MTSS2

protein-coding

MTSS I-BAR domain containing 2, the group of I-BAR domain containing

Gene summary

Enables GTPase activator activity and small GTPase binding activity. Involved in activation of GTPase activity and cellular response to platelet-derived growth factor stimulus. Located in focal adhesion and ruffle membrane. Implicated in intellectual developmental disorder with ocular anomalies and distinctive facial features. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

MTSS1L

MANE transcript

NM_138383.3

Inheritance

ClinVar variants

P:2U:201B:51

Top phenotype

Intellectual developmental disorder with ocular anomalies and distinctive facial features

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr16:70,661,204-70,686,053

External References & Databases

Ensembl (ENSG00000132613)

Transcript & Mutation Effects

hg38 • Region Span ~24.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with ocular anomalies and distinctive facial featuresMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859303

Submitter: Ambry Genetics

intellectual developmental disorder with ocular anomalies and distinctive facial featuresSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859303

Submitter: PanelApp Australia

intellectual developmental disorder with ocular anomalies and distinctive facial featuresMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859303

Submitter: G2P

intellectual developmental disorder with ocular anomalies and distinctive facial featuresSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859303

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder with ocular anomalies and distinctive facial featuresAD

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 36067766

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTSS2 variants in ClinVar

11 Conditions Cataloged

not specifiedTotal: 178

not providedTotal: 70

Intellectual developmental disorder with ocular anomalies and distinctive facial featuresTotal: 15

MTSS2-related neurodevelopmental disorderTotal: 1

HypotoniaTotal: 1

Syndromic intellectual disabilityTotal: 1

Global developmental delayTotal: 1

MTSS1L-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138383.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	18 clinvar	1 clinvar	22
missense		2 clinvar	186 clinvar	31 clinvar	1 clinvar	220
nonsense			4 clinvar			4
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	2	201	49	2	254

Highest pathogenic variant AF is 0.00003539111

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138383.3	RefSeq	NP_612392.1	15	MANE Select
ENST00000338779.11	Ensembl	ENSP00000341171.6	15	MANE Select
ENST00000562883.6	Ensembl	ENSP00000455480.2	4	Standard
ENST00000576338.1	Ensembl	ENSP00000459654.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

plasma membrane organization
cellular response to platelet-derived growth factor stimulus
activation of GTPase activity
ruffle assembly
lamellipodium organization

Molecular Function

actin monomer binding
GTPase activator activity
phosphatidylinositol-4,5-bisphosphate binding
Rac GTPase binding

Cellular Component

lamellipodium
cortical actin cytoskeleton
ruffle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338779
Coding exons: 15
Length: 24863
Individuals with no LoFs: 125581
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125585
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.744	427	472	0.904	0.0000320	4675
Missense (PolyPhen)		159	197.45	0.80525		1842
Synonymous	-3.68	288	219	1.32	0.0000166	1588
Loss of Function	4.61	5	34.0	0.147	0.00000185	366

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000034	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in plasma membrane dynamics. Potentiated PDGF- mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation (PubMed:14752106). May function in actin bundling (PubMed:14752106). {ECO:0000269|PubMed:14752106}.;

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.102
RVIS EVS: -1.55
RVIS percentile EVS: 3.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.432

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium