CLIP2

Summary

CLIP2 (CAP-Gly domain containing linker protein 2, HGNC:2586) is a protein-coding gene on chromosome 7q11.23, encoding CAP-Gly domain-containing linker protein 2 (Q9UDT6). Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions.

The protein encoded by this gene belongs to the family of cytoplasmic linker proteins, which have been proposed to mediate the interaction between specific membranous organelles and microtubules. This protein was found to associate with both microtubules and an organelle called the dendritic lamellar body. This gene is hemizygously deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternative splicing of this gene generates 2 transcript variants.

Source: NCBI Gene 7461 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 193 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 186
• MANE Select transcript: NM_003388

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2586
Approved symbol	CLIP2
Name	CAP-Gly domain containing linker protein 2
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	CLIP-115, KIAA0291, WSCR4, CLIP, WSCR3
Ensembl gene	ENSG00000106665
Ensembl biotype	protein_coding
OMIM	603432
Entrez	7461

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 4 retained_intron

ENST00000223398, ENST00000361545, ENST00000474962, ENST00000482424, ENST00000487091, ENST00000487447, ENST00000491075, ENST00000493166, ENST00000884298, ENST00000884299, ENST00000884300, ENST00000884301, ENST00000930626, ENST00000930627, ENST00000930628, ENST00000930629, ENST00000930630, ENST00000941414, ENST00000941415, ENST00000941416, ENST00000941417, ENST00000941418, ENST00000941419, ENST00000941420, ENST00000941421, ENST00000941422, ENST00000941423

RefSeq mRNA: 2 — MANE Select: NM_003388 NM_003388, NM_032421

CCDS: CCDS5569, CCDS5570

Canonical transcript exons

ENST00000223398 — 17 exons

Exon	Start	End
ENSE00000691488	74400370	74400555
ENSE00000691492	74380806	74380863
ENSE00000691493	74375887	74376822
ENSE00001039248	74403837	74405935
ENSE00001039278	74372932	74373036
ENSE00001128453	74317480	74317667
ENSE00001148381	74397074	74397233
ENSE00001148391	74389103	74389259
ENSE00001148405	74364255	74364315
ENSE00001148414	74356410	74356623
ENSE00001148424	74353880	74354004
ENSE00001148434	74338448	74339004
ENSE00001400047	74401505	74401567
ENSE00002467763	74357280	74357477
ENSE00002512403	74360175	74360278
ENSE00003486023	74386521	74386604
ENSE00003896646	74289407	74289734

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.4973 / max 187.9459, expressed in 1721 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79085	13.4973	1721

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.22	gold quality
ganglionic eminence	UBERON:0004023	95.79	gold quality
spinal cord	UBERON:0002240	95.64	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.16	gold quality
prefrontal cortex	UBERON:0000451	95.05	gold quality
inferior olivary complex	UBERON:0002127	94.87	gold quality
cranial nerve II	UBERON:0000941	94.62	gold quality
right frontal lobe	UBERON:0002810	94.51	gold quality
amygdala	UBERON:0001876	94.19	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.89	gold quality
postcentral gyrus	UBERON:0002581	93.87	gold quality
frontal cortex	UBERON:0001870	93.85	gold quality
anterior cingulate cortex	UBERON:0009835	93.83	gold quality
cingulate cortex	UBERON:0003027	93.82	gold quality
neocortex	UBERON:0001950	93.59	gold quality
hypothalamus	UBERON:0001898	93.31	gold quality
parietal lobe	UBERON:0001872	93.21	gold quality
Ammon’s horn	UBERON:0001954	92.99	gold quality
cerebral cortex	UBERON:0000956	92.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.93	gold quality
substantia nigra	UBERON:0002038	92.71	gold quality
sural nerve	UBERON:0015488	92.71	gold quality
ventricular zone	UBERON:0003053	92.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.62	gold quality
telencephalon	UBERON:0001893	92.61	gold quality
temporal lobe	UBERON:0001871	92.57	gold quality
midbrain	UBERON:0001891	92.48	gold quality
putamen	UBERON:0001874	92.35	gold quality
corpus callosum	UBERON:0002336	92.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.29
E-GEOD-111727	no	308.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting CLIP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106

Literature-anchored findings (GeneRIF, showing 8)

• Data show that gene CLIP2 was specifically overexpressed in the exposed cases. (PMID:21606360)
• CLIP2 haploinsufficiency by itself does not lead to the physical or cognitive characteristics of the Williams-Beuren syndrome; GTF2IRD1 and GTF2I are the main genes causing the cognitive defects (PMID:22608712)
• CLIP2 protein expression is elevated in papillary thyroid carcinomas from patients exposed to radioiodine fallout compared with a nonexposed control group. (PMID:25284583)
• A clear radiation dose-response relationship for the CLIP2 marker expression in post-Chernobyl papillary thyroid carcinomas (PMID:25957251)
• Cross checking with epidemiological estimates and model validation suggests that CLIP2 is a marker of high precision. CLIP2 leaves an imprint in the epidemiological incidence data which is typical for a driver gene. (PMID:27729373)
• CILP-2 is a novel secreted protein and demonstrated that circulating CILP-2 levels were elevated in both IGT and nT2DM subjects and associated with IR. CILP-2 overexpression promoted hepatic IR in HFD-fed mice, increased PEPCK expression and suppressed insulin signaling in hepatocytes. (PMID:30896018)
• Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis. (PMID:32734598)
• Clinical, pathologic, and genomic characteristics of two pediatric glioneuronal tumors with a CLIP2::MET fusion. (PMID:38650040)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	clip2	ENSDARG00000059596
mus_musculus	Clip2	ENSMUSG00000063146
rattus_norvegicus	Clip2	ENSRNOG00000021611

Paralogs (4): CLIP3 (ENSG00000105270), CLIP4 (ENSG00000115295), CLIP1 (ENSG00000130779), DCTN1 (ENSG00000204843)

Protein

Protein identifiers

CAP-Gly domain-containing linker protein 2 — Q9UDT6 (reviewed: Q9UDT6)

Alternative names: Cytoplasmic linker protein 115, Cytoplasmic linker protein 2, Williams-Beuren syndrome chromosomal region 3 protein, Williams-Beuren syndrome chromosomal region 4 protein

All UniProt accessions (3): Q9UDT6, H7C4L6, H7C5H8

UniProt curated annotations — full annotation on UniProt →

Function. Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations.

Subunit / interactions. Interacts with CLASP1 and CLASP2. Binds preferentially to tyrosinated microtubules, and only marginally to detyrosinated microtubules.

Subcellular location. Cytoplasm. Cytoskeleton.

Disease relevance. CLIP2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of CLIP2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease. However, it has been demonstrated that haploinsufficiency of this gene alone is not sufficient to cause any of the cognitive or facial features of WBS.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UDT6-1	1	yes
Q9UDT6-2	2

RefSeq proteins (2): NP_003379, NP_115797 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000938	CAP-Gly_domain	Domain
IPR036859	CAP-Gly_dom_sf	Homologous_superfamily

Pfam: PF01302

UniProt features (49 total): strand 14, modified residue 8, compositionally biased region 7, region of interest 5, coiled-coil region 3, helix 3, turn 3, domain 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2CP2	SOLUTION NMR
2CP3	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UDT6-F1	75.25	0.46

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 (8): 49, 202, 207, 211, 314, 923, 973, 979

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 593 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, FREAC2_01, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_493, BLALOCK_ALZHEIMERS_DISEASE_UP, PARK_HSC_VS_MULTIPOTENT_PROGENITORS_UP, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, HFH1_01, TTGGAGA_MIR5155P_MIR519E, FREAC4_01, chr7q11, YAGI_AML_RELAPSE_PROGNOSIS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_UP, SOX5_01

GO Biological Process (1): cytoplasmic microtubule organization (GO:0031122)

GO Molecular Function (2): microtubule binding (GO:0008017), microtubule plus-end binding (GO:0051010)

GO Cellular Component (8): nucleus (GO:0005634), microtubule associated complex (GO:0005875), cell cortex (GO:0005938), microtubule plus-end (GO:0035371), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule cytoskeleton	2
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
tubulin binding	1
microtubule binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
cytoplasm	1
cell periphery	1
microtubule end	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
polymeric cytoskeletal fiber	1
cytoskeleton	1

Protein interactions and networks

STRING

970 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLIP2	CLASRP	Q8N2M8	974
CLIP2	CLASP2	O75122	955
CLIP2	CLASP1	Q7Z460	912
CLIP2	LIMK1	P53667	863
CLIP2	GTF2IRD1	Q9UHL9	857
CLIP2	TBL2	Q9Y4P3	838
CLIP2	EIF4H	Q15056	815
CLIP2	GTF2I	P78347	773
CLIP2	FZD9	O00144	735
CLIP2	FKBP6	O75344	734
CLIP2	RFC2	P32846	731
CLIP2	FKBP10	Q96AY3	718
CLIP2	STX1A	Q16623	703
CLIP2	TRIM50	Q86XT4	673
CLIP2	BAZ1B	Q9UIG0	659

IntAct

44 interactions, top by confidence:

A	B	Type	Score
FTH1	NCOA4	psi-mi:“MI:0914”(association)	0.790
ARMC8	HTRA2	psi-mi:“MI:0914”(association)	0.750
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
MBIP	TADA2A	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
CLIP2	BCAP31	psi-mi:“MI:0915”(physical association)	0.400
KLC4	PUF60	psi-mi:“MI:0914”(association)	0.350
Timeless	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
Sidt2	PRSS1	psi-mi:“MI:0914”(association)	0.350
MAPRE1	CTNNB1	psi-mi:“MI:0914”(association)	0.350
Dnaaf5	XPOT	psi-mi:“MI:0914”(association)	0.350
TUBA1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
KATNA1	AURKA	psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
MED13L	IGKV1-8	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
TUBB4B	TUBA1B	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): Clasp1 (Reconstituted Complex), CLIP2 (Affinity Capture-Western), CLASP1 (Affinity Capture-Western), CLIP2 (Affinity Capture-MS), CLIP2 (Affinity Capture-MS), CLIP2 (Affinity Capture-MS), CLIP2 (Affinity Capture-MS), CLIP2 (Affinity Capture-MS), CLIP2 (Affinity Capture-RNA), CLIP2 (Affinity Capture-MS), CLIP2 (Affinity Capture-RNA), CLIP2 (Proximity Label-MS), CLASP1 (Reconstituted Complex), CLASP2 (Reconstituted Complex), CLIP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A125S9M4, A0A125S9M5, A8B976, A8WUP2, A8WVU9, B3MNR6, B3NL60, B4G831, B4I5P7, B4JAL5, B4KE73, B4PAF2, B4Q9E6, B9F2Y7, C5DJH6, C5DY19, F1M5N7, F4K0J3, G5ECG0, G5EGS3, O55156, O61493, O75037, P11929, P22488, P34562, P45970, P90970, P92199, Q21443, Q23529, Q24185, Q29N92, Q2KN96, Q2KN97, Q2KN98, Q2KN99, Q2KNA1, Q60YN5, Q69YQ0

Diamond homologs: A0A287B8J2, B9EHT4, O08788, O42184, O42667, O55156, P28023, P30622, P33420, P35458, Q10235, Q14203, Q20728, Q54Z01, Q5E951, Q5R686, Q5U243, Q66HD5, Q6PCJ1, Q8CI96, Q8N3C7, Q922J3, Q96DZ5, Q99426, Q9D1E6, Q9JK25, Q9NQT8, Q9UDT6, Q9VJE5, Q9Z0H8, E9Q309, P13496, P34531, Q01397, Q15813, Q32KS0, Q55CN0, Q5FVQ9, Q5RBD9, Q5U378

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CLASP1	“up-regulates activity”	CLIP2	binding
CLASP2	“up-regulates activity”	CLIP2	binding
CLIP2	up-regulates	Microtubule_polimerization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
Kinesins	5	18.6×	6e-04
Golgi-to-ER retrograde transport	5	13.8×	1e-03
Mitotic G2-G2/M phases	5	13.2×	1e-03
G2/M Transition	5	13.2×	1e-03
COPI-dependent Golgi-to-ER retrograde traffic	5	11.6×	1e-03
MHC class II antigen presentation	6	11.2×	7e-04
Intra-Golgi and retrograde Golgi-to-ER traffic	5	10.9×	2e-03
Mitotic Metaphase and Anaphase	5	10.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
microtubule cytoskeleton organization	6	12.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	139
Likely benign	21
Benign	13

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
523284	GRCh37/hg19 7q11.23(chr7:72772522-74133319)	Pathogenic
563406	GRCh37/hg19 7q11.23(chr7:72612042-74574641)x1	Pathogenic
393774	GRCh37/hg19 7q11.23(chr7:73791725-74133273)x1	Likely pathogenic

SpliceAI

3406 predictions. Top by Δscore:

Variant	Effect	Δscore
7:74289732:AAGG:A	donor_loss	1.0000
7:74289736:T:G	donor_loss	1.0000
7:74317471:T:TA	acceptor_gain	1.0000
7:74317476:GCAG:G	acceptor_loss	1.0000
7:74317478:AG:A	acceptor_gain	1.0000
7:74317478:AGGT:A	acceptor_gain	1.0000
7:74317479:G:A	acceptor_loss	1.0000
7:74317479:GG:G	acceptor_gain	1.0000
7:74317479:GGT:G	acceptor_gain	1.0000
7:74317479:GGTG:G	acceptor_gain	1.0000
7:74317479:GGTGA:G	acceptor_gain	1.0000
7:74317663:GGAAG:G	donor_gain	1.0000
7:74317664:GAAG:G	donor_gain	1.0000
7:74317664:GAAGG:G	donor_gain	1.0000
7:74317665:A:T	donor_gain	1.0000
7:74317666:AG:A	donor_gain	1.0000
7:74317666:AGG:A	donor_loss	1.0000
7:74317667:GG:G	donor_gain	1.0000
7:74317668:G:GA	donor_loss	1.0000
7:74317668:G:GG	donor_gain	1.0000
7:74339001:GCTG:G	donor_gain	1.0000
7:74339003:TGGTG:T	donor_loss	1.0000
7:74339005:G:GG	donor_gain	1.0000
7:74339005:GTGA:G	donor_loss	1.0000
7:74339006:TGAG:T	donor_loss	1.0000
7:74339007:GAGT:G	donor_loss	1.0000
7:74353975:G:T	donor_gain	1.0000
7:74354003:AGG:A	donor_loss	1.0000
7:74354004:GGTAT:G	donor_loss	1.0000
7:74354005:G:GC	donor_loss	1.0000

AlphaMissense

6743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:74338633:T:C	F103L	1.000
7:74338634:T:C	F103S	1.000
7:74338634:T:G	F103C	1.000
7:74338635:C:A	F103L	1.000
7:74338635:C:G	F103L	1.000
7:74338648:T:A	W108R	1.000
7:74338648:T:C	W108R	1.000
7:74338650:G:C	W108C	1.000
7:74338650:G:T	W108C	1.000
7:74338655:G:A	G110D	1.000
7:74338691:G:A	G122D	1.000
7:74338741:T:C	F139L	1.000
7:74338742:T:C	F139S	1.000
7:74338743:C:A	F139L	1.000
7:74338743:C:G	F139L	1.000
7:74339000:T:A	V225E	1.000
7:74353881:T:A	V227D	1.000
7:74353892:A:G	K231E	1.000
7:74353894:G:C	K231N	1.000
7:74353894:G:T	K231N	1.000
7:74353898:G:C	G233R	1.000
7:74353899:G:A	G233D	1.000
7:74353899:G:T	G233V	1.000
7:74353916:G:T	G239W	1.000
7:74353928:T:C	F243L	1.000
7:74353928:T:G	F243V	1.000
7:74353929:T:C	F243S	1.000
7:74353929:T:G	F243C	1.000
7:74353930:T:A	F243L	1.000
7:74353930:T:G	F243L	1.000

dbSNP variants (sampled 300 via entrez): RS1000047359 (7:74336110 T>C), RS1000108748 (7:74374889 A>G), RS1000117789 (7:74332687 C>T), RS1000150778 (7:74380526 A>G), RS1000206647 (7:74380109 T>G), RS1000277431 (7:74339152 T>C), RS1000284998 (7:74298110 C>T), RS1000304157 (7:74360982 G>C), RS1000375236 (7:74345395 G>A), RS1000413178 (7:74386637 G>A), RS1000437842 (7:74304982 A>G), RS1000453379 (7:74331155 G>A), RS1000473003 (7:74326560 G>A,T), RS1000491413 (7:74345051 C>T), RS1000540888 (7:74378763 A>C)

Disease associations

OMIM: gene MIM:603432 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): microcephaly (MONDO:0001149)

Orphanet (0):

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008771_2	Age at suicide	1.000000e-07
GCST010584_1	Autism spectrum disorders (social interaction)	3.000000e-08
GCST012256_21	SAPHO syndrome	4.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006882	suicide behaviour measurement
EFO:0005426	autism spectrum disorder symptom

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Cyclosporine	increases expression	3
Cisplatin	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
ethylbenzene	affects cotreatment, decreases expression, increases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
ochratoxin A	increases acetylation	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.