AFDN

Summary

AFDN (afadin, adherens junction formation factor, HGNC:7137) is a protein-coding gene on chromosome 6q27, encoding Afadin (P55196). Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs).

This gene encodes a multi-domain protein involved in signaling and organization of cell junctions during embryogenesis. It has also been identified as the fusion partner of acute lymphoblastic leukemia (ALL-1) gene, involved in acute myeloid leukemias with t(6;11)(q27;q23) translocation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, however, not all have been fully characterized.

Source: NCBI Gene 4301 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cleft lip/palate (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 119 total — 29 pathogenic, 2 likely-pathogenic
• Regional missense constraint (gnomAD): 3 of 8 regions constrained (≈3% of expected missense variation)
• GTEx eGene: eQTL in 30 tissues, sQTL in 13 (q < 0.05)
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.40 (moderately constrained)
• MANE Select transcript: NM_001386888
• Interaction hub: 1,884 STRING partners (top 9% of genes corpus-wide)
• Notable: 119 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7137
Approved symbol	AFDN
Name	afadin, adherens junction formation factor
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	AF-6, AF6
Ensembl gene	ENSG00000130396
Ensembl biotype	protein_coding
OMIM	159559
Entrez	4301

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 21 protein_coding, 5 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000683244

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 5, TSL 3: 3, TSL 4: 2, TSL 5: 7

ENST00000683244, ENST00000344191, ENST00000351017, ENST00000366806, ENST00000366809, ENST00000392108, ENST00000392112, ENST00000400822, ENST00000400824, ENST00000400825, ENST00000423229, ENST00000447894, ENST00000476946, ENST00000485634, ENST00000486649, ENST00000497596, ENST00000503021, ENST00000507679, ENST00000507704, ENST00000509296, ENST00000511503, ENST00000511637, ENST00000515794, ENST00000913561, ENST00000913562, ENST00000913563, ENST00000913564, ENST00001141773

RefSeq mRNA: 8 — MANE Select: NM_001386888 NM_001040000, NM_001207008, NM_001291964, NM_001366319, NM_001366320, NM_001366321, NM_001386888, NM_001410951

CCDS: CCDS47517, CCDS75553, CCDS78199, CCDS94033, CCDS94034, CCDS94035

Canonical transcript exons

ENST00000683244 — 34 exons

Exon	Start	End
ENSE00001010034	167893862	167893906
ENSE00001750508	167872214	167872377
ENSE00002438520	167965757	167966045
ENSE00002690486	167962433	167962567
ENSE00003514287	167969114	167969198
ENSE00003922122	167826911	167827237
ENSE00003978622	167947853	167947944
ENSE00003978623	167896878	167896972
ENSE00003978624	167943941	167944059
ENSE00003978625	167911284	167911489
ENSE00003978626	167925005	167925091
ENSE00003978627	167948293	167948478
ENSE00003978628	167875335	167875495
ENSE00003978629	167914644	167914738
ENSE00003978630	167911101	167911162
ENSE00003978631	167889215	167889326
ENSE00003978632	167864551	167864746
ENSE00003978633	167890862	167891029
ENSE00003978635	167898205	167898467
ENSE00003978636	167917089	167917232
ENSE00003978637	167902317	167902386
ENSE00003978638	167943402	167943475
ENSE00003978639	167907171	167907289
ENSE00003978640	167915168	167915433
ENSE00003978641	167880360	167880517
ENSE00003978642	167922856	167922959
ENSE00003978643	167913403	167913423
ENSE00003978644	167914168	167914313
ENSE00003978645	167946707	167946901
ENSE00003978646	167918735	167918933
ENSE00003978647	167870386	167870498
ENSE00003978648	167943129	167943194
ENSE00003978649	167951186	167952187
ENSE00004799593	167969782	167972023

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1917 / max 162.7461, expressed in 1650 samples.

Highest expression (Bgee): uterine tube, sural nerve, lower esophagus mucosa, cortical plate, bronchial epithelial cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AFDN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	8.3e-55	+0.68	6:167706443:G:A
Artery Tibial	eqtl	3.5e-21	+0.31	6:167827812:G:C
Adipose Subcutaneous	sqtl	2.5e-18	-0.43	6:167935400:G:A
Skin Sun Exposed Lower leg	eqtl	1.5e-16	+0.17	6:167962003:G:T
Muscle Skeletal	sqtl	3.3e-16	-0.41	6:167935400:G:A
Adipose Subcutaneous	eqtl	3.3e-15	+0.47	6:167842555:GTA:G
Esophagus Muscularis	eqtl	9.0e-13	+0.26	6:167911944:C:T
Adipose Visceral Omentum	sqtl	1.0e-12	-0.43	6:167935400:G:A
Thyroid	eqtl	1.4e-12	+0.15	6:167920700:T:C
Artery Aorta	eqtl	3.6e-10	+0.25	6:167884022:T:C
Esophagus Mucosa	eqtl	1.8e-09	-0.10	6:167695966:T:G
Colon Sigmoid	eqtl	5.3e-09	+0.23	6:167911944:C:T
Skin Not Sun Exposed Suprapubic	eqtl	8.0e-09	+0.14	6:167911861:T:C
Pancreas	eqtl	3.2e-08	+0.21	6:167961602:GTGT:G
Testis	eqtl	1.6e-07	+0.10	6:167870188:A:G
Muscle Skeletal	eqtl	1.8e-07	-0.31	6:167947459:T:G
Breast Mammary Tissue	eqtl	3.8e-07	-0.34	6:167832333:C:T
Esophagus Gastroesophageal Junction	eqtl	4.1e-06	+0.22	6:167839605:T:C
Adipose Visceral Omentum	eqtl	8.0e-06	-0.27	6:167947709:C:T
Adrenal Gland	eqtl	8.9e-06	+0.33	6:167912686:G:A

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
71214	10.9158	1622
71215	0.7961	517
71212	0.1223	62
71233	0.1188	57
71224	0.1042	38
71232	0.0721	39
71213	0.0262	9
71223	0.0238	14
71231	0.0088	4
71230	0.0036	2

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.38	gold quality
sural nerve	UBERON:0015488	98.92	gold quality
lower esophagus mucosa	UBERON:0035834	98.70	gold quality
cortical plate	UBERON:0005343	98.48	gold quality
bronchial epithelial cell	CL:0002328	98.45	gold quality
ganglionic eminence	UBERON:0004023	98.02	gold quality
right lung	UBERON:0002167	97.97	gold quality
buccal mucosa cell	CL:0002336	97.94	gold quality
minor salivary gland	UBERON:0001830	97.82	gold quality
body of pancreas	UBERON:0001150	97.68	gold quality
rectum	UBERON:0001052	97.61	gold quality
esophagus mucosa	UBERON:0002469	97.57	gold quality
caput epididymis	UBERON:0004358	97.48	gold quality
jejunal mucosa	UBERON:0000399	97.43	gold quality
esophagus squamous epithelium	UBERON:0006920	97.42	gold quality
amniotic fluid	UBERON:0000173	97.36	gold quality
calcaneal tendon	UBERON:0003701	97.36	gold quality
mouth mucosa	UBERON:0003729	97.33	gold quality
oral cavity	UBERON:0000167	97.29	gold quality
saliva-secreting gland	UBERON:0001044	97.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.12	gold quality
skin of leg	UBERON:0001511	96.98	gold quality
skin of abdomen	UBERON:0001416	96.89	gold quality
left lobe of thyroid gland	UBERON:0001120	96.88	gold quality
upper lobe of left lung	UBERON:0008952	96.85	gold quality
colonic epithelium	UBERON:0000397	96.75	gold quality
upper lobe of lung	UBERON:0008948	96.73	gold quality
right lobe of thyroid gland	UBERON:0001119	96.68	gold quality
vagina	UBERON:0000996	96.57	gold quality
thyroid gland	UBERON:0002046	96.53	gold quality
upper leg skin	UBERON:0004262	96.53	gold quality
ventricular zone	UBERON:0003053	96.42	gold quality
pituitary gland	UBERON:0000007	96.24	gold quality
adenohypophysis	UBERON:0002196	96.21	gold quality
transverse colon	UBERON:0001157	96.16	gold quality
esophagus	UBERON:0001043	96.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.08	gold quality
metanephros cortex	UBERON:0010533	95.99	gold quality
pharyngeal mucosa	UBERON:0000355	95.89	gold quality
body of stomach	UBERON:0001161	95.85	gold quality
mucosa of stomach	UBERON:0001199	95.85	gold quality
peritoneum	UBERON:0002358	95.75	gold quality
omental fat pad	UBERON:0010414	95.75	gold quality
epithelium of nasopharynx	UBERON:0001951	95.73	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.69	gold quality
right lobe of liver	UBERON:0001114	95.60	gold quality
stomach	UBERON:0000945	95.54	gold quality
endometrium	UBERON:0001295	95.51	gold quality
left ovary	UBERON:0002119	95.46	gold quality
pancreas	UBERON:0001264	95.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.44	gold quality
skin of hip	UBERON:0001554	95.34	gold quality
apex of heart	UBERON:0002098	95.34	gold quality
zone of skin	UBERON:0000014	95.33	gold quality
tibia	UBERON:0000979	95.29	gold quality
tibial nerve	UBERON:0001323	95.16	gold quality
small intestine	UBERON:0002108	95.15	gold quality
tendon	UBERON:0000043	95.13	gold quality
body of uterus	UBERON:0009853	95.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.01	gold quality
islet of Langerhans	UBERON:0000006	94.99	gold quality
germinal epithelium of ovary	UBERON:0001304	94.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.97	gold quality
sigmoid colon	UBERON:0001159	94.80	gold quality
ectocervix	UBERON:0012249	94.78	gold quality
intestine	UBERON:0000160	94.77	gold quality
gall bladder	UBERON:0002110	94.72	gold quality
lower lobe of lung	UBERON:0008949	94.71	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.67	gold quality
ovary	UBERON:0000992	94.66	gold quality
corpus epididymis	UBERON:0004359	94.64	gold quality
large intestine	UBERON:0000059	94.56	gold quality
colon	UBERON:0001155	94.53	gold quality
colonic mucosa	UBERON:0000317	94.50	gold quality
lower esophagus	UBERON:0013473	94.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.45	gold quality
fundus of stomach	UBERON:0001160	94.44	gold quality
right ovary	UBERON:0002118	94.39	gold quality
tendon of biceps brachii	UBERON:0008188	94.38	gold quality
gingiva	UBERON:0001828	94.31	gold quality
left uterine tube	UBERON:0001303	94.28	gold quality
seminal vesicle	UBERON:0000998	94.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.11	gold quality
parotid gland	UBERON:0001831	94.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.97	gold quality
gingival epithelium	UBERON:0001949	93.88	gold quality
right testis	UBERON:0004534	93.85	gold quality
left testis	UBERON:0004533	93.78	gold quality
duodenum	UBERON:0002114	93.77	gold quality
adipose tissue	UBERON:0001013	93.74	gold quality
tonsil	UBERON:0002372	93.68	gold quality
heart left ventricle	UBERON:0002084	93.66	gold quality
female reproductive system	UBERON:0000474	93.64	gold quality
endocervix	UBERON:0000458	93.63	gold quality
cardiac ventricle	UBERON:0002082	93.54	gold quality
renal medulla	UBERON:0000362	93.46	gold quality
mammary duct	UBERON:0001765	93.44	gold quality
connective tissue	UBERON:0002384	93.42	gold quality
right atrium auricular region	UBERON:0006631	93.39	gold quality
testis	UBERON:0000473	93.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	17.13
E-ANND-3	yes	14.42

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Choroid plexus	tissue	108.7
Locus coeruleus	tissue	91.1
Hippocampus	tissue	86.5	low
Postcentral gyrus	tissue	84.7
Nucleus accumbens	tissue	74.6
Esophagus	tissue	57.6	medium
Small intestine	tissue	48.8	medium
Salivary gland	tissue	47.2	medium
Liver	tissue	46.0	medium
Fallopian tube	tissue	42.1	medium
Lung	tissue	39.6	low
Rectum	tissue	39.3	medium
Vagina	tissue	39.2	medium
Superior colliculi	tissue	38.3
Pancreas	tissue	37.4	medium
Hypothalamus	tissue	37.0
Breast	tissue	36.7	medium
Thalamus	tissue	36.7
Retina	tissue	36.0
Cerebellum	tissue	35.8	medium
Colon	tissue	35.2	medium
Stomach 1	tissue	34.9	high
Duodenum	tissue	34.1	medium
Pons	tissue	33.7
Pituitary gland	tissue	33.1
Thyroid gland	tissue	32.6	medium
Skin 1	tissue	32.2	medium
Prostate	tissue	32.0	medium
Midbrain	tissue	31.8
Placenta	tissue	31.7	medium
Medulla oblongata	tissue	31.1
Substantia nigra	tissue	30.9
Kidney	tissue	30.2	medium
Hippocampal formation	tissue	30.2
Periaqueductal gray	tissue	29.6
Cerebral cortex	tissue	29.4	low
Motor cortex	tissue	29.4
Prefrontal cortex	tissue	29.2
Epididymis	tissue	29.2	medium
Spinal cord	tissue	28.5
Insular cortex	tissue	27.9
Somatosensory cortex	tissue	27.8
Retrosplenial cortex	tissue	27.4
Skeletal muscle	tissue	27.3	medium
Entorhinal cortex	tissue	27.3
Adipose tissue	tissue	27.2	not detected
Retrosplenial and cingulate cortex	tissue	26.6
Corpus callosum	tissue	26.5
Endometrium 1	tissue	26.4	medium
Amygdala	tissue	26.3
Septum	tissue	26.1
Temporal cortex	tissue	25.8
Occipital cortex	tissue	25.5
Caudate putamen	tissue	24.9
Ventral forebrain	tissue	24.5
Parathyroid gland	tissue	24.2	medium
Spleen	tissue	24.2	not detected
Testis	tissue	23.7	medium
Tongue	tissue	23.6
Frontal cortex	tissue	22.7

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Parieto-temporal junction (white matter) (109.9), Globus pallidus, internus (109.4), Temporal white matter (108.5), Nucleus ambiguus (108.4), Subthalamic nucleus (107.2).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.398, missense Z 1.9 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000683244 splits into 8 regions with different missense tolerance; 3 are missense-constrained (≈3% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
6:167,827,133–167,864,553	81 / 51.2	1.58	no
6:167,864,554–167,864,602	4 / 18.7	0.21	yes (p 6.8e-04)
6:167,864,603–167,915,366	817 / 965.7	0.85	no
6:167,915,367–167,915,425	5 / 23.4	0.21	yes (p 1.4e-04)
6:167,915,426–167,922,953	162 / 182.6	0.89	no
6:167,922,954–167,925,091	12 / 35.6	0.34	yes (p 7.8e-05)
6:167,943,129–167,944,038	74 / 98.8	0.75	no
6:167,944,039–167,969,932	981 / 966.0	1.02	no

Literature-anchored findings (GeneRIF, showing 34)

• RYK, a catalytically inactive receptor tyrosine kinase, associates with EphB2 and EphB3 but does not interact with AF-6. (PMID:11956217)
• Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain (PMID:12808105)
• Results report the solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr. (PMID:15684424)
• AF6 negatively regulates Rap1-induced cell adhesion. (PMID:16051602)
• In the Acute Myeloid Leukemia patients, detected MLL rearrangements consisting of MLL/AF6, MLL/AF9, MLL/AF17 , MLL/ELL and MLL partial tandem duplication. MLL rearrangement include chromosome translocation and partial tandem duplication. (PMID:16086288)
• Loss of afadin is associated with breast cancer (PMID:16819513)
• AF6/s-afadin is a candidate for mediating control of cellular growth processes by regulated translocation to the nucleus. (PMID:17013812)
• c-Src is recruited by AF-6 to cell-cell contact sites, suggesting that c-Src is regulated by a PDZ protein in special cellular locations. (PMID:17491594)
• AF6 protein is important for spreading of Herpes simplex virus 1 in epithelial cells (PMID:17967423)
• two distal surfaces of the AF-6 PDZ domain respond differently to peptide binding; distal surface 1 changes in millisecond dynamics, whereas distal surface 2 undergoes structural rearrangement (PMID:18052198)
• JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates beta1 integrin levels and cell migration. (PMID:19176753)
• Results demonstrate a novel molecular mechanism by which Rap1 and afadin regulate the VEGF- and S1P-induced angiogenesis. (PMID:20413783)
• The interaction between the PDZ domain of afadin (AF6_PDZ) and a series of polypeptides comprising the PDZ-binding motif, was studied. (PMID:20586101)
• AF6/afadin is a marker of poor outcome in breast cancer, and its loss induces cell migration, invasiveness and tumor growth (PMID:21478912)
• Results demonstrate a role for afadin in the regulation of vascular barrier function via coordination of adherens junction-tight junction and p120-catenin-ZO-1 interactions. (PMID:21732359)
• the Necl-5-nectin, nectin-nectin, and nectin-afadin interactions cooperatively increase the clustering of the nectin-afadin complex at the cell-cell contact sites, promoting the formation of the nectin-based cell-cell adhesion. (PMID:21880730)
• AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson’s disease. (PMID:23393160)
• JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton. (PMID:23885123)
• The expression levels of CFTR and AF-6/afadin are significantly downregulated in human colon cancer tissues. (PMID:24373847)
• MLL-AF6 oncoprotein potentiates the activity of the RAS pathway through retention of AF6 within the nucleus. (PMID:24695851)
• AF-6/afadin could be a useful selection marker for fertility-sparing therapy for patients with atypical hyperplasia or grade 1 endometrioid adenocarcinoma with no myometrial invasion. (PMID:25879875)
• In pancreatic cancer cells, AF6 is expressed at reduced levels, causing Dvl2 to be upregulated and available to bind and enhance FOXE1-induced trans-activation of Snail, which promotes proliferation and metastasis. (PMID:26013125)
• miR-188-3p is a novel independent prognostic factor in colorectal cancer patients, which can be partly explained by its effect on MLLT4 expression and migration of cancer cells. (PMID:27601590)
• Afadin (AFDN), a cytoskeletal and junction-associated protein, was present in 2D and 3D keratinocyte cultures, and validated as a so-far-unknown EphA2-interacting protein. (PMID:27815408)
• AF6 employs a non-canonical, evolutionarily conserved alpha-helix to bind RAS, unique to AF6 and the classical RASSF effectors. (PMID:29062045)
• CLDN6 enhances the chemoresistance to ADM via activating the AF-6/ERK signaling pathway and up-regulating cancer stem cell characters in MDAMB231 cells. (PMID:29159771)
• high levels of both Claudin-2 and Afadin in primary tumors were associated with poor disease-specific survival, relapse-free survival, lung-specific relapse, and liver-specific relapse (PMID:30692208)
• The authors report here that the homophilic receptor PTPRK is stabilized at cell-cell contacts in epithelial cells. PTPRK directly and selectively dephosphorylates at least five substrates, including Afadin, PARD3 and delta-catenin family members, which are all important cell-cell adhesion regulators. (PMID:30924770)
• Afadin binding with interaction partners in adipocytes, among which HDAC6 preferentially interacts with phosphorylated Afadin and acts as a key intermediate to suppress insulin receptor protein levels. (PMID:31264358)
• Afadin (AF6) in cancer progression: A multidomain scaffold protein with complex and contradictory roles. (PMID:33165933)
• Proximity proteomics identifies PAK4 as a component of Afadin-Nectin junctions. (PMID:34493720)
• [Clinical characteristics and prognosis of MLL-AF6 positive patients with acute myeloid leukemia]. (PMID:34650294)
• Damaging Mutations in AFDN Contribute to Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate. (PMID:36384317)
• This paper deals with AF-6 in mouse, rat, and cow. (PMID:9722616)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	afdna	ENSDARG00000029472
mus_musculus	Afdn	ENSMUSG00000068036
rattus_norvegicus	Afdn	ENSRNOG00000023753
drosophila_melanogaster	cno	FBGN0259212
caenorhabditis_elegans	afd-1	WBGENE00021009

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1314653) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 62 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal ectoderm development	2
abnormal mesoderm development	2
abnormal neural tube morphology	2
absent allantois	2
abnormal embryonic neuroepithelium morphology	2
abnormal synapse morphology	2
embryonic lethality during organogenesis, complete penetrance	2
abnormal cecum morphology	1
abnormal urinary bladder morphology	1
abnormal liver morphology	1
enlarged liver	1
abnormal spleen morphology	1
enlarged spleen	1
small spleen	1
enlarged lymph nodes	1
abnormal nervous system tract morphology	1
abnormal cerebral cortex morphology	1
abnormal cerebral cortex lamination	1
abnormal hippocampus morphology	1
absent notochord	1
abnormal telencephalon development	1
abnormal uterus morphology	1
abnormal germ layer development	1
abnormal somite development	1
decreased embryo size	1

+37 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	Q5IS48	96.1%	Diamond
Oryctolagus cuniculus	O19132	94.1%	Diamond
Xenopus laevis	P51142	92.9%	Diamond
Xenopus tropicalis	Q05AS8	92.9%	Diamond
Canis lupus familiaris	E2QYC9	85.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KIF25-AS1	ncRNA	100505879
KIF25	protein-coding	3834
AFDN-DT	ncRNA	653483
LINC01558	ncRNA	26238
LINC02487	ncRNA	441178
HGC6.3	ncRNA	100128124

Protein

Protein identifiers

Afadin — P55196 (reviewed: P55196)

Alternative names: ALL1-fused gene from chromosome 6 protein, Afadin adherens junction formation factor

All UniProt accessions (13): A0A804HJ20, A8MQ02, E9PFY5, P55196, F8W9I4, H0Y7R8, H0Y8L4, H0Y8U8, H0Y948, H0Y9I0, H0YA98, J3KN01, Q5TIG5

UniProt curated annotations — full annotation on UniProt →

Function. Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton. May play a key role in the organization of epithelial structures of the embryonic ectoderm. Essential for the organization of adherens junctions.

Subunit / interactions. Homodimer. Interacts with F-actin, nectin and NECTIN3. Essential for the association of nectin and E-cadherin. Isoform 1/s-afadin does not interact with F-actin. Interacts with ZO-1 and occludin, but probably in an indirect manner. Interacts with RIT1 and RIT2. Interacts with NRXN1 and BCR. Interacts with ADAM10; the interaction locks ADAM10 at adherens junctions following ADAM10 recruitment to adherens junctions by TSPAN33.

Subcellular location. Cell junction. Adherens junction.

Disease relevance. A chromosomal aberration involving AFDN is associated with acute leukemias. Translocation t(6;11)(q27;q23) with KMT2A/MLL1. The result is a rogue activator protein.

Domain organisation. The PDZ/DHR domain interacts with the C-terminus of nectin and the Pro-rich C-terminal domain interacts with F-actin.

Miscellaneous. May be due to intron retention. May be due to intron retention.

Isoforms (6)

UniProt ID	Names	Canonical?
P55196-4	4	yes
P55196-2	1, s-afadin
P55196-1	2, l-afadin
P55196-3	3
P55196-6	6
P55196-5	5

RefSeq proteins (8): NP_001035089, NP_001193937, NP_001278893, NP_001353248, NP_001353249, NP_001353250, NP_001373817, NP_001397880 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000253	FHA_dom	Domain
IPR001478	PDZ	Domain
IPR002710	Dilute_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR028842	Afadin	Family
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR037977	CBD_Afadin	Domain
IPR060075	AFDN_dom	Domain

Pfam: PF00498, PF00595, PF00788, PF01843, PF26705

UniProt features (98 total): modified residue 33, compositionally biased region 21, splice variant 11, strand 8, region of interest 7, domain 5, coiled-coil region 3, sequence conflict 3, helix 3, turn 2, chain 1, site 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
7QCR	MLLT4/Afadin PDZ domain in complex with the C-terminal peptide from protein E of …	X-RAY DIFFRACTION	2.28
5A6C	Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation	X-RAY DIFFRACTION	2.9
1T2M	Solution Structure Of The Pdz Domain Of AF-6	SOLUTION NMR
1XZ9	Structure of AF-6 PDZ domain	SOLUTION NMR
2AIN	Solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide from the …	SOLUTION NMR
2EXG	Making Protein-Protein Interactions Drugable: Discovery of Low-Molecular-Weight Ligands …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55196-F1	63.69	0.25

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cell junctions; plasma membrane; nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

Functional residue map

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

Catalytic / active sites (1)

Position	Role
26	breakpoint for translocation to form kmt2a/mll1-afdn

Post-translational modifications (33)

Type	Positions
Phosphoserine	216, 246, 256, 391, 424, 512, 557, 562, 589, 655, 1083, 1107, 1126, 1140, 1143, 1172, 1173, 1182, 1199, 1238, 1275, 1328, 1501, 1512, 1696, 1721, 1774, 1779, 1799
Phosphothreonine	1211, 1232, 1330
N6-acetyllysine	1807

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 1; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

1 pathways:

ID	Pathway	Evidence
R-HSA-418990	Adherens junctions interactions	electronic

MSigDB gene sets: 256 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_BCELL_DN, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_ENDOTHELIAL_INTESTINAL_BARRIER, GOBP_REGULATION_OF_CELL_CELL_ADHESION_MEDIATED_BY_CADHERIN, GOBP_APICAL_JUNCTION_ASSEMBLY, KEGG_TIGHT_JUNCTION, GOMF_GTPASE_BINDING, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CELL_CELL_ADHESION, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN

GO Biological Process (16): cell adhesion (GO:0007155), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of gene expression (GO:0010628), positive regulation of cell-cell adhesion (GO:0022409), negative regulation of cell migration (GO:0030336), regulation of protein localization (GO:0032880), cell-cell adhesion mediated by cadherin (GO:0044331), pore complex assembly (GO:0046931), establishment of protein localization to plasma membrane (GO:0061951), bicellular tight junction assembly (GO:0070830), establishment of endothelial intestinal barrier (GO:0090557), positive regulation of cell-cell adhesion mediated by cadherin (GO:2000049), cell differentiation (GO:0030154), cell junction organization (GO:0034330), adherens junction maintenance (GO:0034334)

GO Molecular Function (5): small GTPase binding (GO:0031267), cadherin binding (GO:0045296), cell adhesion molecule binding (GO:0050839), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (10): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), cell junction (GO:0030054), cell-cell contact zone (GO:0044291), pore complex (GO:0046930), tight junction (GO:0070160), cytoplasm (GO:0005737)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Cell-cell junction organization	1

GO top-level categories

43 GO namespaces:

Category	Terms
cellular anatomical structure	4
cell-cell junction	3
cellular process	2
cell communication	2
signaling	2
cell-cell adhesion	2
regulation of cellular process	1
cellular response to stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of cell-cell adhesion	1
positive regulation of cell adhesion	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
intracellular protein localization	1
regulation of localization	1
protein-containing complex assembly	1
establishment of protein localization to membrane	1
apical junction assembly	1
tight junction assembly	1
establishment of endothelial barrier	1
positive regulation of cell-cell adhesion	1
cell-cell adhesion mediated by cadherin	1
regulation of cell-cell adhesion mediated by cadherin	1
cellular developmental process	1
cellular component organization	1
adherens junction organization	1
cell-cell junction maintenance	1
GTPase binding	1
cell adhesion molecule binding	1
protein binding	1
actin binding	1
protein-containing complex binding	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
anchoring junction	1
membrane protein complex	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 31 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
bicellular tight junction assembly	BP	mutant phenotype
establishment of endothelial intestinal barrier	BP	mutant phenotype
negative regulation of cell migration	BP	mutant phenotype
pore complex assembly	BP	mutant phenotype
positive regulation of cell-cell adhesion	BP	mutant phenotype
positive regulation of cell-cell adhesion mediated by cadherin	BP	mutant phenotype
positive regulation of gene expression	BP	mutant phenotype
cell junction	CC	direct assay
cell-cell contact zone	CC	direct assay
cell-cell junction	CC	direct assay
nucleoplasm	CC	direct assay
plasma membrane	CC	direct assay
pore complex	CC	mutant phenotype
tight junction	CC	direct assay
actin filament binding	MF	direct assay
cadherin binding	MF	high-throughput assay
small GTPase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,884 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AFDN	NECTIN1	Q15223	915
AFDN	NECTIN3	Q9NQS3	868
AFDN	MLLT1	Q03111	867
AFDN	MLLT3	P42568	850
AFDN	AFF1	P51825	848
AFDN	MLLT10	P55197	823
AFDN	NECTIN4	Q96NY8	794
AFDN	RALGDS	Q12967	765
AFDN	MLLT6	P55198	745
AFDN	KMT2A	Q03164	726
AFDN	PVR	P15151	720
AFDN	TJP1	Q07157	719
AFDN	ELL	P55199	708
AFDN	CDH17	Q12864	707
AFDN	NECTIN2	Q92692	698

IntAct

Human interaction partners of AFDN in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 79 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAG	physical association	0.830	2
YWHAH	association	0.740	1
YWHAB	physical association	0.690	1
SRC	direct interaction	0.650	7
NECTIN3	physical association	0.650	4
E	physical association	0.590	4
NECTIN2	direct interaction	0.590	4
DBN1	colocalization	0.540	6
LMO2	direct interaction	0.540	2
YWHAZ	physical association	0.540	1
ABLIM2	association	0.530	2
MRAS	physical association	0.510	2
CDH5	physical association	0.470	1
E6	direct interaction	0.440	3
NECTIN1	direct interaction	0.440	2
ABCC4	direct interaction	0.440	1
ARHGEF16	direct interaction	0.440	1
ASIC3	direct interaction	0.440	1
ATP2B4	direct interaction	0.440	1
CYSLTR2	direct interaction	0.440	1
DGKK	direct interaction	0.440	1
DGKZ	direct interaction	0.440	1
DOCK4	direct interaction	0.440	1
FRMPD4	direct interaction	0.440	1
FZD7	direct interaction	0.440	1
KCNA5	direct interaction	0.440	1
KIR3DL3	direct interaction	0.440	1
MAP2K2	direct interaction	0.440	1
PBK	direct interaction	0.440	1
RALBP1	direct interaction	0.440	1

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
AFDN	“up-regulates activity”	RIT1	binding
AFDN	“up-regulates activity”	RIN1	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Afadin-beta-catenin complex	2	AFDN, CTNNB1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
RAF activation	5	29.0×	4e-05
Adherens junctions interactions	6	25.7×	1e-05
Cell-cell junction organization	5	21.4×	1e-04
EPH-ephrin mediated repulsion of cells	5	18.9×	2e-04
Cell junction organization	5	16.1×	3e-04
EPH-Ephrin signaling	5	14.3×	5e-04
Cell-Cell communication	5	11.9×	8e-04
MITF-M-regulated melanocyte development	5	9.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	27.5×	5e-05
homophilic cell-cell adhesion	6	11.2×	3e-03
regulation of small GTPase mediated signal transduction	5	9.6×	8e-03
intracellular protein localization	6	8.4×	5e-03
cell-cell adhesion	6	8.1×	6e-03
axon guidance	6	7.2×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — BRCA, COADREAD.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for AFDN: 119 ClinVar records (31 pathogenic / likely pathogenic); 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	2
Uncertain significance	23
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 31 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
58456	GRCh38/hg38 6q25.3-27(chr6:159825913-170612001)x1	Pathogenic	criteria provided, single submitter	1
58458	GRCh38/hg38 6q25.3-27(chr6:160359686-170608818)x1	Pathogenic	criteria provided, single submitter	1
58469	GRCh38/hg38 6q26-27(chr6:162789915-170602152)x1	Pathogenic	criteria provided, single submitter	1
58470	GRCh38/hg38 6q26-27(chr6:163420224-170608818)x1	Pathogenic	criteria provided, single submitter	1
58472	GRCh38/hg38 6q27(chr6:166370159-170602152)x1	Pathogenic	criteria provided, single submitter	1
58474	GRCh38/hg38 6q27(chr6:167924952-170602152)x1	Pathogenic	criteria provided, single submitter	1
625656	GRCh37/hg19 6q27(chr6:166517762-170919470)	Pathogenic	criteria provided, single submitter	1
625666	GRCh37/hg19 6q27(chr6:168311806-170881789)	Pathogenic	criteria provided, single submitter	1
1527319	GRCh37/hg19 6q26-27(chr6:161047873-170919482)x1	Pathogenic	criteria provided, single submitter	1
1527320	GRCh37/hg19 6q26-27(chr6:162212864-170919482)x3	Pathogenic	criteria provided, single submitter	1
1527321	GRCh37/hg19 6q26-27(chr6:162381975-170919482)x1	Pathogenic	criteria provided, single submitter	1
1527323	GRCh37/hg19 6q26-27(chr6:163290087-170919482)x1	Pathogenic	criteria provided, single submitter	1
1527327	GRCh37/hg19 6q27(chr6:167317903-170919482)x1	Pathogenic	criteria provided, single submitter	1
3062910	GRCh37/hg19 6q26-27(chr6:162079329-170919482)x1	Pathogenic	criteria provided, single submitter	1
4851055	GRCh37/hg19 6q26-27(chr6:164149175-170919482)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore AFDN’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 3,402):

Position(s)	Effect	Δscore	Sites
6:167864549–167864550	acceptor_loss	1.0000	5
6:167870368	acceptor_gain	1.0000
6:167870373	acceptor_gain	1.0000
6:167870378	acceptor_gain	1.0000
6:167870499–167870500	donor_loss	1.0000	5
6:167875332	acceptor_gain	1.0000
6:167875333–167875334	acceptor_loss	1.0000	3
6:167875496–167875497	donor_loss	1.0000	5
6:167880518–167880519	donor_loss	1.0000	5
6:167889213–167889214	acceptor_loss	1.0000	2

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.65e-05
Breast Invasive Carcinoma (TCGA)	unfavorable	4.57e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	unfavorable	0.000136
Ovary Serous Cystadenocarcinoma (TCGA)	unfavorable	0.000179

Disease associations

OMIM: gene MIM:159559 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
cleft lip/palate	Limited	Autosomal dominant

Mondo (1): cleft lip/palate (MONDO:0016044)

GWAS associations

7 associations:

Study	Trait	p-value
GCST90002387_208	Immature fraction of reticulocytes	2e-13
GCST90002403_618	Red blood cell count	4e-12
GCST90002404_51	Red cell distribution width	2e-10
GCST90002396_503	Mean reticulocyte volume	7e-9
GCST005990_23	Non-albumin protein levels	8e-9
GCST008447_1	Number of alcoholic drinks required to feel an effect (long-term average)	2e-7
GCST001820_2	Metabolite levels (5-HIAA)	6e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0005132	5-HIAA measurement
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, increases expression	4
bisphenol A	increases expression, decreases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Particulate Matter	affects expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
rofecoxib	affects expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
asparanin A	decreases expression	1

Cellosaurus cell lines

14 cell lines: 14 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1418	ML-2	Cancer cell line	Male
CVCL_1619	OCI-AML-2	Cancer cell line	Male
CVCL_2191	SHI-1	Cancer cell line	Male
CVCL_8391	OU-AML-1	Cancer cell line	Male
CVCL_8392	OU-AML-2	Cancer cell line	Male
CVCL_8393	OU-AML-3	Cancer cell line	Male
CVCL_8394	OU-AML-4	Cancer cell line	Male
CVCL_8395	OU-AML-5	Cancer cell line	Male
CVCL_8396	OU-AML-6	Cancer cell line	Male
CVCL_8397	OU-AML-7	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 158 trials:

NCT	Phase	Status	Title
NCT04234971	Phase 4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	Phase 4	RECRUITING	Ketorolac in Palatoplasty
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT03766217	Phase 3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	Phase 3	UNKNOWN	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00930124	Phase 2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT06408337	Phase 1/2	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
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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
NCT03877666	Not specified	COMPLETED	Assessment of the Influence of Cleft Repair on Microcirculation of the Palate
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NCT04108416	Not specified	COMPLETED	Unilateral Cleft Repair in One Surgery With Pure Primary Healing
NCT04236466	Not specified	UNKNOWN	Transverse Dento-skeletal Effects of Two Rapid Palatal Expansion Appliances in Cleft Lip and Palate Patients
NCT04331379	Not specified	COMPLETED	Effectiveness of Nasal-alar Elevator Combined With Taping Vs. Taping Alone on Improving the Nose Esthetics and Maxillary Arch Dimensions in Infants With Unilateral Complete Cleft Lip and Palate
NCT04331977	Not specified	COMPLETED	Effectiveness of Two Maxillary Expanders in Improving the Transverse Skeletal and Dental Dimensions in Patients With Cleft Lip and Palate
NCT04354116	Not specified	UNKNOWN	MARPE in Patients With Cleft Lip and Palate
NCT04369638	Not specified	TERMINATED	Fabrication of Naso-alveolar Molding (NAM) Appliance in Cleft Lip and Palate (CLP) From Digital Magnetic Resonance Imaging (MRI) Face Scan
NCT04381078	Not specified	UNKNOWN	Methods of Providing Information Prior to an Alveolar Bone Graft
NCT04384276	Not specified	COMPLETED	Weigh Easy: Simplifying Home Weight Monitoring for Infants
NCT04422847	Not specified	RECRUITING	Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect
NCT04422964	Not specified	UNKNOWN	Use of Computer Aided Design and 3D Printing for Anesthesiology Management in a Pediatric Patient With Cleft Facial Defect (3D Obturator) - Pilot Trial
NCT04455035	Not specified	TERMINATED	DynaCleft® Effects on Soft Tissues and on Quality of Life for Incomplete Unilateral Cleft Lip Infants