MTSS1

Chr 8

MTSS I-BAR domain containing 1

Also known as: MIM, MIMA, MIMB

NCBI Gene: 9788 ENSG00000170873 UniProt: O43312 OMIM: 608486

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in MTSS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 64

976 rare PASS variants

Rare truncating (LoF)

1 in 3,000

76 rare PASS variants

Rare synonymous (reference)

1 in 100

426 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MTSS1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 87	1 in 3,000
South Asian	~43k	1 in 62	1 in 1,100
Remaining (unassigned)	~30k	1 in 55	≈ 1 in 6,200
European (Finnish)	~27k	1 in 340	≈ 1 in 7,000
Admixed American	~22k	1 in 77	≈ 1 in 4,500
African / African American	~21k	1 in 62	1 in 2,500
East Asian	~20k	1 in 47	1 in 910
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 56	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 14 coding exons well covered in gnomAD exomes and genomes.? see exons ↓