogenic (of 61) ClinVar copy-number / structural variants overlap MTSS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →