CKAP2L

Summary

CKAP2L (cytoskeleton associated protein 2L, HGNC:26877) is a protein-coding gene on chromosome 2q14.1, encoding Cytoskeleton-associated protein 2-like (Q8IYA6). Microtubule-associated protein required for mitotic spindle formation and cell-cycle progression in neural progenitor cells.

The protein encoded by this gene is thought to be a mitotic spindle protein important to neural stem or progenitor cells. Mutations in this gene have been associated with spindle organization defects, including mitotic spindle defects, lagging chromosomes, and chromatin bridges. There is evidence that mutations in this gene are associated with Filippi syndrome, characterized by growth defects, microcephaly, intellectual disability, facial feature defects, and syndactyly. There is a pseudogene of this gene on chromosome 20. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 150468 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Filippi syndrome (Definitive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 266 total — 14 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 60
• MANE Select transcript: NM_152515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26877
Approved symbol	CKAP2L
Name	cytoskeleton associated protein 2L
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40629, radmis
Ensembl gene	ENSG00000169607
Ensembl biotype	protein_coding
OMIM	616174
Entrez	150468

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000302450, ENST00000435431, ENST00000461876, ENST00000474331, ENST00000481732, ENST00000497357, ENST00000937152, ENST00000937153

RefSeq mRNA: 2 — MANE Select: NM_152515 NM_001304361, NM_152515

CCDS: CCDS2100

Canonical transcript exons

ENST00000302450 — 9 exons

Exon	Start	End
ENSE00001301356	112736349	112739048
ENSE00001844631	112764562	112764609
ENSE00003520519	112760713	112760764
ENSE00003538103	112762503	112762569
ENSE00003546195	112755977	112757214
ENSE00003601555	112740818	112741007
ENSE00003621582	112742706	112742769
ENSE00003656660	112752267	112752474
ENSE00003690819	112746420	112746575

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 95.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4139 / max 173.3405, expressed in 1266 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30155	9.2500	1257
202349	0.1638	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.55	gold quality
ganglionic eminence	UBERON:0004023	90.59	gold quality
embryo	UBERON:0000922	90.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.36	gold quality
oocyte	CL:0000023	86.08	gold quality
secondary oocyte	CL:0000655	84.13	gold quality
bone marrow cell	CL:0002092	81.55	gold quality
bone marrow	UBERON:0002371	81.17	gold quality
trabecular bone tissue	UBERON:0002483	76.55	gold quality
stromal cell of endometrium	CL:0002255	76.29	gold quality
adrenal tissue	UBERON:0018303	72.82	gold quality
vermiform appendix	UBERON:0001154	72.39	gold quality
gingival epithelium	UBERON:0001949	72.16	gold quality
rectum	UBERON:0001052	72.07	gold quality
sperm	CL:0000019	71.52	gold quality
cartilage tissue	UBERON:0002418	71.46	gold quality
ileal mucosa	UBERON:0000331	71.39	silver quality
testis	UBERON:0000473	70.79	gold quality
esophagus mucosa	UBERON:0002469	70.05	gold quality
lymph node	UBERON:0000029	69.95	gold quality
esophagus squamous epithelium	UBERON:0006920	69.44	silver quality
lower esophagus mucosa	UBERON:0035834	69.06	gold quality
caecum	UBERON:0001153	69.01	gold quality
right testis	UBERON:0004534	68.88	gold quality
gingiva	UBERON:0001828	68.47	gold quality
left testis	UBERON:0004533	68.36	gold quality
upper arm skin	UBERON:0004263	67.63	gold quality
smooth muscle tissue	UBERON:0001135	67.50	gold quality
epithelium of nasopharynx	UBERON:0001951	67.03	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	475.10
E-MTAB-7052	yes	230.20
E-MTAB-7249	yes	140.30
E-MTAB-6678	yes	8.60
E-ANND-3	yes	5.40
E-CURD-11	no	498.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting CKAP2L, 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-4425	100.00	67.59	1049
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-7849-3P	99.47	68.17	1224

Literature-anchored findings (GeneRIF, showing 12)

• Radmis, the mouse ortholog of human CKAP2L, is important to mitotic spindle formation and cell-cycle progression of neural stem/neural progenitor cells in mouse. It is abundantly expressed in stem cells, but is down-regulated during differentiation. (PMID:24260314)
• Loss-of-function mutations in CKAP2L are a major cause of Filippi syndrome. (PMID:25439729)
• Development and validation of hub genes for lymph node metastasis in patients with prostate cancer. (PMID:32130760)
• CKAP2L Knockdown Exerts Antitumor Effects by Increasing miR-4496 in Glioblastoma Cell Lines. (PMID:33375517)
• CKAP2L Promotes Non-Small Cell Lung Cancer Progression through Regulation of Transcription Elongation. (PMID:33472893)
• Identification of a novel pathogenic variant in CKAP2L and literature review in a child with Filippi syndrome and congenital talipes equinovarus. (PMID:33913579)
• CKAP2L, as an Independent Risk Factor, Closely Related to the Prognosis of Glioma. (PMID:34631884)
• Novel variants identified in CKAP2L in two siblings with Filippi syndrome. (PMID:34921061)
• CKAP2L, transcriptionally inhibited by FOXP3, promotes breast carcinogenesis through the AKT/mTOR pathway. (PMID:35065924)
• CKAP2L, a crucial target of miR-326, promotes prostate cancer progression. (PMID:35715760)
• Pan-cancer analysis reveals the prognostic and immunotherapeutic value of cytoskeleton-associated protein 2-like. (PMID:37225919)
• IGF2BP2 promotes ovarian cancer growth and metastasis by upregulating CKAP2L protein expression in an m[6] A-dependent manner. (PMID:37665628)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ckap2l	ENSDARG00000100573
mus_musculus	Ckap2l	ENSMUSG00000048327
rattus_norvegicus	Ckap2l	ENSRNOG00000026143

Paralogs (1): CKAP2 (ENSG00000136108)

Protein

Protein identifiers

Cytoskeleton-associated protein 2-like — Q8IYA6 (reviewed: Q8IYA6)

Alternative names: Radial fiber and mitotic spindle protein

All UniProt accessions (2): F8WBE0, Q8IYA6

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-associated protein required for mitotic spindle formation and cell-cycle progression in neural progenitor cells.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle pole.

Post-translational modifications. Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C).

Disease relevance. Filippi syndrome (FLPIS) [MIM:272440] A rare disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The KEN box is required for the association with the APC/C-Cdh1 complex, ubiquitination and degradation.

Induction. Expression is cell-cycle dependent. Undetectable in interphase and prophase, strong expression at the spindle pole throughout metaphase to telophase.

Similarity. Belongs to the CKAP2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IYA6-1	1	yes
Q8IYA6-2	2
Q8IYA6-3	3

RefSeq proteins (2): NP_001291290, NP_689728* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029197	CKAP2_C	Domain
IPR052855	CKAP2-like	Family

Pfam: PF15297

UniProt features (33 total): sequence variant 10, compositionally biased region 5, region of interest 4, modified residue 3, splice variant 3, sequence conflict 3, cross-link 2, chain 1, mutagenesis site 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYA6-F1	54.68	0.08

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 (5): 204, 742, 745, 198, 198

Mutagenesis-validated functional residues (1):

Position	Phenotype
198	abrogates sumoylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 288 (showing top): HORIUCHI_WTAP_TARGETS_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_MICROTUBULE_ORGANIZING_CENTER, CEBALLOS_TARGETS_OF_TP53_AND_MYC_DN, FISCHER_G2_M_CELL_CYCLE, GOCC_CENTROSOME, KUNINGER_IGF1_VS_PDGFB_TARGETS_DN, FISCHER_DREAM_TARGETS, chr2q14, GOCC_SPINDLE, NUYTTEN_EZH2_TARGETS_DN, GOCC_MITOTIC_SPINDLE, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GEORGES_TARGETS_OF_MIR192_AND_MIR215, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (8): spindle pole (GO:0000922), centrosome (GO:0005813), cytosol (GO:0005829), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), mitotic spindle (GO:0072686), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
spindle	2
centriole	1
microtubule organizing center	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CKAP2L	MELK	Q14680	643
CKAP2L	DLGAP5	Q15398	632
CKAP2L	BUB1	O43683	627
CKAP2L	HJURP	Q8NCD3	620
CKAP2L	ASPM	Q8IZT6	595
CKAP2L	CEP55	Q53EZ4	535
CKAP2L	CCNB2	O95067	519
CKAP2L	CDC45	O75419	514
CKAP2L	AURKB	Q96GD4	498
CKAP2L	TK1	P04183	477
CKAP2L	KIF18B	Q86Y91	474
CKAP2L	CKS2	P33552	454
CKAP2L	STPG3	Q8N7X2	447
CKAP2L	NCAPG	Q9BPX3	431
CKAP2L	TTK	P33981	419

IntAct

25 interactions, top by confidence:

A	B	Type	Score
N	RBM47	psi-mi:“MI:0914”(association)	0.530
PDGFRL	ANKRD28	psi-mi:“MI:0914”(association)	0.530
RBMX2	WDR46	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
CKAP2L	SIRT5	psi-mi:“MI:0915”(physical association)	0.400
ARL9	CKAP2L	psi-mi:“MI:0915”(physical association)	0.400
N	RBM47	psi-mi:“MI:0914”(association)	0.350
MAP4	TUBA1B	psi-mi:“MI:0914”(association)	0.350
STX6	SNAP23	psi-mi:“MI:0914”(association)	0.350
LIN28A	GTPBP10	psi-mi:“MI:0914”(association)	0.350
LYAR	PES1	psi-mi:“MI:0914”(association)	0.350
RPL3	GTPBP10	psi-mi:“MI:0914”(association)	0.350
RRS1	ZNF316	psi-mi:“MI:0914”(association)	0.350
SURF6	U2SURP	psi-mi:“MI:0914”(association)	0.350
	TTC8	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
DCTN1	KIF2A	psi-mi:“MI:2364”(proximity)	0.270
DCTN1	NACA	psi-mi:“MI:2364”(proximity)	0.270
PCM1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
SPICE1	CCDC66	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (32): CKAP2L (Affinity Capture-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Synthetic Lethality), CKAP2L (Negative Genetic), CKAP2L (Affinity Capture-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Proximity Label-MS), CKAP2L (Affinity Capture-MS)

ESM2 similar proteins: A0JMT0, A0JMZ1, A1L2F3, A1L3I5, A5D7U0, A8PUI7, A9C3N6, O13024, O14216, O60293, O75167, P53352, P86345, P86346, P86347, Q0IHP2, Q0P5H2, Q0V9F7, Q15398, Q1W1G1, Q24595, Q2YDJ0, Q32N93, Q3KPK4, Q3KQW7, Q4KLP8, Q4V7H8, Q53HL2, Q563C3, Q5BKG8, Q5RBS5, Q5XG21, Q5XLR4, Q5ZJU5, Q6CK38, Q6CNI5, Q6FME9, Q6GLC7, Q76FK4, Q7K3L1

Diamond homologs: A5PK21, Q3V1H1, Q7TS74, Q8IYA6, A5D7U0, Q5R7F8, Q8WWK9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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.

GO biological processes:

GO term	Partners	Fold	FDR
cell division	6	9.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	5
Uncertain significance	144
Likely benign	51
Benign	34

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1040806	NM_152515.5(CKAP2L):c.2066G>A (p.Arg689His)	Pathogenic
1183968	NM_152515.5(CKAP2L):c.1463_1467del (p.Thr488fs)	Pathogenic
1292042	NM_152515.5(CKAP2L):c.1169_1173del (p.Ile390fs)	Pathogenic
162384	NM_152515.5(CKAP2L):c.571dup (p.Ile191fs)	Pathogenic
162385	NM_152515.5(CKAP2L):c.2T>C (p.Met1Thr)	Pathogenic
162386	NM_152515.5(CKAP2L):c.78_79insTT (p.Gly27fs)	Pathogenic
162387	NM_152515.5(CKAP2L):c.751del (p.Ser251fs)	Pathogenic
162388	NM_001304361.2(CKAP2L):c.-280-59_-11del	Pathogenic
162389	NM_152515.5(CKAP2L):c.554_555del (p.Lys185fs)	Pathogenic
2572498	NM_152515.5(CKAP2L):c.1004_1029dup (p.Tyr344fs)	Pathogenic
2691463	NM_152515.5(CKAP2L):c.1046_1053dup (p.Lys352fs)	Pathogenic
3767278	NM_152515.5(CKAP2L):c.46C>T (p.Gln16Ter)	Pathogenic
4749713	NM_152515.5(CKAP2L):c.1573_1574del (p.Leu525fs)	Pathogenic
984719	NM_152515.5(CKAP2L):c.1822+1G>A	Pathogenic
3337767	NM_152515.5(CKAP2L):c.2_3insA (p.Met1fs)	Likely pathogenic
3337768	NM_152515.5(CKAP2L):c.953_954del (p.Ile318fs)	Likely pathogenic
3351265	NM_152515.5(CKAP2L):c.40G>T (p.Glu14Ter)	Likely pathogenic
804387	NM_152515.5(CKAP2L):c.552_555del (p.Asn184fs)	Likely pathogenic
817428	NM_152515.5(CKAP2L):c.1634dup (p.Leu545fs)	Likely pathogenic

SpliceAI

1496 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112739047:TT:T	acceptor_gain	1.0000
2:112739049:C:CC	acceptor_gain	1.0000
2:112742705:CCTT:C	donor_gain	1.0000
2:112742766:TTGG:T	acceptor_gain	1.0000
2:112742767:TGG:T	acceptor_gain	1.0000
2:112742768:GG:G	acceptor_gain	1.0000
2:112742770:C:CC	acceptor_gain	1.0000
2:112742770:CT:C	acceptor_loss	1.0000
2:112742771:T:A	acceptor_loss	1.0000
2:112746413:TAC:T	donor_loss	1.0000
2:112746416:T:TG	donor_loss	1.0000
2:112746417:CACTG:C	donor_loss	1.0000
2:112746418:A:AC	donor_gain	1.0000
2:112746418:A:T	donor_loss	1.0000
2:112746419:C:CA	donor_gain	1.0000
2:112746419:CT:C	donor_gain	1.0000
2:112752261:ACTT:A	donor_loss	1.0000
2:112752262:CTTA:C	donor_loss	1.0000
2:112752263:TTA:T	donor_loss	1.0000
2:112752264:T:TC	donor_loss	1.0000
2:112752265:A:AC	donor_gain	1.0000
2:112752265:AC:A	donor_gain	1.0000
2:112752265:ACC:A	donor_gain	1.0000
2:112752266:C:CC	donor_gain	1.0000
2:112752266:CC:C	donor_gain	1.0000
2:112752266:CCC:C	donor_gain	1.0000
2:112752473:TC:T	acceptor_gain	1.0000
2:112752474:CC:C	acceptor_gain	1.0000
2:112752474:CCTGA:C	acceptor_loss	1.0000
2:112757211:TAGT:T	acceptor_gain	1.0000

AlphaMissense

4892 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112752458:A:G	W471R	0.994
2:112752458:A:T	W471R	0.994
2:112752456:C:A	W471C	0.993
2:112752456:C:G	W471C	0.993
2:112746440:C:G	A580P	0.989
2:112738996:G:T	R689S	0.988
2:112746494:C:G	A562P	0.987
2:112746506:A:G	W558R	0.985
2:112746506:A:T	W558R	0.985
2:112738985:C:A	R692S	0.984
2:112738985:C:G	R692S	0.984
2:112752457:C:G	W471S	0.981
2:112738868:A:C	N731K	0.980
2:112738868:A:T	N731K	0.980
2:112738995:C:G	R689P	0.980
2:112746507:G:C	F557L	0.980
2:112746507:G:T	F557L	0.980
2:112746509:A:G	F557L	0.980
2:112738998:C:G	R688P	0.979
2:112752295:A:G	L525P	0.979
2:112752466:A:G	L468P	0.979
2:112739001:A:T	V687E	0.977
2:112752449:A:G	S474P	0.977
2:112762543:A:G	Y22H	0.977
2:112738860:A:G	L734P	0.976
2:112762551:A:G	L19P	0.976
2:112742756:A:G	L591S	0.975
2:112752287:A:G	C528R	0.974
2:112752429:T:A	K480N	0.974
2:112752429:T:G	K480N	0.974

dbSNP variants (sampled 300 via entrez): RS1000031692 (2:112765967 C>T), RS1000058680 (2:112762194 G>A), RS1000270709 (2:112766064 C>G), RS1000271231 (2:112761048 A>G), RS1000377970 (2:112759984 C>T), RS1000390570 (2:112742568 T>C), RS1000808924 (2:112766281 C>A,T), RS1000829518 (2:112736313 T>C), RS1000856526 (2:112762402 T>C), RS1000933725 (2:112755533 G>C), RS1001009126 (2:112747665 C>T), RS1001029235 (2:112748759 G>T), RS1001138480 (2:112754477 A>G), RS1001299911 (2:112756593 G>T), RS1001369818 (2:112747875 A>G)

Disease associations

OMIM: gene MIM:616174 | disease phenotypes: MIM:272440

GenCC curated gene-disease

Disease	Classification	Inheritance
Filippi syndrome	Definitive	Autosomal recessive

Mondo (3): Filippi syndrome (MONDO:0010092), intellectual disability (MONDO:0001071), hypogonadism (MONDO:0002146)

Orphanet (2): Filippi syndrome (Orphanet:3255), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000062	Ambiguous genitalia
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000494	Downslanted palpebral fissures
HP:0000505	Visual impairment
HP:0000520	Proptosis
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000691	Microdontia
HP:0000954	Single transverse palmar crease
HP:0000998	Hypertrichosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001328	Specific learning disability
HP:0001332	Dystonia
HP:0001376	Limitation of joint mobility
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004599_280	Mean platelet volume	5.000000e-24
GCST006656_2	Dysmenorrheic pain severity	2.000000e-16
GCST008751_1	Gestational age at birth (child effect)	4.000000e-14
GCST008752_1	Post-term birth	4.000000e-08
GCST010396_40	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST90002395_338	Mean platelet volume	3.000000e-54
GCST90002395_339	Mean platelet volume	6.000000e-18

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007889	dysmenorrheic pain measurement
EFO:0005112	gestational age
EFO:0006921	birth measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007006	Hypogonadism	C19.391.482
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C538152	Filippi syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, decreases expression	3
Cyclosporine	decreases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
palbociclib	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol Z	increases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00194675	PHASE4	COMPLETED	TRADE-Testosterone Replacement and Dutasteride Effectiveness
NCT00240981	PHASE4	TERMINATED	TOM: Testosterone in Older Men With Sarcopenia
NCT00287586	PHASE4	COMPLETED	Testosterone Replacement in Older Men and Atherosclerosis Progression
NCT00304213	PHASE4	WITHDRAWN	Does Testosterone Improve Function in Hypogonadal Older Men
NCT00349362	PHASE4	COMPLETED	Testosterone for Men With Insulin Treated Type 2 Diabetes
NCT00421460	PHASE4	COMPLETED	The Therapy of Nebido as Mono or in Combination With PDE-5 Inhibitors in Hypogonadal Patients With Erectile Dysfunction
NCT00440440	PHASE4	WITHDRAWN	Effect of Testosterone Gel Replacement on Fat Mass in Males With Low Testosterone Levels and Diabetes
NCT00487734	PHASE4	COMPLETED	Effect of Testosterone Replacement on Insulin Resistance
NCT00504712	PHASE4	COMPLETED	Testosterone for Peripheral Vascular Disease
NCT00700024	PHASE4	UNKNOWN	Odense Androgen Study - The Effect of Testim and Training in Hypogonadal Men
NCT00710827	PHASE4	WITHDRAWN	Nebido Versus Placebo in Elderly Men With Typical Symptoms of Late Onset Hypogonadism Over a Period of 54 Weeks
NCT00752869	PHASE4	COMPLETED	Efficacy Study for Use of Dutasteride (Avodart) With Testosterone Replacement
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01084369	PHASE4	TERMINATED	Effect of Testosterone on Endothelial Function and Microcirculation in Type 2 Diabetic Patients With Hypogonadism
NCT01092858	PHASE4	TERMINATED	NEBIDO in Symptomatic Late Onset Hypogonadism (SLOH)
NCT01107067	PHASE4	COMPLETED	Testosterone Replacement Therapy Decreases Plasma Paraoxonase 1 Enzyme Activity In Male Patients With Hypogonadism
NCT01123278	PHASE4	COMPLETED	Testosterone Replacement in Metabolic Syndrome and Inflammation
NCT01127659	PHASE4	COMPLETED	Testosterone Replacement in Men With Diabetes and Obesity
NCT01160341	PHASE4	COMPLETED	Metabolic Syndrome Criteria and the Effect of Testosterone Treatment in Young Men With Hypogonadism
NCT01560546	PHASE4	COMPLETED	Testosterone Therapy of Men With Type 2 Diabetes Mellitus (T2DM)
NCT01689896	PHASE4	WITHDRAWN	Testosterone and Pain Sensitivity
NCT01748370	PHASE4	COMPLETED	Vitamin D Treatment and Hypogonadism in Men
NCT01893281	PHASE4	COMPLETED	The Effect of Testosterone Topical Solution (LY900011) in Hypogonadal Men With Suboptimal Response to a Topical Testosterone Gel
NCT02102646	PHASE4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02111434	PHASE4	COMPLETED	Visceral Adiposity Index and Triglyceride/High-density Lipoprotein Cholesterol Ratio in the Congenital Hypogonadotropic Hypogonadism and Effect of Testosteron Treatment
NCT02111473	PHASE4	COMPLETED	The Effect of Testosteron Replacement Treatment on the Fibroblast Growth Factor-23, Asymmetric Dimethylarginine and Vitamin D Levels in the Congenital Hypogonadotropic Hypogonadism
NCT02366975	PHASE4	COMPLETED	TRT on BPH Hypoganadal MetS Patients. Florence-PROTEST
NCT02433730	PHASE4	COMPLETED	Testosterone Therapy in Hypogonadal Men Treated With Opioids
NCT02937740	PHASE4	COMPLETED	Open-Label Study, Evaluating Patient Satisfaction and Symptom Improvement When Treating Male Hypogonadism With Natesto™
NCT02959853	PHASE4	COMPLETED	Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)
NCT03057899	PHASE4	COMPLETED	Efficacy of Fenugreek Seed and Lespedeza Cuneata in TDS
NCT03126656	PHASE4	COMPLETED	Effects of Testosterone on Myocardial Repolarization
NCT03518034	PHASE4	COMPLETED	A Study to Evaluate the Effect of Testosterone Replacement Therapy (TRT) on the Incidence of Major Adverse Cardiovascular Events (MACE) and Efficacy Measures in Hypogonadal Men
NCT03619330	PHASE4	COMPLETED	Testosterone Replacement Therapy and Liraglutide Effects on Weight Loss in Hypogonadism.
NCT03887936	PHASE4	COMPLETED	Testosterone Therapy and Bone Quality in Men With Diabetes and Hypogonadism
NCT04274894	PHASE4	COMPLETED	A Study of the Effect of Topical Testosterone Replacement Therapy on Blood Pressure in Adult Male Participants With Hypogonadism