AMOTL1

Summary

AMOTL1 (angiomotin like 1, HGNC:17811) is a protein-coding gene on chromosome 11q21, encoding Angiomotin-like protein 1 (Q8IY63). Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus.

The protein encoded by this gene is a peripheral membrane protein that is a component of tight junctions or TJs. TJs form an apical junctional structure and act to control paracellular permeability and maintain cell polarity. This protein is related to angiomotin, an angiostatin binding protein that regulates endothelial cell migration and capillary formation. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 154810 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Mendelian syndromes with cleft lip/palate (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 185 total — 8 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 110
• MANE Select transcript: NM_130847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17811
Approved symbol	AMOTL1
Name	angiomotin like 1
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	JEAP
Ensembl gene	ENSG00000166025
Ensembl biotype	protein_coding
OMIM	614657
Entrez	154810

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000299004, ENST00000317829, ENST00000433060, ENST00000537191, ENST00000539727, ENST00000892662, ENST00000892663, ENST00000920894, ENST00000957744

RefSeq mRNA: 2 — MANE Select: NM_130847 NM_001301007, NM_130847

CCDS: CCDS44712, CCDS73368

Canonical transcript exons

ENST00000433060 — 13 exons

Exon	Start	End
ENSE00001121768	94799390	94800311
ENSE00001257473	94850114	94850259
ENSE00001373823	94795011	94795160
ENSE00001532118	94831452	94831541
ENSE00001532124	94830050	94830194
ENSE00002217538	94870689	94876748
ENSE00002280481	94768356	94768560
ENSE00002455469	94853933	94854082
ENSE00002464353	94859525	94859715
ENSE00002501678	94864735	94864860
ENSE00002527751	94869198	94869473
ENSE00002532675	94865942	94866168
ENSE00003460512	94821530	94821821

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.0069 / max 435.1181, expressed in 1627 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116286	18.7297	1606
116285	1.3837	883
116274	1.2508	173
116275	0.3903	119
116277	0.3883	82
116287	0.3507	187
116273	0.1452	67
116276	0.1223	57
206419	0.0764	33
116272	0.0721	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	99.51	gold quality
deltoid	UBERON:0001476	98.88	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.21	gold quality
tendon of biceps brachii	UBERON:0008188	97.72	gold quality
body of tongue	UBERON:0011876	97.59	gold quality
tibia	UBERON:0000979	97.13	gold quality
quadriceps femoris	UBERON:0001377	97.11	gold quality
esophagus squamous epithelium	UBERON:0006920	97.05	gold quality
skeletal muscle tissue	UBERON:0001134	96.94	gold quality
vastus lateralis	UBERON:0001379	96.82	gold quality
upper arm skin	UBERON:0004263	96.82	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.64	gold quality
urethra	UBERON:0000057	96.51	gold quality
biceps brachii	UBERON:0001507	96.47	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.24	gold quality
gastrocnemius	UBERON:0001388	96.02	gold quality
secondary oocyte	CL:0000655	95.97	gold quality
muscle tissue	UBERON:0002385	95.90	gold quality
muscle of leg	UBERON:0001383	95.55	gold quality
saphenous vein	UBERON:0007318	95.48	gold quality
myocardium	UBERON:0002349	95.23	gold quality
left ventricle myocardium	UBERON:0006566	95.16	gold quality
tongue	UBERON:0001723	95.05	gold quality
nipple	UBERON:0002030	94.74	gold quality
upper leg skin	UBERON:0004262	94.60	gold quality
penis	UBERON:0000989	94.42	gold quality
mammalian vulva	UBERON:0000997	94.36	gold quality
visceral pleura	UBERON:0002401	94.22	gold quality
skin of hip	UBERON:0001554	93.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	8.60
E-GEOD-100618	no	286.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2

miRNA regulators (miRDB)

273 targeting AMOTL1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
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

Literature-anchored findings (GeneRIF, showing 18)

• The angiomotin-like 1 is involved in actin-cytoskeleton-based processes, in part, via its interaction with a p80-angiomotin-containing complex and the actin cytoskeleton (PMID:19565639)
• Amot and AmotL1 have similar effects on endothelial migration and tight junction formation in vitro. In vivo Amot appears to control the cell polarity and AmotL1 affects the stability of cell-cell junctions. (PMID:19590046)
• By yeast two-hybrid screening, angiomotin-like 1 (AmotL1) was identified as a host factor that interacts with the M protein of parainfluenza virus 5 (PIV5). (PMID:19932912)
• AmotL1 and ZO-2 are two candidates that could be harnessed to control the oncogenic function of YAP. (PMID:21685940)
• These results suggested that IFN-gamma exhibits anti-angiogenesis effects by regulating the expression of TNF-alpha-induced AmotL1 via NFkappaB in emphysema lungs. (PMID:23793505)
• Scaffold proteins angiomotin (Amot) and angiomotin-related AmotL1 and AmotL2 were recently identified as negative regulators of YAP and TAZ by preventing their nuclear translocation. (PMID:24003252)
• study defined eight additional recurrently mutated genes in SMZL; these genes are CREBBP, CBFA2T3, AMOTL1, FAT4, FBXO11, PLA2G4D, TRRAP and USH2A. (PMID:24349473)
• miR-124 binds AmotL1 3’UTR and down-regulates its expression repressing vasculogenic mimicry and cell motility in cervical cancer cells. (PMID:25218344)
• phosphorylation-deficient S793Ala mutant of AMOTL1 showed a shorter half-life and conferred resistance to energy-stress-induced YAP inhibition. (PMID:25373897)
• AMOTL1 Promotes Breast Cancer Progression and Is Antagonized by Merlin. (PMID:26806348)
• HECW2, a novel EC ubiquitin E3 ligase, plays a critical role in stabilizing endothelial cell-to-cell junctions by regulating AMOT-like 1 (AMOTL1) stability. (PMID:27498087)
• RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. (PMID:30531834)
• We found that AMOTL1 could link together parainfluenza virus 5 M proteins and NEDD4 family proteins. (PMID:30708959)
• AMOTL1 enhances YAP1 stability and promotes YAP1-driven gastric oncogenesis. (PMID:32313226)
• De novo variant in AMOTL1 in infant with cleft lip and palate, imperforate anus and dysmorphic features. (PMID:33026150)
• Angiomotin-like 1 plays a tumor-promoting role in glioma by enhancing the activation of YAP1 signaling. (PMID:34480788)
• A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature. (PMID:36751037)
• SRSF3/AMOTL1 splicing axis promotes the tumorigenesis of nasopharyngeal carcinoma through regulating the nucleus translocation of YAP1. (PMID:37558679)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Amotl1	ENSMUSG00000013076
rattus_norvegicus	Amotl1	ENSRNOG00000008990

Paralogs (2): AMOTL2 (ENSG00000114019), AMOT (ENSG00000126016)

Protein

Protein identifiers

Angiomotin-like protein 1 — Q8IY63 (reviewed: Q8IY63)

All UniProt accessions (2): Q8IY63, F8WDH4

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus.

Subcellular location. Cell junction. Tight junction.

Post-translational modifications. Polyubiquitinated by NEDD4, leading to proteasomal degradation.

Disease relevance. Craniofaciocardiohepatic syndrome (CFCHS) [MIM:621192] An autosomal dominant disorder characterized by orofacial clefting, congenital heart disease, tall stature, auricular anomalies, gastrointestinal manifestations, and developmental delay. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the angiomotin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IY63-1	1	yes
Q8IY63-2	2

RefSeq proteins (2): NP_001287936, NP_570899* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009114	Angiomotin	Family
IPR024646	Angiomotin_C	Domain
IPR051747	Angiomotin-like	Family

Pfam: PF12240

UniProt features (39 total): modified residue 10, sequence variant 9, region of interest 7, coiled-coil region 4, compositionally biased region 4, sequence conflict 2, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY63-F1	61.14	0.28

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): 241, 269, 295, 720, 793, 805, 828, 900, 902, 906

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2028269	Signaling by Hippo
R-HSA-162582	Signal Transduction

MSigDB gene sets: 151 (showing top): CREL_01, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, KEGG_TIGHT_JUNCTION, GOBP_HIPPO_SIGNALING, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, NFKB_Q6, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, NFKB_C, GOBP_BLOOD_VESSEL_MORPHOGENESIS, TGACATY_UNKNOWN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, AACTTT_UNKNOWN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, CUI_TCF21_TARGETS_2_DN, GOCC_CELL_CELL_JUNCTION

GO Biological Process (6): angiogenesis (GO:0001525), establishment of cell polarity involved in ameboidal cell migration (GO:0003365), Wnt signaling pathway (GO:0016055), actin cytoskeleton organization (GO:0030036), regulation of cell migration (GO:0030334), hippo signaling (GO:0035329)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), cytoplasmic vesicle (GO:0031410), COP9 signalosome (GO:0008180), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
ameboidal-type cell migration	1
establishment of cell polarity	1
cell surface receptor signaling pathway	1
cytoskeleton organization	1
actin filament-based process	1
cell migration	1
regulation of cell motility	1
intracellular signal transduction	1
protein binding	1
binding	1
cellular anatomical structure	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
intracellular vesicle	1
nuclear protein-containing complex	1
cell junction	1

Protein interactions and networks

STRING

1182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMOTL1	AKT1	P31749	986
AMOTL1	MYC	P01106	972
AMOTL1	STAT3	P40763	965
AMOTL1	YAP1	P46937	683
AMOTL1	WWC1	Q8IX03	636
AMOTL1	LATS1	O95835	632
AMOTL1	HECW2	Q9P2P5	627
AMOTL1	MPDZ	O75970	614
AMOTL1	NEDD4	P46934	613
AMOTL1	FAT4	Q6V0I7	593
AMOTL1	PATJ	Q8NI35	590
AMOTL1	PALS1	Q8N3R9	579
AMOTL1	AMOT	Q4VCS5	554
AMOTL1	LATS2	Q9NRM7	554
AMOTL1	PDPK1	O15530	551
AMOTL1	BAG3	O95817	551

IntAct

202 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
PALS1	LIN7A	psi-mi:“MI:0914”(association)	0.870
YAP1	MPDZ	psi-mi:“MI:0914”(association)	0.780
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
NF2	AMOTL1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AMOT	MPDZ	psi-mi:“MI:0914”(association)	0.670
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
AMOTL1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.610
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
AMOTL1	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.590
AMOTL1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.590
YAP1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
MAGEA4	MAGEB16	psi-mi:“MI:0914”(association)	0.530

BioGRID (158): AMOTL1 (Affinity Capture-RNA), AMOTL1 (Affinity Capture-RNA), AMOTL1 (Affinity Capture-RNA), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS), AMOTL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTY4, A2VD01, A5PMU4, A8E4V2, D2HNW6, E1BEQ5, O54972, O95644, P16236, P59281, P70365, P97305, Q12968, Q13191, Q13469, Q13905, Q15788, Q1LY51, Q2VPU4, Q3LRZ1, Q3TTA7, Q3U182, Q4PJW2, Q4VCS5, Q60591, Q61122, Q66IV1, Q68FF7, Q6DFR2, Q6GQL0, Q6NYU6, Q6ZNC4, Q80TM6, Q80VG1, Q8HWS3, Q8IXK0, Q8IY63, Q8K4S7, Q8N228, Q8VHG2

Diamond homologs: A0A8I3QA39, A1YB07, B8A5S6, E1BEQ5, F1MRK3, G3V735, Q4VCS5, Q8IY63, Q8K371, Q8VHG2, Q9D4H4, Q9Y2J4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AMPK	“up-regulates quantity by stabilization”	AMOTL1	phosphorylation
HECW2	“up-regulates activity”	AMOTL1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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
Signaling by Hippo	8	42.2×	2e-09
Ras activation upon Ca2+ influx through NMDA receptor	5	27.7×	5e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	26.4×	5e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	26.4×	5e-05
Dopamine Neurotransmitter Release Cycle	5	24.1×	7e-05
Long-term potentiation	5	23.1×	9e-05
Neurexins and neuroligins	12	22.9×	5e-11
Assembly and cell surface presentation of NMDA receptors	9	22.2×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	12	48.1×	4e-15
hippo signaling	8	40.4×	5e-09
protein localization to synapse	6	31.7×	3e-06
receptor clustering	7	30.1×	5e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	8	27.4×	1e-07
establishment of cell polarity	6	15.8×	2e-04
protein targeting	5	12.6×	2e-03
canonical NF-kappaB signal transduction	5	12.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	151
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1527654	GRCh37/hg19 11q14.1-22.1(chr11:77855209-98002445)	Pathogenic
1527655	GRCh37/hg19 11q14.1-21(chr11:80318996-96116221)	Pathogenic
1809349	GRCh37/hg19 11q14.1-22.3(chr11:81478509-104667040)x1	Pathogenic
2750552	NM_130847.3(AMOTL1):c.469C>T (p.Arg157Cys)	Pathogenic
3391915	GRCh37/hg19 11q14.1-22.1(chr11:81041448-98151664)x1	Pathogenic
3897539	NM_130847.3(AMOTL1):c.470G>A (p.Arg157His)	Pathogenic
3897540	NM_130847.3(AMOTL1):c.428A>G (p.Asn143Ser)	Pathogenic
3897541	NM_130847.3(AMOTL1):c.1735G>A (p.Glu579Lys)	Pathogenic
4071952	NM_130847.3(AMOTL1):c.475G>C (p.Glu159Gln)	Likely pathogenic

SpliceAI

2641 predictions. Top by Δscore:

Variant	Effect	Δscore
11:94795157:GTTG:G	donor_gain	1.0000
11:94799385:TTTA:T	acceptor_loss	1.0000
11:94799388:A:AG	acceptor_gain	1.0000
11:94799388:A:AT	acceptor_loss	1.0000
11:94799389:G:GA	acceptor_gain	1.0000
11:94799389:GTT:G	acceptor_gain	1.0000
11:94821818:CAAGG:C	donor_loss	1.0000
11:94821819:AAGG:A	donor_loss	1.0000
11:94821820:AGGTG:A	donor_loss	1.0000
11:94830045:TTTA:T	acceptor_loss	1.0000
11:94830048:A:AG	acceptor_gain	1.0000
11:94830049:G:GG	acceptor_gain	1.0000
11:94830049:G:GT	acceptor_loss	1.0000
11:94830049:GT:G	acceptor_gain	1.0000
11:94830049:GTTT:G	acceptor_gain	1.0000
11:94831448:ATAG:A	acceptor_loss	1.0000
11:94831449:TAG:T	acceptor_loss	1.0000
11:94831450:A:AG	acceptor_gain	1.0000
11:94831450:A:C	acceptor_loss	1.0000
11:94831451:G:GC	acceptor_loss	1.0000
11:94831451:G:GG	acceptor_gain	1.0000
11:94831537:CCAGA:C	donor_gain	1.0000
11:94831538:CAGA:C	donor_gain	1.0000
11:94831540:GA:G	donor_gain	1.0000
11:94831542:G:GG	donor_gain	1.0000
11:94850112:A:AG	acceptor_gain	1.0000
11:94850113:G:GG	acceptor_gain	1.0000
11:94850113:GAC:G	acceptor_gain	1.0000
11:94850256:GGAG:G	donor_gain	1.0000
11:94850257:GAG:G	donor_gain	1.0000

AlphaMissense

6271 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:94799761:T:C	Y191H	1.000
11:94799770:G:C	A194P	1.000
11:94799775:A:C	K195N	1.000
11:94799775:A:T	K195N	1.000
11:94830168:T:C	L511P	1.000
11:94830189:T:C	L518P	1.000
11:94853973:T:C	L612P	1.000
11:94853985:T:C	L616P	1.000
11:94853994:T:C	L619P	1.000
11:94854048:T:C	L637P	1.000
11:94859619:T:C	L680P	1.000
11:94859624:G:C	A682P	1.000
11:94859639:T:A	W687R	1.000
11:94859639:T:C	W687R	1.000
11:94859646:A:C	Q689P	1.000
11:94865953:T:C	L758P	1.000
11:94865958:G:C	A760P	1.000
11:94865979:G:C	A767P	1.000
11:94799495:T:C	L102P	0.999
11:94799761:T:G	Y191D	0.999
11:94799762:A:G	Y191C	0.999
11:94799771:C:A	A194D	0.999
11:94799773:A:G	K195E	0.999
11:94799774:A:T	K195I	0.999
11:94799782:T:C	S198P	0.999
11:94799948:T:C	L253P	0.999
11:94799963:T:A	V258D	0.999
11:94799972:T:A	L261H	0.999
11:94799972:T:C	L261P	0.999
11:94799974:A:C	S262R	0.999

dbSNP variants (sampled 300 via entrez): RS1000000062 (11:94706546 T>G), RS1000008670 (11:94749901 T>G), RS1000010273 (11:94872080 T>C), RS1000019012 (11:94748280 G>A), RS1000044312 (11:94793086 A>G), RS1000048938 (11:94830463 G>A), RS1000051035 (11:94755192 A>C), RS1000061222 (11:94750171 C>G), RS1000081294 (11:94796533 T>C), RS1000125793 (11:94821402 C>G,T), RS1000175563 (11:94787067 C>A,T), RS1000205793 (11:94866536 G>A,C), RS1000206712 (11:94787334 G>T), RS1000245601 (11:94790704 G>A), RS1000256990 (11:94872373 T>A)

Disease associations

OMIM: gene MIM:614657 | disease phenotypes: MIM:621192

GenCC curated gene-disease

Disease	Classification	Inheritance
Mendelian syndromes with cleft lip/palate	Strong	Autosomal dominant
orofacial cleft	Moderate	Autosomal dominant

Mondo (5): craniofaciocardiohepatic syndrome (MONDO:0978295), tethered spinal cord syndrome (MONDO:0006995), cleft lip/palate (MONDO:0016044), orofacial cleft (MONDO:0000358), (MONDO:0015335)

Orphanet (1): Cleft lip/palate (Orphanet:199306)

HPO phenotypes

110 total (30 of 110 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000076	Vesicoureteral reflux
HP:0000098	Tall stature
HP:0000126	Hydronephrosis
HP:0000143	Rectovaginal fistula
HP:0000162	Glossoptosis
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000308	Microretrognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000385	Small earlobe
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000411	Protruding ear
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000545	Myopia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000253_20	Attention deficit hyperactivity disorder and conduct disorder	2.000000e-06
GCST002929_11	Chromium levels	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
sodium arsenite	increases abundance, decreases expression, affects cotreatment	2
Cisplatin	affects cotreatment, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
tebuconazole	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	increases methylation	1
jinfukang	increases expression, affects cotreatment	1
mono(carboxy-isooctyl)phthalate	affects expression	1
Resveratrol	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04234971	PHASE4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	PHASE4	RECRUITING	Ketorolac in Palatoplasty
NCT03766217	PHASE3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	PHASE3	RECRUITING	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT00930124	PHASE2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT05591001	PHASE1	COMPLETED	Effects of Anesthetic Infusion on the Amplitude of Motor Evoked Potential in Pediatrics Undergoing Tethered Spinal Cord Surgeries
NCT04342234	Not specified	RECRUITING	Neural Network to Calculate Morphology of the Cleft Palate to Reduce Cleft Lip and Palate Treatment Burden.
NCT05867862	Not specified	COMPLETED	Implementation of a Program to Strengthen Oral Hygiene in Patient With Cleft Deformities
NCT06880094	Not specified	RECRUITING	Study of Congenital Orofacial Clefts by Implementing Optical Genome Mapping
NCT07340008	Not specified	RECRUITING	Analgosedation With Ketamine, Nalbuphine, or Dexmedetomidine for Suture Removal in Children After Cleft Surgery
NCT07557576	Not specified	RECRUITING	Effect of Opioid-Free vs Opioid-Based Anesthesia on Postoperative Pain and Emergence Agitation in Children Undergoing Cleft Surgery
NCT01382290	Not specified	WITHDRAWN	Magnetic Resonance Imaging of the Spine
NCT03702010	Not specified	COMPLETED	Spinal Cord Stimulation in Patients With Post-Laminectomy Syndrome in Testing Phase
NCT04189172	Not specified	ACTIVE_NOT_RECRUITING	MiDura-Study (Neuro-Patch in Duraplasty)
NCT04483570	Not specified	COMPLETED	Urological Deterioration in Secondary Tethered Cord Syndrome and Clue to Detect It
NCT05163899	Not specified	RECRUITING	Investigation of Surgical Sectioning of the Filum Terminale in Treating Occult Tethered Cord Syndrome Patients
NCT06408337	PHASE1/PHASE2	RECRUITING	Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00156442	Not specified	COMPLETED	A Study to Examine the Relationship Between Sleep Apnea and Cleft Lip/Palate
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01871623	Not specified	UNKNOWN	One-Piece Le Fort I Osteotomy Versus Segmental Le Fort I Osteotomy
NCT01932164	Not specified	COMPLETED	Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02789787	Not specified	COMPLETED	Clinical Effectiveness of Late Maxillary Protraction for Cleft Lip and Palate
NCT02845193	Not specified	COMPLETED	Effect of Novel Nasoalveolar Molding Techniques on Parents’ Satisfaction and Short Term Treatment Outcomes in Unilateral Cleft Lip and Palate Infants: A Randomized Controlled Trial
NCT02881606	Not specified	COMPLETED	Evaluation of the Clinical Effectiveness of Naso-alveolar Molding (NAM) Versus Computer Aided Design NAM (CAD/NAM) in Infants With Bilateral Cleft Lip and Palate: A Randomized Clinical Trial
NCT03011489	Not specified	UNKNOWN	Parent’s Satisfaction and Evaluation of Postsurgical Outcomes in Unilateral Cleft Lip / Palate Newly Born Infants With / Without Vacuum Formed Nasoalveolar Molding Aligners : A Controlled Clinical Trial
NCT03065686	Not specified	RECRUITING	Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing
NCT03165331	Not specified	UNKNOWN	Online Psychosocial Support for Young People With a Visible Difference: A Randomised Control Study
NCT03217890	Not specified	UNKNOWN	the Relationship Between Cleft Lip and / or Palate (Different Types) and ABO Blood Groups.
NCT03308266	Not specified	COMPLETED	Electromyographic Analysis of the Masticatory Muscles in Cleft Lip and Palate Children With Temporomandibular Disorders
NCT03395015	Not specified	COMPLETED	Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations
NCT03514563	Not specified	TERMINATED	Three Dimensional Facial Growth Analysis
NCT03563495	Not specified	COMPLETED	Tissue Engineered Constructs for Alveolar Cleft Repair
NCT03582111	Not specified	COMPLETED	Ultrasound Diagnosis of Cleft Lip and Palate
NCT03686761	Not specified	COMPLETED	Periodontal Changes Following Mid Maxillary Distraction
NCT03708406	Not specified	COMPLETED	Otologic and Rhinologic Outcomes in Children With Clef Palate
NCT03740841	Not specified	TERMINATED	Evaluation of the Effects of LUNII on Pre-operative Anxiety and on the Post-operative Period in Children With Cleft Lip and Palate Admitted for Alveolar Bone Graft: Pilot Study
NCT03750708	Not specified	WITHDRAWN	Oral Hygiene and Connected Toothbrush Before Alveolar Bone Graft for Cleft Lip and Palate
NCT03839290	Not specified	UNKNOWN	Development of the Palate in Bilateral Orofacial Cleft Newborns One Year After Early Neonatal Cheiloplasty