MTSS2

Summary

MTSS2 (MTSS I-BAR domain containing 2, HGNC:25094) is a protein-coding gene on chromosome 16q22.1, encoding Protein MTSS 2 (Q765P7). Involved in plasma membrane dynamics.

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 ruffle membrane. Implicated in intellectual developmental disorder with ocular anomalies and distinctive facial features.

Source: NCBI Gene 92154 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with ocular anomalies and distinctive facial features (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 247 total — 1 likely-pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_138383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25094
Approved symbol	MTSS2
Name	MTSS I-BAR domain containing 2
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	ABBA-1, LOC92154, ABBA
Ensembl gene	ENSG00000132613
Ensembl biotype	protein_coding
OMIM	616951
Entrez	92154

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000338779, ENST00000562883, ENST00000576338

RefSeq mRNA: 1 — MANE Select: NM_138383 NM_138383

CCDS: CCDS32476

Canonical transcript exons

ENST00000338779 — 15 exons

Exon	Start	End
ENSE00000904669	70677792	70677899
ENSE00000904670	70678252	70678409
ENSE00000904671	70679630	70679704
ENSE00001366390	70665466	70665540
ENSE00001368468	70664920	70665096
ENSE00001416432	70676881	70676978
ENSE00001419482	70674306	70674528
ENSE00001424190	70679971	70680055
ENSE00001504181	70664598	70664763
ENSE00001625202	70679786	70679877
ENSE00001630105	70680794	70680867
ENSE00001673309	70680964	70681025
ENSE00002258409	70685723	70686053
ENSE00002431533	70679315	70679323
ENSE00002603332	70661204	70664449

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.9488 / max 1133.7410, expressed in 1574 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157971	41.8207	1566
157963	1.5412	657
157970	1.4488	804
157950	0.6469	302
157960	0.4923	240
157949	0.3313	164
157962	0.2833	138
157959	0.2746	141
157968	0.2702	161
207936	0.2646	131

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.00	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.55	gold quality
sural nerve	UBERON:0015488	98.53	gold quality
right frontal lobe	UBERON:0002810	98.35	gold quality
cerebellar hemisphere	UBERON:0002245	98.32	gold quality
cerebellar cortex	UBERON:0002129	98.26	gold quality
ventricular zone	UBERON:0003053	97.90	gold quality
amygdala	UBERON:0001876	97.72	gold quality
anterior cingulate cortex	UBERON:0009835	97.49	gold quality
cingulate cortex	UBERON:0003027	97.39	gold quality
spinal cord	UBERON:0002240	97.34	gold quality
nucleus accumbens	UBERON:0001882	97.19	gold quality
stromal cell of endometrium	CL:0002255	96.93	gold quality
cortical plate	UBERON:0005343	96.88	gold quality
ganglionic eminence	UBERON:0004023	96.52	gold quality
prefrontal cortex	UBERON:0000451	96.43	gold quality
cerebellum	UBERON:0002037	96.11	gold quality
caudate nucleus	UBERON:0001873	96.02	gold quality
popliteal artery	UBERON:0002250	95.64	gold quality
mucosa of stomach	UBERON:0001199	95.62	gold quality
tibial artery	UBERON:0007610	95.62	gold quality
body of uterus	UBERON:0009853	95.51	gold quality
putamen	UBERON:0001874	95.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.08	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.07	gold quality
right lobe of liver	UBERON:0001114	94.99	gold quality
lower esophagus	UBERON:0013473	94.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.95	gold quality
right coronary artery	UBERON:0001625	94.56	gold quality
endocervix	UBERON:0000458	94.54	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting MTSS2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-92A-2-5P	99.75	67.01	2164

Literature-anchored findings (GeneRIF, showing 3)

• these data indicates that the interaction between full-length Abba and Rac1 is implicated in membrane deformation and subjected to a growth factor-mediated regulation through the C-terminal sequence. (PMID:20875796)
• The ABBA motif in cyclin A is required for its proper degradation in prometaphase through competing with BUBR1 for the same site on CDC20 (PMID:25669885)
• The recurrent de novo c.2011C>T missense variant in MTSS2 causes syndromic intellectual disability. (PMID:36067766)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mtss1la	ENSDARG00000028943
danio_rerio	mtss1lb	ENSDARG00000087260
mus_musculus	Mtss2	ENSMUSG00000033763
rattus_norvegicus	Mtss2	ENSRNOG00000017500
caenorhabditis_elegans	M04F3.5	WBGENE00019771

Paralogs (1): MTSS1 (ENSG00000170873)

Protein

Protein identifiers

Protein MTSS 2 — Q765P7 (reviewed: Q765P7)

Alternative names: Actin-bundling with BAIAP2 homology protein 1, MTSS1-like protein

All UniProt accessions (3): Q765P7, H3BPV0, I3L2G4

UniProt curated annotations — full annotation on UniProt →

Function. Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation. May function in actin bundling.

Subunit / interactions. Interacts (via IMD domain) with RAC1; this interaction may be important to potentiate PDGF-induced RAC1 activation.

Subcellular location. Cytoplasm. Cell projection. Ruffle.

Disease relevance. Intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF) [MIM:620086] An autosomal dominant disorder characterized by global developmental delay, mild intellectual disability, ophthalmologic anomalies, microcephaly or relative microcephaly, hearing loss, and characteristic facial features including long, upslanting palpebral fissures, bitemporal narrowing of the forehead, arched eyebrows, and epicanthal folds. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the MTSS family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q765P7-1	1	yes
Q765P7-2	2

RefSeq proteins (1): NP_612392* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003124	WH2_dom	Domain
IPR013606	I-BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR030127	MTSS1/MTSS2	Family

Pfam: PF02205, PF08397

UniProt features (46 total): mutagenesis site 13, modified residue 10, compositionally biased region 9, region of interest 6, splice variant 3, domain 2, chain 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q765P7-F1	62.75	0.32

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 260, 264, 441, 579, 601, 612, 624, 634, 639, 643

Mutagenesis-validated functional residues (13):

Position	Phenotype
115	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
116	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
123	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
127	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
130	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
137	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
138	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
139	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
145	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
148	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
149	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
152	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf
157	marked reduction in rac1-binding, loss of increase in rac1 activity and of dorsal ruffles formation in response to pdgf

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): chr16q22, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOCC_RUFFLE, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_RESPONSE_TO_PLATELET_DERIVED_GROWTH_FACTOR, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, ABBUD_LIF_SIGNALING_1_DN, GOBP_LAMELLIPODIUM_ORGANIZATION, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOMF_ACTIN_BINDING

GO Biological Process (6): plasma membrane organization (GO:0007009), cell projection assembly (GO:0030031), cellular response to platelet-derived growth factor stimulus (GO:0036120), membrane organization (GO:0061024), activation of GTPase activity (GO:0090630), lamellipodium organization (GO:0097581)

GO Molecular Function (7): actin binding (GO:0003779), actin monomer binding (GO:0003785), GTPase activator activity (GO:0005096), phospholipid binding (GO:0005543), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasmic side of plasma membrane (GO:0009898), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), cortical actin cytoskeleton (GO:0030864), ruffle membrane (GO:0032587), ruffle (GO:0001726), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell leading edge	2
plasma membrane bounded cell projection	2
cellular anatomical structure	2
endomembrane system organization	1
membrane organization	1
cellular component assembly	1
cell projection organization	1
response to platelet-derived growth factor	1
cellular response to growth factor stimulus	1
cellular component organization	1
positive regulation of GTPase activity	1
plasma membrane bounded cell projection organization	1
cytoskeletal protein binding	1
actin binding	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
lipid binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
GTPase binding	1
binding	1
plasma membrane	1
cytoplasmic side of membrane	1
cytoskeleton	1
actin cytoskeleton	1
cortical cytoskeleton	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTSS2	BAIAP2L2	Q6UXY1	583
MTSS2	VAC14	Q08AM6	539
MTSS2	BAIAP2L1	Q9UHR4	538
MTSS2	ARHGEF37	A1IGU5	461
MTSS2	EPS8L3	Q8TE67	452
MTSS2	FCHSD1	Q86WN1	449
MTSS2	UNC80	Q8N2C7	438
MTSS2	COG4	Q9H9E3	408
MTSS2	PTPRQ	Q9UMZ3	405
MTSS2	KCNG1	Q9UIX4	398
MTSS2	SF3B3	Q15393	396
MTSS2	AMPD2	Q01433	396
MTSS2	DNMBP	Q6XZF7	394
MTSS2	FBXL12	Q9NXK8	391
MTSS2	ARHGAP4	P98171	383
MTSS2	LRRC10	Q5BKY1	383

IntAct

19 interactions, top by confidence:

A	B	Type	Score
ALAS1	MTSS2	psi-mi:“MI:0915”(physical association)	0.560
MTSS2	SCAF1	psi-mi:“MI:0915”(physical association)	0.560
GIGYF1	DYNC1I1	psi-mi:“MI:0914”(association)	0.350
ACTB	ENAH	psi-mi:“MI:0914”(association)	0.350
BCL9L	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MTSS2	CHEK1	psi-mi:“MI:0914”(association)	0.350
EPHA7	PIK3R2	psi-mi:“MI:2364”(proximity)	0.270
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270
MTSS2	ALAS1	psi-mi:“MI:0915”(physical association)	0.000
SCAF1	MTSS2	psi-mi:“MI:0915”(physical association)	0.000
	MTSS2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (48): MTSS1L (Affinity Capture-MS), MTSS1L (Affinity Capture-MS), MTSS1L (Affinity Capture-MS), MTSS1L (Two-hybrid), MTSS1L (Two-hybrid), MTSS1L (Proximity Label-MS), ATF1 (Affinity Capture-MS), OTUD7B (Affinity Capture-MS), MTSS1 (Affinity Capture-MS), GFER (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), CNN2 (Affinity Capture-MS), AMMECR1L (Affinity Capture-MS), GCA (Affinity Capture-MS), MIS18A (Affinity Capture-MS)

ESM2 similar proteins: A1A5B6, A6H7I8, A7E300, B9VTT2, F1LXF1, M0R7T9, O08873, O14795, O60347, O60447, P0C6S7, P11274, P22681, P22682, P49797, Q0IHY4, Q0VGY8, Q14432, Q3MII6, Q4KUS2, Q5CD77, Q62769, Q69ZT9, Q6A039, Q6F6B3, Q6P9S0, Q6PAJ1, Q6PCS4, Q6ZM89, Q765P7, Q80U28, Q80YA9, Q8BIZ1, Q8CGA2, Q8K214, Q8R1S4, Q8WXG6, Q8WXI2, Q923Q2, Q92625

Diamond homologs: O43312, Q6P9S0, Q765P7, Q8R1S4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	276.6×	2e-14
Activation of BAD and translocation to mitochondria	6	268.7×	2e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	237.1×	3e-12
Activation of BH3-only proteins	6	175.2×	2e-11
RHO GTPases activate PKNs	6	112.0×	2e-10
Intrinsic Pathway for Apoptosis	6	103.3×	4e-10
FOXO-mediated transcription	5	98.8×	2e-08
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	63.5×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	6	33.0×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

247 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	187
Likely benign	34
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
183351	NM_138383.3(MTSS2):c.1790C>T (p.Thr597Met)	Likely pathogenic

SpliceAI

2404 predictions. Top by Δscore:

Variant	Effect	Δscore
16:70664447:AGCCT:A	acceptor_loss	1.0000
16:70664448:GCC:G	acceptor_loss	1.0000
16:70664450:C:CC	acceptor_gain	1.0000
16:70664450:CTGGG:C	acceptor_loss	1.0000
16:70664451:T:C	acceptor_loss	1.0000
16:70664615:T:TA	donor_gain	1.0000
16:70664759:CCGTG:C	acceptor_gain	1.0000
16:70664760:CGTGC:C	acceptor_gain	1.0000
16:70664762:TG:T	acceptor_gain	1.0000
16:70664763:GCT:G	acceptor_loss	1.0000
16:70664764:C:CC	acceptor_gain	1.0000
16:70664764:CTG:C	acceptor_loss	1.0000
16:70664918:AC:A	donor_loss	1.0000
16:70664919:C:A	donor_loss	1.0000
16:70665092:CAGTC:C	acceptor_gain	1.0000
16:70665093:AGTC:A	acceptor_gain	1.0000
16:70665094:GTC:G	acceptor_gain	1.0000
16:70665094:GTCC:G	acceptor_loss	1.0000
16:70665095:TC:T	acceptor_gain	1.0000
16:70665095:TCC:T	acceptor_loss	1.0000
16:70665096:CC:C	acceptor_gain	1.0000
16:70665097:C:CA	acceptor_loss	1.0000
16:70665097:C:CC	acceptor_gain	1.0000
16:70665098:T:G	acceptor_loss	1.0000
16:70665590:A:T	acceptor_gain	1.0000
16:70676876:CTGA:C	donor_loss	1.0000
16:70676877:TGAC:T	donor_loss	1.0000
16:70676878:GAC:G	donor_loss	1.0000
16:70676879:A:AT	donor_loss	1.0000
16:70676880:C:CA	donor_loss	1.0000

AlphaMissense

4805 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:70663741:A:G	I727T	1.000
16:70663741:A:T	I727N	1.000
16:70664225:G:T	R566S	1.000
16:70664228:G:T	R565S	1.000
16:70664230:A:C	I564S	1.000
16:70664230:A:G	I564T	1.000
16:70664230:A:T	I564N	1.000
16:70664656:G:C	S471R	1.000
16:70664656:G:T	S471R	1.000
16:70664658:T:G	S471R	1.000
16:70664717:A:G	L451P	1.000
16:70676965:A:G	L249P	1.000
16:70677798:G:C	S242R	1.000
16:70677798:G:T	S242R	1.000
16:70677800:T:G	S242R	1.000
16:70677862:A:G	L221P	1.000
16:70677880:A:G	L215P	1.000
16:70678265:A:G	L204P	1.000
16:70678289:C:G	R196P	1.000
16:70678295:C:G	R194P	1.000
16:70678307:A:G	L190P	1.000
16:70678311:C:G	A189P	1.000
16:70678316:C:G	R187P	1.000
16:70678323:C:G	A185P	1.000
16:70678343:A:G	L178P	1.000
16:70679645:T:C	K148E	1.000
16:70679650:A:G	L146P	1.000
16:70679654:T:C	K145E	1.000
16:70679669:A:G	S140P	1.000
16:70679676:T:A	K137N	1.000

dbSNP variants (sampled 300 via entrez): RS1000114854 (16:70674054 TA>T,TAA), RS1000120297 (16:70669554 G>A), RS1000153430 (16:70687105 T>C), RS1000252289 (16:70674254 G>A), RS1000331878 (16:70662544 G>A), RS1000339476 (16:70678950 CAAGA>C), RS1000348016 (16:70680819 C>G), RS1000368519 (16:70683646 G>GC), RS1000435809 (16:70663791 T>C,G), RS1000485613 (16:70666621 T>C), RS1000554000 (16:70685998 GGCGGCGCGGGGGGC>G,GGCGGCGCGGGGGGCGCGGCGCGGGGGGC), RS1000648585 (16:70683481 G>C,T), RS1000672393 (16:70671170 C>T), RS1000817071 (16:70676789 G>A,C), RS1000877107 (16:70679144 ACCCCGGGGG>A)

Disease associations

OMIM: gene MIM:616951 | disease phenotypes: MIM:620086

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with ocular anomalies and distinctive facial features	Strong	Autosomal dominant

Mondo (4): intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), intellectual developmental disorder with ocular anomalies and distinctive facial features (MONDO:0859303), syndromic intellectual disability (MONDO:0000508)

Orphanet (2): Rare genetic syndromic intellectual disability (Orphanet:183763), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000341	Narrow forehead
HP:0000407	Sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000729	Autistic behavior
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0003593	Infantile onset
HP:0007750	Hypoplasia of the fovea
HP:0011523	Iris cyst

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005553_1	Diffuse cutaneous systemic sclerosis	1.000000e-06
GCST006993_12	Hippocampal volume in Alzheimer’s disease dementia	1.000000e-07
GCST010703_100	Brain morphology (MOSTest)	2.000000e-40
GCST010725_47	Malaria	6.000000e-07
GCST012214_1	Alzheimer’s disease	9.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation, affects cotreatment	4
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Cadmium	decreases expression, increases abundance, increases expression	2
Estradiol	decreases expression, increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	increases expression, affects expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects expression	1
ethyl-p-hydroxybenzoate	increases expression	1
butyraldehyde	decreases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
polyhexamethyleneguanidine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Ampicillin	increases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1

Clinical trials (associated diseases)

211 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders