TBX22

Summary

TBX22 (T-box transcription factor 22, HGNC:11600) is a protein-coding gene on chromosome Xq21.1, encoding T-box transcription factor TBX22 (Q9Y458). Probable transcriptional regulator involved in developmental processes. It is haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. Mutations in this gene have been associated with the inherited X-linked disorder, Cleft palate with ankyloglossia, and it is believed to play a major role in human palatogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 50945 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cleft palate with or without ankyloglossia, X-linked (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 174 total — 9 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 29
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001109878

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11600
Approved symbol	TBX22
Name	T-box transcription factor 22
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000122145
Ensembl biotype	protein_coding
OMIM	300307
Entrez	50945

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000373294, ENST00000373296, ENST00000476373, ENST00000626498, ENST00000626877, ENST00000924637, ENST00000968708

RefSeq mRNA: 4 — MANE Select: NM_001109878 NM_001109878, NM_001109879, NM_001303475, NM_016954

CCDS: CCDS14445

Canonical transcript exons

ENST00000373296 — 9 exons

Exon	Start	End
ENSE00003521240	80024063	80024164
ENSE00003760774	80026704	80026868
ENSE00003766113	80025603	80025777
ENSE00003766851	80027256	80027320
ENSE00003774600	80027991	80028076
ENSE00003844365	80030498	80031774
ENSE00003849958	80014753	80014887
ENSE00003890595	80023060	80023240
ENSE00003895265	80022268	80022444

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 87.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0394 / max 26.6140, expressed in 6 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196800	0.0275	5
196801	0.0067	1
209742	0.0051	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	87.93	gold quality
right testis	UBERON:0004534	87.86	gold quality
testis	UBERON:0000473	87.23	gold quality
right lobe of thyroid gland	UBERON:0001119	81.71	gold quality
left lobe of thyroid gland	UBERON:0001120	80.86	gold quality
thyroid gland	UBERON:0002046	79.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.09	gold quality
right atrium auricular region	UBERON:0006631	47.00	gold quality
descending thoracic aorta	UBERON:0002345	45.60	gold quality
popliteal artery	UBERON:0002250	43.87	gold quality
tibial artery	UBERON:0007610	43.81	gold quality
thoracic aorta	UBERON:0001515	43.72	gold quality
ascending aorta	UBERON:0001496	43.28	gold quality
ganglionic eminence	UBERON:0004023	41.02	silver quality
heart	UBERON:0000948	40.72	gold quality
cortical plate	UBERON:0005343	40.05	gold quality
apex of heart	UBERON:0002098	39.86	silver quality
prostate gland	UBERON:0002367	38.45	gold quality
heart left ventricle	UBERON:0002084	38.18	gold quality
endometrium	UBERON:0001295	38.13	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
left coronary artery	UBERON:0001626	37.08	silver quality
mucosa of stomach	UBERON:0001199	37.02	silver quality
skin of leg	UBERON:0001511	37.00	gold quality
skeletal muscle tissue	UBERON:0001134	36.39	gold quality
zone of skin	UBERON:0000014	36.25	gold quality
tibial nerve	UBERON:0001323	36.21	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skin of abdomen	UBERON:0001416	35.19	gold quality
saliva-secreting gland	UBERON:0001044	35.10	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
DLX5	Repression
INS
MSX2	Repression

Upstream regulators (CollecTRI, top): ETS1, MN1

miRNA regulators (miRDB)

58 targeting TBX22, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia (CPX) phenotype observed in CPX patients. (PMID:12374769)
• Four novel TBX22 splice site mutations in North American and Brazilian cleft palate families. (PMID:14729838)
• TBX22 is a target for the small ubiquitin-like modifier SUMO-1 and this modification is required for TBX22 repressor activity. (PMID:17846996)
• TBX22 mutations are responsible for a significant proportion of Thai non-syndromic cleft palate cases. (PMID:17868388)
• Analysis of the TBX22 promoter region revealed seven sequence variants, two of which are associated with cleft palate; this effect is stronger in a subgroup stratified for the presence of ankyloglossia. (PMID:19648124)
• 5 putative missense mutations were identified, 3 located in T-box binding domain (R120Q, R126W, and R151L) that affects DNA binding and/or transcriptional repression. 2 novel C-terminal mutations, P389Q and S400Y, did not affect TBX22 activity. (PMID:21248356)
• TBX22 is the gene underlying Abruzzo-Erickson syndrome. (PMID:22784330)
• These results suggest that a loss-of-function mutation in the X-linked TBX22 promoter may cause the cleft palate through disruption of TBX22-ETS-1 pathway. (PMID:25373698)
• we analysed two TBX22 promoter rs7055763 and rs41307258 single-nucleotide polymorphisms (SNPs) in 173 patients with NSCLP and 176 normal controls of south Indian origin using Kbioscience KASPar chemistry (PMID:25918826)
• Findings indicate the important role of T-box 22 protein (TBX22) in familial cases with X-linked cleft palate. (PMID:29932061)
• A Comprehensive Genetic Analysis of Slovenian Families with Multiple Cases of Orofacial Clefts Reveals Novel Variants in the Genes IRF6, GRHL3, and TBX22. (PMID:36901693)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tbx22	ENSMUSG00000031241
rattus_norvegicus	Tbx22	ENSRNOG00000002346
drosophila_melanogaster	H15	FBGN0016660
drosophila_melanogaster	mid	FBGN0261963
drosophila_melanogaster	ocm	FBGN0266083
caenorhabditis_elegans		WBGENE00003106
caenorhabditis_elegans		WBGENE00004750
caenorhabditis_elegans		WBGENE00006545
caenorhabditis_elegans		WBGENE00006546
caenorhabditis_elegans		WBGENE00006556
caenorhabditis_elegans		WBGENE00006557
caenorhabditis_elegans		WBGENE00006559
caenorhabditis_elegans		WBGENE00044798

Paralogs (16): TBX21 (ENSG00000073861), TBX5 (ENSG00000089225), TBX15 (ENSG00000092607), TBX18 (ENSG00000112837), TBX2 (ENSG00000121068), TBX4 (ENSG00000121075), TBX3 (ENSG00000135111), TBR1 (ENSG00000136535), TBX19 (ENSG00000143178), TBX6 (ENSG00000149922), EOMES (ENSG00000163508), TBXT (ENSG00000164458), TBX20 (ENSG00000164532), TBX10 (ENSG00000167800), MGA (ENSG00000174197), TBX1 (ENSG00000184058)

Protein

Protein identifiers

T-box transcription factor TBX22 — Q9Y458 (reviewed: Q9Y458)

All UniProt accessions (2): A0A0D9SGI2, Q9Y458

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcriptional regulator involved in developmental processes. This is major determinant crucial to palatogenesis.

Subcellular location. Nucleus.

Tissue specificity. Seems to be expressed at a low level.

Disease relevance. Cleft palate with or without ankyloglossia, X-linked (CPX) [MIM:303400] A congenital mouth abnormality characterized by fissure of the soft and/or hard palate, due to faulty fusion. Some patients also manifest ankyloglossia, a condition in which movements of the tongue are restricted. Complete ankyloglossia is due to fusion between the tongue and the floor of the mouth. Partial ankyloglossia is due to a short lingual frenum or one which is attached too near the tip of the tongue. The disease is caused by variants affecting the gene represented in this entry. Abruzzo-Erickson syndrome (ABERS) [MIM:302905] A disease characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y458-1	1	yes
Q9Y458-2	2

RefSeq proteins (4): NP_001103348, NP_001103349, NP_001290404, NP_058650 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001699	TF_T-box	Family
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR018186	TF_T-box_CS	Conserved_site
IPR036960	T-box_sf	Homologous_superfamily
IPR046360	T-box_DNA-bd	Domain

Pfam: PF00907

UniProt features (18 total): sequence variant 12, compositionally biased region 2, chain 1, DNA-binding region 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y458-F1	59.38	0.31

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 121 (showing top): GOBP_CELL_FATE_SPECIFICATION, GOBP_CELL_FATE_COMMITMENT, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MIKKELSEN_MEF_ICP_WITH_H3K27ME3, MIKKELSEN_ES_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, chrXq21, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR506_3P, MIR579_3P, MIR124_3P, MIR664B_3P, MIR5003_3P

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), cell fate specification (GO:0001708), regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	4
DNA-templated transcription	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
cell fate commitment	1
cellular developmental process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
nucleic acid binding	1
transcription regulator activity	1
binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

758 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBX22	CLPP	Q16740	994
TBX22	CLPX	O76031	961
TBX22	CLPS	P04118	940
TBX22	CLPB	Q9H078	868
TBX22	SP100	P23497	667
TBX22	MSX1	P28360	630
TBX22	IRF6	O14896	621
TBX22	BARX1	Q9HBU1	606
TBX22	SUMO1	P55856	600
TBX22	YME1L1	Q96TA2	594
TBX22	PAX9	P55771	523
TBX22	SHOX2	O60902	523
TBX22	MEOX2	P50222	519
TBX22	GRPEL1	Q9HAV7	507
TBX22	RNF168	Q8IYW5	490

IntAct

63 interactions, top by confidence:

A	B	Type	Score
VENTX	TBX22	psi-mi:“MI:0915”(physical association)	0.720
PITX2	TBX22	psi-mi:“MI:0915”(physical association)	0.560
YOD1	TBX22	psi-mi:“MI:0915”(physical association)	0.560
PROP1	TBX22	psi-mi:“MI:0915”(physical association)	0.560
TLX3	TBX22	psi-mi:“MI:0915”(physical association)	0.560
PITX1	TBX22	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	TBX22	psi-mi:“MI:0915”(physical association)	0.560
HTT	TBX22	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	TBX22	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	TBX22	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	TBX22	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (11): TBX22 (Two-hybrid), TBX22 (Reconstituted Complex), GOPC (Affinity Capture-MS), TBX22 (Two-hybrid), TBX22 (Two-hybrid), VENTX (Two-hybrid), TLX3 (Two-hybrid), PROP1 (Two-hybrid), GOPC (Affinity Capture-MS), APP (Reconstituted Complex), TBX22 (Affinity Capture-Luminescence)

ESM2 similar proteins: O13161, O15178, O60806, O70306, O75333, O95935, P20293, P24781, P56158, P57082, P70325, P70326, P79742, P79777, P79778, P79779, P87377, Q07998, Q17134, Q28HY0, Q29131, Q32NH9, Q3SA46, Q3SA47, Q3UPF5, Q5DTV4, Q5I2P1, Q5WM45, Q5XNS0, Q66JL1, Q810F8, Q861Q9, Q8AV66, Q8AXX2, Q8AYI2, Q8K402, Q91989, Q96SF7, Q98UD2, Q99593

Diamond homologs: A1YF56, A2AWL7, D3ZJK7, E1BEA8, O01409, O13161, O15119, O15178, O17212, O43435, O54839, O60806, O70306, O73718, O75333, O95935, O95936, O95947, P20293, P24781, P55965, P56158, P57082, P70323, P70324, P70325, P70326, P70327, P79742, P79777, P79778, P79779, P79944, P80492, P87377, P90971, Q07998, Q13207, Q16650, Q17134

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ETS1	“up-regulates quantity by expression”	TBX22	“transcriptional regulation”
TBX22	“down-regulates quantity by repression”	DLX5	“transcriptional regulation”
TBX22	“down-regulates quantity by repression”	MSX2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	6
Uncertain significance	74
Likely benign	19
Benign	21

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
11328	NM_001109878.2(TBX22):c.863+1G>C	Pathogenic
11329	NM_001109878.2(TBX22):c.779C>T (p.Thr260Met)	Pathogenic
11330	NM_001109878.2(TBX22):c.352G>T (p.Gly118Cys)	Pathogenic
11331	NM_001109878.2(TBX22):c.633+1G>A	Pathogenic
11332	NM_001109878.2(TBX22):c.667del (p.Arg223fs)	Pathogenic
11334	NM_001109878.2(TBX22):c.641T>C (p.Leu214Pro)	Pathogenic
11335	NM_001109878.2(TBX22):c.584_586dup (p.Ser195_Phe196insCys)	Pathogenic
11336	NM_001109878.2(TBX22):c.790A>T (p.Asn264Tyr)	Pathogenic
11337	NM_001109878.2(TBX22):c.1252del (p.Val418fs)	Pathogenic
11333	NM_001109878.2(TBX22):c.166G>T (p.Glu56Ter)	Likely pathogenic
1315207	NM_001109878.2(TBX22):c.766T>A (p.Phe256Ile)	Likely pathogenic
3065426	NM_001109878.2(TBX22):c.668G>A (p.Arg223Gln)	Likely pathogenic
3897167	NM_001109878.2(TBX22):c.358C>T (p.Arg120Trp)	Likely pathogenic
450864	NM_001109878.2(TBX22):c.899G>A (p.Trp300Ter)	Likely pathogenic
987387	NM_001109878.2(TBX22):c.458+1G>A	Likely pathogenic

SpliceAI

1358 predictions. Top by Δscore:

Variant	Effect	Δscore
X:80023211:GAC:G	donor_gain	1.0000
X:80024161:ATAG:A	donor_loss	1.0000
X:80024162:TAGG:T	donor_loss	1.0000
X:80024163:AG:A	donor_loss	1.0000
X:80024164:GG:G	donor_loss	1.0000
X:80024165:G:C	donor_loss	1.0000
X:80024166:T:C	donor_loss	1.0000
X:80025773:GCCAC:G	donor_gain	1.0000
X:80025778:G:GG	donor_gain	1.0000
X:80026703:GATC:G	acceptor_gain	1.0000
X:80028077:G:GG	donor_gain	1.0000
X:80014886:AGG:A	donor_loss	0.9900
X:80014887:GGTA:G	donor_loss	0.9900
X:80014888:G:T	donor_loss	0.9900
X:80022440:GCTTG:G	donor_gain	0.9900
X:80023188:TGGAA:T	donor_gain	0.9900
X:80023210:GGAC:G	donor_gain	0.9900
X:80023218:A:G	donor_gain	0.9900
X:80024057:TTACA:T	acceptor_loss	0.9900
X:80024058:TACA:T	acceptor_loss	0.9900
X:80024061:A:AC	acceptor_loss	0.9900
X:80024061:A:AG	acceptor_gain	0.9900
X:80024061:AGGC:A	acceptor_gain	0.9900
X:80024061:AGGCG:A	acceptor_gain	0.9900
X:80024062:G:GC	acceptor_loss	0.9900
X:80024062:G:GT	acceptor_gain	0.9900
X:80024062:GGC:G	acceptor_gain	0.9900
X:80024062:GGCG:G	acceptor_gain	0.9900
X:80024062:GGCGG:G	acceptor_gain	0.9900
X:80024158:GCTA:G	donor_gain	0.9900

AlphaMissense

3438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:80023197:T:C	F105L	0.997
X:80023199:C:A	F105L	0.997
X:80023199:C:G	F105L	0.997
X:80024070:T:C	F122L	0.996
X:80024072:C:A	F122L	0.996
X:80024072:C:G	F122L	0.996
X:80026738:G:C	R223P	0.995
X:80026836:T:C	F256L	0.995
X:80026837:T:C	F256S	0.995
X:80026838:C:A	F256L	0.995
X:80026838:C:G	F256L	0.995
X:80027270:A:C	K271N	0.994
X:80027270:A:T	K271N	0.994
X:80023188:T:A	W102R	0.993
X:80023188:T:C	W102R	0.993
X:80023198:T:C	F105S	0.993
X:80027266:T:C	L270P	0.993
X:80025625:T:A	W161R	0.992
X:80025625:T:C	W161R	0.992
X:80027298:T:C	F281L	0.992
X:80027300:T:A	F281L	0.992
X:80027300:T:G	F281L	0.992
X:80023190:G:C	W102C	0.991
X:80023190:G:T	W102C	0.991
X:80025627:G:C	W161C	0.991
X:80025627:G:T	W161C	0.991
X:80026711:T:C	L214P	0.991
X:80024071:T:G	F122C	0.990
X:80024074:C:A	P123H	0.990
X:80024118:T:G	Y138D	0.990

dbSNP variants (sampled 300 via entrez): RS1000993689 (X:80019046 TAGA>T), RS1001057237 (X:80029045 G>A,T), RS1001141387 (X:80029592 GT>G), RS1001557253 (X:80017362 C>T), RS1001575943 (X:80013977 T>C), RS1001633015 (X:80025477 T>G), RS1001691583 (X:80023373 C>G), RS1001923834 (X:80018586 T>C), RS1001968109 (X:80027498 C>G,T), RS1001974818 (X:80021676 C>T), RS1002061478 (X:80027131 T>G), RS1002090342 (X:80031979 C>A), RS1002294041 (X:80018999 A>G), RS1002733843 (X:80023097 C>T), RS1002965591 (X:80015425 C>A)

Disease associations

OMIM: gene MIM:300307 | disease phenotypes: MIM:303400, MIM:302905, MIM:119530

GenCC curated gene-disease

Disease	Classification	Inheritance
cleft palate with or without ankyloglossia, X-linked	Definitive	X-linked
Abruzzo-Erickson syndrome	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
cleft palate with or without ankyloglossia, X-linked	Definitive	XL

Mondo (4): cleft palate with or without ankyloglossia, X-linked (MONDO:0010560), Abruzzo-Erickson syndrome (MONDO:0010554), orofacial cleft (MONDO:0000358), cleft palate (MONDO:0016064)

Orphanet (4): X-linked cleft palate and ankyloglossia (Orphanet:324601), Abruzzo-Erickson syndrome (Orphanet:921), Orofacial clefting syndrome (Orphanet:139039), Cleft palate (Orphanet:2014)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000174	Abnormal palate morphology
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000567	Chorioretinal coloboma
HP:0000589	Coloboma
HP:0000612	Iris coloboma
HP:0001156	Brachydactyly
HP:0001417	X-linked inheritance
HP:0001631	Atrial septal defect
HP:0001770	Toe syndactyly
HP:0001831	Short toe
HP:0002974	Radioulnar synostosis
HP:0004322	Short stature
HP:0008743	Coronal hypospadias
HP:0009465	Ulnar deviation of finger
HP:0010296	Ankyloglossia
HP:0010751	Dimple chin
HP:0012368	Flat face
HP:0100542	Abnormal localization of kidney

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003999_20	Nose size	2.000000e-07

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
C535559	Abruzzo Erickson syndrome (supp.)
C536426	Cleft palate X-linked (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Demecolcine	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Vincristine	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT00760006	PHASE2	COMPLETED	Preventing Complications in Cleft Palate Repair With Antibiotics
NCT01760330	PHASE2	WITHDRAWN	IV Acetaminophen in Children Undergoing Palatoplasty
NCT02350803	PHASE2	COMPLETED	Does Use of Rigid Fixation After Removing Distraction Osteogenesis Device Reduce the Relapse?
NCT03412474	PHASE2	COMPLETED	Suprazygomatic Block in Cleft Palate Surgery in Children
NCT03157076	Not specified	COMPLETED	Pilot Study to Investigate the Creation of Physiological Rhythm by Closed Loop Stimulation in hEart Failure pAtients With chronoTropic incompEtence
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
NCT01616953	PHASE1/PHASE2	COMPLETED	Cell Therapy for Craniofacial Bone Defects
NCT02247193	PHASE1/PHASE2	COMPLETED	Botulinum Toxin to Improve Cosmesis of Primary Cleft Lip Repair
NCT00097149	Not specified	COMPLETED	Systematic Pediatric Care for Oral Clefts - South America
NCT00285714	Not specified	UNKNOWN	3D Imaging of Hard and Soft Tissue in Orthognathic Surgery
NCT00340977	Not specified	COMPLETED	Svangerskap, Arv, Og Miljo (Pregnancy, Heredity and Environment)
NCT00423072	Not specified	COMPLETED	Middle Ear Pressure Disregulation in Cleft Palate Patients
NCT00584272	Not specified	COMPLETED	Retrospective Study on the Outcome of Cleft Palate Repair: Comparing US Surgical and Ethicon Suture Materials
NCT00773994	Not specified	COMPLETED	Pilot Study Evaluating Characteristic Closure Patterns of the Normal Velopharyngeal Portal
NCT00779961	Not specified	UNKNOWN	An Investigation for the Optimal Timing of a Cleft Palate Repair
NCT00829101	Not specified	COMPLETED	Articulation and Phonology in Children With Unilateral Cleft Lip and Palate
NCT00993551	Not specified	COMPLETED	Timing of Primary Surgery for Cleft Palate
NCT00993993	Not specified	COMPLETED	Relational Development in Children With Cleft Lips and Palates: Influence of the Waiting Period Prior to the First Surgical Intervention and the Parents’ Psychological Perception of the Abnormality
NCT01046591	Not specified	COMPLETED	Sleep and Behavior in Children With Cleft Palate
NCT01252264	Not specified	COMPLETED	FaceBase Biorepository
NCT01380171	Not specified	COMPLETED	Primary Palatoplasty in Pediatric Patients - A Retrospective Review of Surgical Outcomes
NCT01500109	Not specified	COMPLETED	Efficacy of Oral Versus Intravenous Acetaminophen for Primary Pediatric Cleft Palate Repair
NCT01535131	Not specified	COMPLETED	Furlow Palatoplasty With Tensor Tenopexy
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01867632	Not specified	COMPLETED	Acellular Dermal Matrix in Primary Palatoplasty
NCT02329509	Not specified	COMPLETED	Evaluation of Facial Growth in Two Primary Protocols Used in the Surgical Treatment of Unilateral Cleft Lip and Palate Patients