CLTC

Summary

CLTC (clathrin heavy chain, HGNC:2092) is a protein-coding gene on chromosome 17q23.1, encoding Clathrin heavy chain 1 (Q00610). Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. It is a common-essential gene (DepMap: required in 99.2% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles are involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules. The basic subunit of the clathrin coat is composed of three heavy chains and three light chains.

Source: NCBI Gene 1213 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal dominant 56 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 1,292 total — 68 pathogenic, 71 likely-pathogenic (top 2% of genes corpus-wide)
• Regional missense constraint (gnomAD): 4 of 9 regions constrained (≈40% of expected missense variation)
• GTEx eGene: eQTL in 8 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 79
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 99.2% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.10 (highly constrained)
• MANE Select transcript: NM_004859
• Interaction hub: 3,626 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2092
Approved symbol	CLTC
Name	clathrin heavy chain
Location	17q23.1
Locus type	gene with protein product
Status	Approved
Aliases	Hc
Ensembl gene	ENSG00000141367
Ensembl biotype	protein_coding
OMIM	118955
Entrez	1213

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 34 protein_coding, 5 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000269122

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

ENST00000269122, ENST00000393043, ENST00000466513, ENST00000472129, ENST00000472651, ENST00000475458, ENST00000483176, ENST00000496076, ENST00000498711, ENST00000579456, ENST00000579815, ENST00000580081, ENST00000584313, ENST00000585198, ENST00000700707, ENST00000700708, ENST00000700709, ENST00000700710, ENST00000700711, ENST00000700712, ENST00000700713, ENST00000700714, ENST00000700715, ENST00000714180, ENST00000714181, ENST00000714182, ENST00000714241, ENST00000714242, ENST00000714243, ENST00000891780, ENST00000891781, ENST00000891782, ENST00000935242, ENST00000935243, ENST00000935244, ENST00000979679, ENST00001040553, ENST00001107014, ENST00001114469, ENST00001114470, ENST00001114471, ENST00001114472, ENST00001127540, ENST00001128848, ENST00001134448

RefSeq mRNA: 2 — MANE Select: NM_004859 NM_001288653, NM_004859

CCDS: CCDS32696, CCDS74115

Canonical transcript exons

ENST00000269122 — 32 exons

Exon	Start	End
ENSE00000948100	59647398	59647666
ENSE00000948103	59655854	59656027
ENSE00000948106	59663842	59663994
ENSE00000948107	59664787	59664909
ENSE00000948110	59666797	59666977
ENSE00000948114	59676954	59677188
ENSE00000948117	59681295	59681478
ENSE00000948118	59681647	59681839
ENSE00000948119	59682271	59682428
ENSE00000948120	59682629	59682793
ENSE00000948121	59682907	59683014
ENSE00000948122	59683095	59683262
ENSE00000948123	59683387	59683536
ENSE00000948124	59683625	59683756
ENSE00000948125	59683875	59683985
ENSE00001159098	59679397	59679519
ENSE00001605197	59680912	59681057
ENSE00001689879	59673647	59673772
ENSE00002214061	59668777	59668940
ENSE00002460256	59644276	59644483
ENSE00002813683	59685587	59685808
ENSE00002922394	59685056	59685226
ENSE00002949725	59690636	59690711
ENSE00003459447	59661443	59661643
ENSE00003574074	59674701	59674843
ENSE00003593471	59666480	59666644
ENSE00003609165	59648240	59648401
ENSE00003611615	59651203	59651316
ENSE00003686268	59666103	59666240
ENSE00003980608	59693728	59696956
ENSE00004021611	59619895	59620173
ENSE00004023301	59660391	59660588

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 241.8927 / max 1315.2092, expressed in 1829 samples.

Highest expression (Bgee): pons, lateral nuclear group of thalamus, Brodmann (1909) area 46, middle temporal gyrus, mucosa of sigmoid colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLTC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	8.6e-10	-0.43	17:59736463:A:G
Cells Cultured fibroblasts	sqtl	1.1e-04	-0.40	17:59838063:T:G
Adipose Subcutaneous	sqtl	2.3e-04	+0.19	17:59654624:T:C
Artery Tibial	sqtl	1.1e-03	-0.19	17:59689924:C:A
Cells Cultured fibroblasts	eqtl	1.9e-03	-0.07	17:59645912:G:A
Colon Transverse	eqtl	1.1e-02	-0.18	17:60579350:G:A
Thyroid	sqtl	1.4e-02	-0.24	17:59702317:A:G
Brain Anterior cingulate cortex BA24	sqtl	1.5e-02	-0.26	17:59647682:T:G
Artery Tibial	eqtl	2.0e-02	+0.07	17:59691837:A:G
Thyroid	eqtl	2.4e-02	+0.11	17:59395855:G:A
Spleen	eqtl	3.3e-02	+0.36	17:58778351:T:G
Artery Coronary	eqtl	3.6e-02	+0.37	17:60442752:G:A
Lung	sqtl	3.8e-02	+0.29	17:59620847:C:G
Heart Atrial Appendage	eqtl	4.3e-02	-0.20	17:60047472:T:C
Brain Amygdala	eqtl	4.8e-02	-0.92	17:60251285:T:A

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
161963	228.0489	1829
161962	11.4852	1737
208286	0.7384	420
161970	0.6973	328
161969	0.4665	225
161965	0.4565	227

Top tissues by expression

showing 100 of 305 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.67	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.65	gold quality
middle temporal gyrus	UBERON:0002771	99.58	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.57	gold quality
orbitofrontal cortex	UBERON:0004167	99.56	gold quality
postcentral gyrus	UBERON:0002581	99.55	gold quality
corpus epididymis	UBERON:0004359	99.54	gold quality
colonic mucosa	UBERON:0000317	99.52	gold quality
parietal lobe	UBERON:0001872	99.52	gold quality
trabecular bone tissue	UBERON:0002483	99.52	gold quality
substantia nigra pars compacta	UBERON:0001965	99.51	gold quality
visceral pleura	UBERON:0002401	99.43	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.41	gold quality
bronchial epithelial cell	CL:0002328	99.40	gold quality
caput epididymis	UBERON:0004358	99.40	gold quality
cauda epididymis	UBERON:0004360	99.40	gold quality
superior frontal gyrus	UBERON:0002661	99.39	gold quality
superior vestibular nucleus	UBERON:0007227	99.38	gold quality
stromal cell of endometrium	CL:0002255	99.36	gold quality
lateral globus pallidus	UBERON:0002476	99.35	gold quality
entorhinal cortex	UBERON:0002728	99.35	gold quality
pleura	UBERON:0000977	99.34	gold quality
parietal pleura	UBERON:0002400	99.33	gold quality
skin of hip	UBERON:0001554	99.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.31	gold quality
upper leg skin	UBERON:0004262	99.30	gold quality
adrenal tissue	UBERON:0018303	99.29	gold quality
nasal cavity epithelium	UBERON:0005384	99.28	gold quality
tibia	UBERON:0000979	99.25	gold quality
pigmented layer of retina	UBERON:0001782	99.24	gold quality
mammalian vulva	UBERON:0000997	99.23	gold quality
cartilage tissue	UBERON:0002418	99.23	gold quality
retina	UBERON:0000966	99.22	gold quality
renal medulla	UBERON:0000362	99.21	gold quality
placenta	UBERON:0001987	99.21	gold quality
ventricular zone	UBERON:0003053	99.21	gold quality
trigeminal ganglion	UBERON:0001675	99.19	gold quality
epithelium of bronchus	UBERON:0002031	99.18	gold quality
choroid plexus epithelium	UBERON:0003911	99.18	gold quality
endothelial cell	CL:0000115	99.17	gold quality
epithelium of nasopharynx	UBERON:0001951	99.17	gold quality
nasopharynx	UBERON:0001728	99.15	gold quality
bronchus	UBERON:0002185	99.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.12	gold quality
seminal vesicle	UBERON:0000998	99.11	gold quality
ileal mucosa	UBERON:0000331	99.10	gold quality
medulla oblongata	UBERON:0001896	99.08	gold quality
oral cavity	UBERON:0000167	99.06	gold quality
eye	UBERON:0000970	99.04	gold quality
islet of Langerhans	UBERON:0000006	99.03	gold quality
palpebral conjunctiva	UBERON:0001812	99.00	gold quality
ileum	UBERON:0002116	99.00	silver quality
type B pancreatic cell	CL:0000169	98.99	gold quality
subthalamic nucleus	UBERON:0001906	98.99	gold quality
ventral tegmental area	UBERON:0002691	98.99	gold quality
CA1 field of hippocampus	UBERON:0003881	98.99	gold quality
cortical plate	UBERON:0005343	98.98	gold quality
inferior vagus X ganglion	UBERON:0005363	98.98	gold quality
lower lobe of lung	UBERON:0008949	98.95	gold quality
germinal epithelium of ovary	UBERON:0001304	98.94	gold quality
embryo	UBERON:0000922	98.92	gold quality
jejunal mucosa	UBERON:0000399	98.89	gold quality
synovial joint	UBERON:0002217	98.88	gold quality
superficial temporal artery	UBERON:0001614	98.87	gold quality
cranial nerve II	UBERON:0000941	98.85	gold quality
ganglionic eminence	UBERON:0004023	98.85	gold quality
prefrontal cortex	UBERON:0000451	98.84	gold quality
nephron tubule	UBERON:0001231	98.83	gold quality
upper arm skin	UBERON:0004263	98.83	gold quality
colonic epithelium	UBERON:0000397	98.82	gold quality
right frontal lobe	UBERON:0002810	98.82	gold quality
hypothalamus	UBERON:0001898	98.81	gold quality
decidua	UBERON:0002450	98.81	gold quality
smooth muscle tissue	UBERON:0001135	98.79	gold quality
mammary duct	UBERON:0001765	98.79	gold quality
gingiva	UBERON:0001828	98.79	gold quality
midbrain	UBERON:0001891	98.79	gold quality
cardia of stomach	UBERON:0001162	98.77	gold quality
heart right ventricle	UBERON:0002080	98.76	gold quality
nasal cavity mucosa	UBERON:0001826	98.75	gold quality
tongue squamous epithelium	UBERON:0006919	98.75	gold quality
epithelial cell of pancreas	CL:0000083	98.74	gold quality
substantia nigra	UBERON:0002038	98.74	gold quality
mucosa of urinary bladder	UBERON:0001259	98.73	gold quality
occipital lobe	UBERON:0002021	98.73	gold quality
calcaneal tendon	UBERON:0003701	98.73	gold quality
nucleus accumbens	UBERON:0001882	98.72	gold quality
epithelium of mammary gland	UBERON:0003244	98.72	gold quality
endometrium	UBERON:0001295	98.71	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.71	gold quality
dorsal root ganglion	UBERON:0000044	98.68	gold quality
urethra	UBERON:0000057	98.68	gold quality
thoracic mammary gland	UBERON:0005200	98.68	gold quality
mammary gland	UBERON:0001911	98.66	gold quality
pylorus	UBERON:0001166	98.65	gold quality
caudate nucleus	UBERON:0001873	98.65	gold quality
putamen	UBERON:0001874	98.65	gold quality
gingival epithelium	UBERON:0001949	98.65	gold quality
Ammon’s horn	UBERON:0001954	98.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.16

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cerebral cortex	tissue	312.8	medium
Somatosensory cortex	tissue	312.8
Caudate putamen	tissue	307.6
Pons	tissue	306.5
Thalamus	tissue	293.2
Occipital cortex	tissue	289.1
Superior colliculi	tissue	279.1
Frontal cortex	tissue	276.1
Motor cortex	tissue	267.0
Midbrain	tissue	263.7
Putamen	tissue	260.1
Hippocampal formation	tissue	255.8
Retrosplenial and cingulate cortex	tissue	255.5
Spinal cord	tissue	253.6
Medulla oblongata	tissue	250.7
Prefrontal cortex	tissue	250.1
Entorhinal cortex	tissue	249.7
Temporal cortex	tissue	248.4
Retrosplenial cortex	tissue	235.4
Substantia nigra	tissue	232.0
Hypothalamus	tissue	228.4
Locus coeruleus	tissue	223.1
Septum	tissue	218.2
Ventral forebrain	tissue	217.7
Basal ganglia	tissue	214.3	medium
Cerebellum	tissue	213.4	medium
Postcentral gyrus	tissue	211.2
Choroid plexus	tissue	210.4
Insular cortex	tissue	206.9
Periaqueductal gray	tissue	203.8
Nucleus accumbens	tissue	184.8
Olfactory bulb	tissue	181.6
Amygdala	tissue	173.5
Hippocampus	tissue	164.8	medium
Corpus callosum	tissue	160.8
Parathyroid gland	tissue	150.8	high
Retina	tissue	120.8
Placenta	tissue	118.6	high
Rectum	tissue	104.0	medium
Kidney	tissue	102.8	medium
Liver	tissue	100.7	medium
Colon	tissue	97.5	medium
Thyroid gland	tissue	92.2	medium
Epididymis	tissue	90.1	medium
Bone marrow	tissue	84.5	medium
Smooth muscle	tissue	83.5	not detected
Urinary bladder	tissue	81.3	medium
Adipose tissue	tissue	80.4	not detected
Adrenal gland	tissue	79.6	medium
Stomach 1	tissue	74.9	medium
Cervix	tissue	74.2	medium
Prostate	tissue	73.9	medium
Appendix	tissue	73.5	medium
Seminal vesicle	tissue	70.7	medium
Tonsil	tissue	70.4	medium
Skin 1	tissue	67.0	low
Lung	tissue	65.9	medium
Breast	tissue	65.8	medium
Gallbladder	tissue	64.8	medium
Spleen	tissue	64.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Pontine nuclei (263.5), Dorsal hippocampus (255.8), Ventral spinal cord (253.6), Nuclei of the trapezoid body (247.3), Subiculum (245.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

Targeting CLTC by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 167 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.104, missense Z 10.2 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000269122 splits into 9 regions with different missense tolerance; 4 are missense-constrained (≈40% 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
17:59,620,132–59,644,309	24 / 29.8	0.81	no
17:59,644,310–59,666,878	293 / 795.6	0.37	no
17:59,666,879–59,666,930	0 / 19.2	0.00	yes (p 1.2e-05)
17:59,666,931–59,668,827	19 / 35.7	0.53	no
17:59,668,828–59,668,893	0 / 24.3	0.00	yes (p 8.1e-07)
17:59,668,894–59,681,743	160 / 448.2	0.36	yes (p 3.4e-42)
17:59,681,744–59,682,364	50 / 77.2	0.65	no
17:59,682,365–59,683,754	102 / 317.6	0.32	yes (p 1.1e-33)
17:59,683,755–59,693,849	148 / 279.5	0.53	no
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 99.2% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SNU-16 (-3.34), OE33 (-3.266), EFO-21 (-3.221), AML-193 (-3.075), HSC-2 (-2.979), PC-14 (-2.935), KLE (-2.819), HCC1937 (-2.669), NB-4 (-2.615), HCC-78 (-2.566), SCC-4 (-2.56), OE21 (-2.538), MEC-1 (-2.437), BxPC-3 (-2.417), SH-4 (-2.413).

Literature-anchored findings (GeneRIF, showing 40)

• Results indicate that AP-2 is not essential for clathrin-coated vesicle formation at the plasma membrane, but that it is one of several endocytic adaptors required for the uptake of certain cargo proteins. (PMID:12952941)
• neither clathrin nor AP-2 is essential for the internalization of epidermal growth factor (PMID:12960147)
• Clathrin heavy chain phosphorylation and dephosphorylation are involved in TCR internalization; this is a regulatory mechanism linking TCR signaling to endocytosis. (PMID:15067034)
• Data suggest that clathrin heavy chains bound to light chains (LC) a and b contribute to pit formation, but the affinity of LCa-free HC in pits is reduced, and the Ca(2+)- and ATP-mediated control of clathrin function is lost. (PMID:16138905)
• Nuclear CHC is required for the transactivation of p53 target genes and plays a distinct role from clathrin-mediated endocytosis. (PMID:16618797)
• Syt I plays a pivotal role in mediating cAMP- and Ca(2+)-induced endocytosis of NHE3 (but not in inhibition of activity) through cargo recognition of NHE3 and subsequent recruitment of AP2-clathrin assembly required for membrane endocytosis. (PMID:17307723)
• Results establish a role for the retromer complex in retrograde transport of the B-subunit of Shiga toxin, and strongly suggest that clathrin and retromer function in consecutive retrograde sorting steps on early endosomes. (PMID:17550971)
• Nuclear CHC plays a role distinct from clathrin-mediated endocytosis. (PMID:17952123)
• The clathrin inhibitor phenylarsine oxide prevented SubAB entry and BiP cleavage in SubAB-treated Vero, HeLa and N2A cells demonstrating that SubAB internalization is clathrin-dependent. (PMID:18042253)
• cytosolic p53 may participate in the regulation of clathrin-mediated endocytosis to control the correct signaling from EGFR (PMID:18363968)
• The endocytic clathrin machinery can internalize double-membrane vesicles into cells. (PMID:18656476)
• Endocytosis of shiga toxin (Stx) in Ramos cells requires Syk activity and that Syk is recruited to the uptake site of Stx. (PMID:19289168)
• Data compared each paralogue in functional assays of endocytosis and mitosis, and find that CHC17 and CHC22 are functionally equivalent. (PMID:19509056)
• clathrin serving as a regulator of SNX4-dependent transport; upon clathrin release, dynein may bind SNX4 and mediate retrograde movement (PMID:19529763)
• GAK and CHC cooperated in the same pathway and interacted in mitosis to regulate the formation of a functional spindle. (PMID:19654208)
• Structural modeling analyses predict that an Asn1288 residue in CHC is crucial for binding to p53. In fact, substitution of this Asn to Ala of CHC diminished its ability to interact with p53, leading to reduced activity to transactivate p53. (PMID:19766654)
• The assembly efficiency of the various hepatitis delta virus genotypes correlates well with the clathrin heavy chain-binding activity of their HDAg-Ls and coincides with the severity of disease outcome. (PMID:19793827)
• Endocytosis of FcalphaR is clathrin- and dynamin-dependent, but is not regulated by Rab5, and the endocytic motif is not located in the cytoplasmic domain of FcalphaR. (PMID:19859085)
• These data indicate that the endocytic uptake of the clostridial glucosylating toxins involves a dynamin-dependent process that is mainly governed by clathrin. (PMID:20498856)
• the association between aurora A phosphorylation and spindle apparatus; regulation from aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG to mitotic spindles. (PMID:20566684)
• Data show in mammalian cells that the heavy chain of clathrin interacts with Atg16L1 and is involved in the formation of Atg16L1-positive early autophagosome precursors. (PMID:20639872)
• The authors now report that the integrase domain of Gag-Pol is required for the incorporation of clathrin into HIV-1 virions. (PMID:21289110)
• Clathrin is recruited to the mitotic spindle by TACC3 and ch-TOG. Together the complex forms inter-microtubule bridges in kinetochore fibres (PMID:21297582)
• Data suggest that clathrin’s role in intermicrotubule bridging can be fulfilled not only by trimers but also by dimers, and that the membrane trafficking and mitotic functions of clathrin are independent and separable. (PMID:21362119)
• CHC functions as a built-in molecular brake that ensures a tight control of basal NF-kappaB activation and gene expression in unstimulated cells. (PMID:21364927)
• Our findings strongly suggest that clathrin and clathrin-mediated signaling pathways are involved in the inflammatory signal transduction of orbital fibroblasts in Graves ophthalmopathy. (PMID:21917865)
• Postmitotic Golgi reassembly requires the clathrin heavy chain (CHC). (PMID:21965600)
• is required for lamellipodium formation (PMID:22010197)
• Electron tomography reveals Rab6 is essential to the trafficking of trans-Golgi clathrin and COPI-coated vesicles and the maintenance of Golgi cisternal number (PMID:22335553)
• These results indicate that Echovirus 7 is internalized by clathrin-mediated endocytosis. (PMID:22496312)
• Depletion of clathrin heavy chain (CHC)17, but not the CHC22 clathrin isoform, by ribonucleic acid interference (RNAi) induces centrosome amplification and multipolar spindles. (PMID:22891263)
• This study reveals a novel functional role of clathrin-coated structure in GMR signaling and the oncogenesis of JAK2V617F. (PMID:22935703)
• The authors demonstrate that clathrin promotes clustering of the vaccinia virus actin tail nucleator A36 and host N-WASP, which activates actin nucleation through the Arp2/3 complex. (PMID:22980331)
• High clathrin heavy chain expression promotes tumor pancreatic growth and angiogenesis through regulation of HIF-1alpha and VEGF signaling (PMID:23228632)
• SNX9 and CHC function in the same molecular pathway for chromosome alignment and segregation, which is dependent on their direct association. (PMID:23861900)
• clathrin interacts with Rab5 and plays a fundamental role in the entry and intracellular survival of B. abortus via interaction with lipid rafts and actin rearrangement (PMID:23940042)
• Clathrin and caveolin-1 have a role in docking of SMAD4 at the cell membrane. (PMID:24211445)
• These data indicate that clathrin is required for the function of AP-1- and GGA-coated carriers at the trans-Golgi network but may be dispensable for outward traffic en route to the plasma membrane. (PMID:24407285)
• clathrin-mediated and caveolae-mediated endocytosis of VE-cad contribute to lipopolysaccharide-induced vascular hyperpermeability. (PMID:25180771)
• autophagy contributed to Cx31.1 degradation, and clathrin might be involved in the autophagy of Cx31.1. (PMID:25388970)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cltc	ENSMUSG00000047126
rattus_norvegicus	Cltc	ENSRNOG00000004291
drosophila_melanogaster	Chc	FBGN0000319
caenorhabditis_elegans		WBGENE00011867

Paralogs (2): CLTCL1 (ENSG00000070371), CLHC1 (ENSG00000162994)

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
Bos taurus	P49951	99.9%	Diamond
Oryza sativa Japonica Group	Q2QYW2	99.9%	Diamond
Arabidopsis thaliana	Q0WNJ6	97.0%	Diamond
Dictyostelium discoideum	P25870	58.5%	Diamond
Schizosaccharomyces pombe 972h-	Q10161	55.1%	Diamond
Saccharomyces cerevisiae S288C	P22137	52.3%	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
LINC01476	ncRNA	101927728
DHX40	protein-coding	79665
MIR21	ncRNA	406991
PTRH2	protein-coding	51651
VMP1	protein-coding	81671
TUBD1	protein-coding	51174

Protein

Protein identifiers

Clathrin heavy chain 1 — Q00610 (reviewed: Q00610)

Alternative names: Clathrin heavy chain on chromosome 17

All UniProt accessions (21): A0A087WVQ6, A0A8V8TQ14, A0A8V8TQ18, A0A8V8TQK1, A0A8V8TQK3, A0A8V8TQK7, A0A8V8TR47, A0A8V8TRE8, A0A8V8TRF0, A0AAQ5BHN4, A0AAQ5BHN6, Q00610, A0AAQ5BHN7, A0AAQ5BHT1, A0AAQ5BHT6, A0AAQ5BHU5, J3KRF5, J3KS13, J3KTN1, J3QL20, K7EJJ5

UniProt curated annotations — full annotation on UniProt →

Function. Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. Plays a role in early autophagosome formation. Interaction with DNAJC6 mediates the recruitment of HSPA8 to the clathrin lattice and creates local destabilization of the lattice promoting uncoating.

Subunit / interactions. Clathrin triskelions, composed of 3 heavy chains and 3 light chains, are the basic subunits of the clathrin coat. In the presence of light chains, hub assembly is influenced by both the pH and the concentration of calcium. Interacts with HIP1. Interacts with DENND1A, DENND1B and DENND1C. May interact with OCRL. Interacts with ERBB2. Interacts with FKBP6. Interacts with CKAP5 and TACC3 forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; the complex implicates clathrin triskelions; TACC3 and CLTC are proposed to form a composite microtubule interaction surface. Interacts with ATG16L1 (via N-terminus). Interacts with RFTN1; the interaction occurs in response to pathogens. Interacts with USP2 isoform 4. Interacts with TMEM106B (via N-terminus). Interacts with DNAJC6; this interaction produces a local change in heavy-chain contacts, creating a detectable global distortion of the clathrin coat and leads to the recruitment of HSPA8.

Subcellular location. Cytoplasmic vesicle membrane. Membrane. Coated pit. Melanosome. Cytoplasm. Cytoskeleton. Spindle.

Disease relevance. Intellectual developmental disorder, autosomal dominant 56 (MRD56) [MIM:617854] A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal seven-bladed beta-propeller is formed by WD40-like repeats, and projects inward from the polyhedral outer clathrin coat. It constitutes a major protein-protein interaction node.

Similarity. Belongs to the clathrin heavy chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q00610-1	1	yes
Q00610-2	2

RefSeq proteins (2): NP_001275582, NP_004850* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000547	Clathrin_H-chain/VPS_repeat	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR015348	Clathrin_H-chain_linker_core	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR016025	Clathrin_H-chain_N	Homologous_superfamily
IPR016341	Clathrin_heavy_chain	Family
IPR022365	Clathrin_H-chain_propeller_rpt	Repeat
IPR055358	CHCR	Repeat

Pfam: PF00637, PF01394, PF09268, PF13838

UniProt features (118 total): strand 27, modified residue 18, mutagenesis site 17, region of interest 16, helix 9, sequence variant 8, turn 7, repeat 7, sequence conflict 5, splice variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
9C0Y	Clathrin terminal domain complexed with Pitstop 2c	X-RAY DIFFRACTION	1.4
9C0Z	Clathrin terminal domain complexed with pitstop 2d	X-RAY DIFFRACTION	1.51
6E4L	The structure of the N-terminal domain of human clathrin heavy chain 1 (nTD) in complex …	X-RAY DIFFRACTION	1.6
4G55	Clathrin terminal domain complexed with pitstop 2	X-RAY DIFFRACTION	1.69
2XZG	Clathrin Terminal Domain Complexed with Pitstop 1	X-RAY DIFFRACTION	1.7
7BN2	Clathrin heavy chain N-terminal domain bound to Non structured protein 3 from Eastern …	X-RAY DIFFRACTION	1.97
7BN1	Clathrin heavy chain N-terminal domain complexed with peptide from Protein mu-NS of …	X-RAY DIFFRACTION	1.97
6QNN	CLATHRIN HEAVY CHAIN N-TERMINAL DOMAIN BOUND TO GTSE1 LIDL MOTIF	X-RAY DIFFRACTION	2.03
7ZX4	Clathrin N-terminal domain in complex with a HURP phospho-peptide	X-RAY DIFFRACTION	2.08
6QNP	CLATHRIN HEAVY CHAIN N-TERMINAL DOMAIN BOUND TO GTSE1 LIDL MOTIF	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00610-F1	75.62	0.08

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutational cancer driver genes, Disease related genes, Potential drug targets, Human disease related genes, Mental and behavioural disorders, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): endosomes; lysosomes; centriolar satellite; cytosol; mid piece; mitotic spindle

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.

Post-translational modifications (18)

Type	Positions
N-acetylalanine	2
Phosphoserine	67, 1167, 1229, 1494
Phosphothreonine	105, 394
Phosphotyrosine	184, 634, 899, 1206, 1477, 1487
N6-succinyllysine	737, 1441
N6-acetyllysine	856, 1441, 1501

Mutagenesis-validated functional residues (17)

Position	Phenotype
65	disrupts spindle localization.
67	disrupts spindle localization.
87	disrupts spindle localization.
89	disrupts spindle localization.
96	disrupts spindle localization.
98	disrupts spindle localization.
444	disrupts spindle localization; when associated with e-445, e-500 e-506 and e-507.
445	disrupts spindle localization; when associated with e-444, e-500, e-506 and e-507.
480–484	disrupts spindle localization and interaction with tacc3.
481	disrupts spindle localization; when associated with e-487, e-500, e-506 and e-507.
487	disrupts spindle localization; when associated with e-481, e-500, e-506 and e-507.
500	disrupts spindle localization; when associated with e-444, e-445, e-506 and e-507.
500	disrupts spindle localization; when associated with e-481, e-487, e-506 and e-507.
506	disrupts spindle localization; when associated with e-444, e-445, e-500 and e-507.
506	disrupts spindle localization; when associated with e-481, e-487, e-500 and e-507.
507	disrupts spindle localization; when associated with e-444, e-445, e-500 and e-506.
507	disrupts spindle localization; when associated with e-481, e-487, e-500 and e-506.

Function

Pathways and Gene Ontology

Reactome pathways

17 curated (TAS) of 50; 9 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

50 pathways:

ID	Pathway	Evidence
R-HSA-9700645	ALK mutants bind TKIs ⚕	curated
R-HSA-168275	Entry of Influenza Virion into Host Cell via Endocytosis ⚕	curated
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-3928665	EPH-ephrin mediated repulsion of cells	curated
R-HSA-196025	Formation of annular gap junctions	curated
R-HSA-190873	Gap junction degradation	curated
R-HSA-432722	Golgi Associated Vesicle Biogenesis	curated
R-HSA-8964038	LDL clearance	curated
R-HSA-432720	Lysosome Vesicle Biogenesis	curated
R-HSA-2132295	MHC class II antigen presentation	curated
R-HSA-9013420	RHOU GTPase cycle	curated
R-HSA-9013424	RHOV GTPase cycle	curated
R-HSA-8866427	VLDLR internalisation and degradation	curated
R-HSA-5140745	WNT5A-dependent internalization of FZD2, FZD5 and ROR2	curated
R-HSA-5099900	WNT5A-dependent internalization of FZD4	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-168255	Influenza Infection ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-422475	Axon guidance	—
R-HSA-3858494	Beta-catenin independent WNT signaling	—
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	—
R-HSA-190828	Gap junction trafficking	—
R-HSA-157858	Gap junction trafficking and regulation	—
R-HSA-168256	Immune System	—
R-HSA-373760	L1CAM interactions	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-9675108	Nervous system development	—
R-HSA-4086400	PCP/CE pathway	—
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance	—
R-HSA-8964043	Plasma lipoprotein clearance	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-437239	Recycling pathway of L1	electronic
R-HSA-177504	Retrograde neurotrophin signalling	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-187037	Signaling by NTRK1 (TRKA)	—
R-HSA-166520	Signaling by NTRKs	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—
R-HSA-195721	Signaling by WNT	—
R-HSA-382551	Transport of small molecules	—
R-HSA-5653656	Vesicle-mediated transport	—
R-HSA-199992	trans-Golgi Network Vesicle Budding	—

MSigDB gene sets: 610 (showing top): GGGACCA_MIR133A_MIR133B, REACTOME_RETROGRADE_NEUROTROPHIN_SIGNALLING, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, LU_IL4_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOBP_TRANSITION_METAL_ION_TRANSPORT, LFA1_Q6, CGGAARNGGCNG_UNKNOWN, MORF_CDK2, HSIAO_HOUSEKEEPING_GENES, GOBP_OSTEOBLAST_DIFFERENTIATION, KEGG_LYSOSOME

GO Biological Process (19): mitotic cell cycle (GO:0000278), osteoblast differentiation (GO:0001649), intracellular protein transport (GO:0006886), receptor-mediated endocytosis (GO:0006898), autophagy (GO:0006914), receptor internalization (GO:0031623), transferrin transport (GO:0033572), retrograde transport, endosome to Golgi (GO:0042147), clathrin coat assembly (GO:0048268), cell division (GO:0051301), regulation of mitotic spindle organization (GO:0060236), clathrin coat disassembly (GO:0072318), clathrin-dependent endocytosis (GO:0072583), amyloid-beta clearance by transcytosis (GO:0150093), negative regulation of hyaluronan biosynthetic process (GO:1900126), negative regulation of protein localization to plasma membrane (GO:1903077), mitotic spindle organization (GO:0007052), chromosome segregation (GO:0007059), vesicle-mediated transport (GO:0016192)

GO Molecular Function (9): RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), structural molecule activity (GO:0005198), protein kinase binding (GO:0019901), clathrin light chain binding (GO:0032051), low-density lipoprotein particle receptor binding (GO:0050750), disordered domain specific binding (GO:0097718), ubiquitin-specific protease binding (GO:1990381), protein binding (GO:0005515)

GO Cellular Component (33): lysosome (GO:0005764), endosome (GO:0005768), spindle (GO:0005819), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), clathrin coat (GO:0030118), clathrin coat of trans-Golgi network vesicle (GO:0030130), clathrin coat of coated pit (GO:0030132), clathrin-coated vesicle (GO:0030136), clathrin-coated endocytic vesicle membrane (GO:0030669), trans-Golgi network membrane (GO:0032588), protein-containing complex (GO:0032991), endolysosome membrane (GO:0036020), melanosome (GO:0042470), clathrin-coated endocytic vesicle (GO:0045334), extracellular exosome (GO:0070062), clathrin complex (GO:0071439), mitotic spindle (GO:0072686), extracellular vesicle (GO:1903561), mitotic spindle microtubule (GO:1990498), trans-Golgi network (GO:0005802), kinetochore microtubule (GO:0005828), clathrin-coated pit (GO:0005905), endomembrane system (GO:0012505), membrane coat (GO:0030117), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), photoreceptor ribbon synapse (GO:0098684), presynaptic endocytic zone membrane (GO:0098835), postsynaptic endocytic zone (GO:0098843), glutamatergic synapse (GO:0098978)

Reactome top-level categories

14 top-level categories:

Category	Pathways
trans-Golgi Network Vesicle Budding	2
PCP/CE pathway	2
Plasma lipoprotein clearance	2
RHO GTPase cycle	2
Signaling by ALK in cancer	2
Influenza Infection	1
Signaling by NTRK1 (TRKA)	1
Gap junction trafficking	1
Gap junction degradation	1
Adaptive Immune System	1
EPH-Ephrin signaling	1
L1CAM interactions	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1

GO top-level categories

showing 60 of 79 GO namespaces:

Category	Terms
protein transport	2
receptor-mediated endocytosis	2
cellular process	2
cellular anatomical structure	2
clathrin coat	2
cell cycle	1
mitotic nuclear division	1
ossification	1
cell differentiation	1
intracellular protein localization	1
intracellular transport	1
endocytosis	1
vesicle-mediated transport	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
iron ion transport	1
endosomal transport	1
cytosolic transport	1
protein-containing complex assembly	1
mitotic spindle organization	1
regulation of spindle organization	1
vesicle uncoating	1
clathrin-dependent endocytosis	1
transcytosis	1
amyloid-beta clearance	1
negative regulation of macromolecule biosynthetic process	1
hyaluronan biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
regulation of hyaluronan biosynthetic process	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
negative regulation of protein localization to cell periphery	1
negative regulation of protein localization to membrane	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell cycle process	1
transport	1
nucleic acid binding	1
RNA binding	1
molecular_function	1
kinase binding	1
clathrin binding	1
lipoprotein particle receptor binding	1
protein domain specific binding	1
protease binding	1
binding	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
microtubule cytoskeleton	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1
cell-substrate junction	1
membrane coat	1
Golgi apparatus	1
trans-Golgi network transport vesicle membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 31 of 61 annotations. The rest are phylogenetic / computational / electronic (IEA).

31 experimentally-supported GO terms:

GO term	NS	Evidence
amyloid-beta clearance by transcytosis	BP	mutant phenotype
clathrin coat assembly	BP	mutant phenotype
clathrin-dependent endocytosis	BP	mutant phenotype
mitotic cell cycle	BP	mutant phenotype
negative regulation of hyaluronan biosynthetic process	BP	direct assay
negative regulation of protein localization to plasma membrane	BP	mutant phenotype
osteoblast differentiation	BP	high-throughput assay
receptor internalization	BP	mutant phenotype
receptor-mediated endocytosis	BP	mutant phenotype
regulation of mitotic spindle organization	BP	mutant phenotype
retrograde transport, endosome to Golgi	BP	mutant phenotype
transferrin transport	BP	mutant phenotype
clathrin coat	CC	mutant phenotype
clathrin complex	CC	direct assay
clathrin-coated vesicle	CC	direct assay
endosome	CC	direct assay
extracellular exosome	CC	high-throughput assay
extracellular vesicle	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
lysosome	CC	direct assay
membrane	CC	high-throughput assay
mitotic spindle	CC	direct assay
mitotic spindle microtubule	CC	direct assay
protein-containing complex	CC	direct assay
spindle	CC	direct assay
RNA binding	MF	high-throughput assay
clathrin light chain binding	MF	physical interaction
disordered domain specific binding	MF	physical interaction
double-stranded RNA binding	MF	direct assay
low-density lipoprotein particle receptor binding	MF	physical interaction
ubiquitin-specific protease binding	MF	physical interaction

Protein interactions and networks

STRING

showing 16 of 3,626 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLTC	CLTA	P09496	882
CLTC	EPN2	O95208	848
CLTC	EPN3	Q9H201	847
CLTC	EEA1	Q15075	844
CLTC	CLTB	P09497	833
CLTC	AP2A1	O95782	826
CLTC	DNM1	Q05193	823
CLTC	ASPSCR1	Q9BZE9	815
CLTC	AP2M1	P20172	812
CLTC	RCC1	P18754	809
CLTC	RAB35	Q15286	771
CLTC	RAB5A	P20339	761
CLTC	DNAJC6	O75061	757
CLTC	TFE3	P19532	755
CLTC	DENND1A	Q8TEH3	754
CLTC	CLINT1	Q14677	754

IntAct

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

showing 30 of 73 partners by confidence:

Partner	Interaction type	MIscore	Records
OCRL	physical association	0.800	5
PAAT	association	0.740	3
TNK2	direct interaction	0.700	3
ARRB2	direct interaction	0.680	5
CLTA	physical association	0.670	1
DLGAP5	physical association	0.650	4
MYB	physical association	0.620	1
TOM1L1	physical association	0.540	4
IKBKB	proximity	0.540	2
ARRB1	colocalization	0.490	1
HIP1	proximity	0.480	1
ADRA1A	physical association	0.460	2
BCL11A	direct interaction	0.440	1
M3	direct interaction	0.440	1
MAU2	direct interaction	0.440	1
MITF	direct interaction	0.440	1
PIK3C2B	direct interaction	0.440	1
SH3D19	direct interaction	0.440	1
TMEM94	direct interaction	0.440	1
LAS2	physical association	0.400	1
NDRG1	physical association	0.400	1
PTCHD3	physical association	0.400	1
YWHAZ	physical association	0.400	1
EP300	physical association	0.370	1
GCNT1	physical association	0.370	1
PPP1CA	physical association	0.370	1
QARS1	physical association	0.370	1
XRCC6	physical association	0.370	1
CLTB	association	0.350	1
ERBB2	association	0.350	1

BioGRID (1,042 interactions; top human partners by supporting records in a sample of 600 records): CLTA (Co-fractionation; 7 records), HIP1 (Affinity Capture-MS; 7 records), CLTB (Affinity Capture-MS; 6 records), ARF6 (Affinity Capture-Western; 5 records), C10orf88 (Affinity Capture-MS; 4 records), HSPA8 (Affinity Capture-MS; 4 records), MYO6 (Affinity Capture-MS; 4 records), PICALM (Affinity Capture-MS; 4 records), PTPN23 (Affinity Capture-MS; 4 records), TNK2 (Affinity Capture-MS; 4 records), FBXW11 (Affinity Capture-MS; 3 records), GAK (Affinity Capture-MS; 3 records), HGS (Affinity Capture-Western; 3 records), OCRL (Affinity Capture-Western; 3 records), STAMBPL1 (Affinity Capture-MS; 3 records)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
PICALM	up-regulates	CLTC	binding
ATG16L1	up-regulates	CLTC	binding
CLTC	“form complex”	“AP-2/clathrin vescicle”	binding
CLTC	“form complex”	“AP-3/clathrin vescicle”	binding
CLTC	“form complex”	“AP-1/clathrin vescicle”	binding
SRC	up-regulates	CLTC	phosphorylation
GAK	“up-regulates activity”	CLTC	phosphorylation

Protein complexes (CORUM) (5)

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

5 complexes by size:

Complex	Subunits	Members
PI4K2A-WASH complex	14	ARHGEF2, CAPZB, DOCK7, FKBP15, NEDD4, WASHC2A, WASHC4, WASHC5, AP3B1, ARHGEF1, CAPZA1, CLTC, DNM2, PI4K2A
ACAP1-CLTC-SLC2A4 complex	3	ACAP1, CLTC, SLC2A4
p532-Clathrin-HSP70 complex	3	CLTC, HERC1, HSPA1A
★ CLTC-SYK complex	2	CLTC, SYK
CLTC-PI4K2A complex	2	CLTC, PI4K2A

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
RIP-mediated NFkB activation via ZBP1	8	92.7×	3e-12
TRAF6 mediated NF-kB activation	8	63.0×	3e-11
TNFR1-induced NF-kappa-B signaling pathway	9	52.1×	2e-11
TAK1-dependent IKK and NF-kappa-B activation	9	46.6×	2e-11
TNF signaling	6	43.8×	2e-07
TNFR1-induced proapoptotic signaling	5	37.9×	5e-06
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	6	36.9×	5e-07
Regulation of TNFR1 signaling	8	30.9×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	9	114.9×	8e-15
canonical NF-kappaB signal transduction	14	77.7×	8e-21
tumor necrosis factor-mediated signaling pathway	9	45.1×	7e-11
negative regulation of canonical NF-kappaB signal transduction	8	20.8×	7e-07
negative regulation of autophagy	5	19.6×	4e-04
cellular response to tumor necrosis factor	7	17.4×	1e-05
positive regulation of canonical NF-kappaB signal transduction	14	15.4×	7e-11
inflammatory response	12	6.8×	1e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — BRCA, CCRCC, CHOL, HCC, UTUC.

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 CLTC: 1,292 ClinVar records (139 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

1,292 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	68
Likely pathogenic	71
Uncertain significance	548
Likely benign	508
Benign	21

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 139 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
183428	NM_016077.5(PTRH2):c.269_270del (p.Ala90fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
816974	NM_004859.4(CLTC):c.187C>T (p.Arg63Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2693304	NM_004859.4(CLTC):c.4791del (p.Tyr1598fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1676904	NM_004859.4(CLTC):c.3931C>T (p.Arg1311Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2431512	NM_004859.4(CLTC):c.3493C>T (p.Arg1165Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2572399	NM_004859.4(CLTC):c.3647TGT[1] (p.Leu1217del)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
811442	NC_000017.11:g.59664787del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
208688	NM_004859.4(CLTC):c.2737_2738dup (p.Asp913fs)	Pathogenic	criteria provided, single submitter	2
488420	NM_004859.4(CLTC):c.4663C>T (p.Gln1555Ter)	Pathogenic	criteria provided, single submitter	2
489191	NM_004859.4(CLTC):c.2050C>T (p.Gln684Ter)	Pathogenic	criteria provided, single submitter	1
489236	NM_004859.4(CLTC):c.769C>T (p.Gln257Ter)	Pathogenic	criteria provided, single submitter	1
489268	NM_004859.4(CLTC):c.2560A>T (p.Arg854Ter)	Pathogenic	criteria provided, single submitter	1
504135	NM_004859.4(CLTC):c.3637GCT[1] (p.Ala1214del)	Pathogenic	criteria provided, single submitter	1
521468	NM_004859.4(CLTC):c.4420G>T (p.Glu1474Ter)	Pathogenic	criteria provided, single submitter	1
524157	NM_004859.4(CLTC):c.4568dup (p.Ser1524fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CLTC’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; 35 predictions of 2,155):

Position(s)	Effect	Δscore	Sites
17:59644274–59644275	acceptor_loss	1.0000	6
17:59647549	donor_gain	1.0000
17:59648402–59648403	donor_loss	1.0000	5
17:59655852–59655853	acceptor_loss	1.0000	3
17:59656028–59656029	donor_loss	1.0000	5
17:59660383	acceptor_gain	1.0000
17:59660390	acceptor_loss	1.0000	2
17:59660589–59660590	donor_loss	1.0000	5
17:59664786	acceptor_loss	1.0000	2
17:59664910–59664911	donor_loss	1.0000	5

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 11,105 scored), across 1,218 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M73	9	0.970	0.999
M996	9	0.954	1.000
M295	9	0.924	0.989
M1159	9	0.882	0.978
M604	9	0.872	0.991
M181	9	0.842	0.999
M1041	9	0.829	0.970
D259	8	1.000	1.000
F260	8	0.998	1.000
F304	8	0.998	1.000
D779	8	0.998	1.000
F91	8	0.997	1.000
F1018	8	0.997	1.000
N1026	8	0.997	1.000
F418	8	0.996	0.999
D821	8	0.996	0.999
D1051	8	0.996	0.999
F27	8	0.995	1.000
H197	8	0.995	1.000
F201	8	0.993	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.2e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	6.05e-05
Kidney Chromophobe (TCGA)	unfavorable	0.00034

Disease associations

OMIM: gene MIM:118955 | disease phenotypes: MIM:617854, MIM:616263, MIM:609942

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
intellectual disability, autosomal dominant 56	Strong	Autosomal dominant	5
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (7): intellectual disability, autosomal dominant 56 (MONDO:0030922), autosomal dominant non-syndromic intellectual disability (MONDO:0015802), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 1 (MONDO:8000012), Noonan syndrome 3 (MONDO:0012371), undetermined early-onset epileptic encephalopathy (MONDO:0018614)

Orphanet (4): Autosomal dominant non-syndromic intellectual disability (Orphanet:178469), Infantile multisystem neurologic-endocrine-pancreatic disease (Orphanet:456312), Noonan syndrome (Orphanet:648), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 79 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000338	Hypomimic face
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Diminished deep tendon reflex
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0002020	Gastroesophageal reflux
HP:0002059	Cerebral atrophy
HP:0002061	Lower limb spasticity
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002133	Status epilepticus
HP:0002136	Broad-based gait
HP:0002188	Delayed CNS myelination
HP:0002312	Clumsiness
HP:0002317	Unsteady gait
HP:0002375	Hypokinesia
HP:0002376	Developmental regression
HP:0002385	Paraparesis
HP:0002421	Poor head control
HP:0002509	Limb hypertonia
HP:0002521	Hypsarrhythmia
HP:0002540	Inability to walk
HP:0003593	Infantile onset

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C537847	Noonan syndrome 3 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3108634 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

18 measured of 18 human assays (19 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM
CHEMBL3110181	IC50	6900 nM
CHEMBL3110178	IC50	10000 nM
CHEMBL3110180	IC50	10000 nM
CHEMBL3110188	IC50	12000 nM
CHEMBL3110184	IC50	15000 nM
CHEMBL3110179	IC50	15000 nM
CHEMBL3110183	IC50	16000 nM
CHEMBL3110174	IC50	18000 nM
CHEMBL3110182	IC50	22000 nM
CHEMBL3110161	IC50	80000 nM
CHEMBL3110185	IC50	100000 nM
CHEMBL3110186	IC50	100000 nM
CHEMBL3110177	IC50	100000 nM
CHEMBL3110162	IC50	100000 nM
CHEMBL3110160	IC50	100000 nM
CHEMBL3110158	IC50	100000 nM
CHEMBL3110159	IC50	120000 nM

ChEMBL bioactivities

7 potent at pChembl≥5 of 20 total, top 7 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.72	Kd	18.95	nM	CHEMBL3752910
7.72	ED50	18.95	nM	CHEMBL3752910
7.67	Kd	21.35	nM	CHEMBL5653589
7.67	ED50	21.35	nM	CHEMBL5653589
5.16	IC50	6900	nM	CHEMBL3110181
5.00	IC50	1e+04	nM	CHEMBL3110178
5.00	IC50	1e+04	nM	CHEMBL3110180

PubChem BioAssay actives

5 with measured affinity, of 40 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148092: Binding affinity to human CLTC incubated for 45 mins by Kinobead based pull down assay	kd	0.0190	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148092: Binding affinity to human CLTC incubated for 45 mins by Kinobead based pull down assay	kd	0.0214	uM
potassium 2-benzyl-1,3-dioxobenzo[de]isoquinoline-5-sulfonate	1065873: Inhibition of recombinant GST-tagged clathrin heavy chain (unknown origin) after 1 hr by ELISA	ic50	6.9000	uM
potassium 2-[(4-chlorophenyl)methyl]-1,3-dioxobenzo[de]isoquinoline-5-sulfonate	1065873: Inhibition of recombinant GST-tagged clathrin heavy chain (unknown origin) after 1 hr by ELISA	ic50	10.0000	uM
potassium 2-[(2-aminophenyl)methyl]-1,3-dioxobenzo[de]isoquinoline-5-sulfonate	1065873: Inhibition of recombinant GST-tagged clathrin heavy chain (unknown origin) after 1 hr by ELISA	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects cotreatment, affects expression, decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
Benzene	increases expression	2
Fluorouracil	affects cotreatment, affects response to substance, affects reaction, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
salinomycin	decreases expression	1
arsenite	decreases reaction, affects binding	1
methylparaben	increases expression	1
sodium arsenite	increases expression	1
yessotoxin	increases expression	1
glycidamide	increases expression	1
deguelin	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
nilotinib	affects cotreatment, affects expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
jinfukang	decreases expression	1
PP242	decreases expression	1
Irinotecan	affects cotreatment, affects response to substance, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3110375	Binding	Inhibition of recombinant GST-tagged clathrin heavy chain (unknown origin) at 100 uM after 1 hr by ELISA	Development of 1,8-naphthalimides as clathrin inhibitors. — *J Med Chem*

Cellosaurus cell lines

23 cell lines: 23 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1092	BT-549	Cancer cell line	Female
CVCL_1259	HCC1954	Cancer cell line	Female
CVCL_4W93	HCC1954-Luc	Cancer cell line	Female
CVCL_5711	BJAB	Cancer cell line	Female
CVCL_5948	11-9-1-4	Cancer cell line	Female
CVCL_B3MM	HCC1954/TDR	Cancer cell line	Female
CVCL_F1N2	HyCyte BT-549 KO-hARTN	Cancer cell line	Female
CVCL_F1N3	HyCyte BT-549 KO-hBAD	Cancer cell line	Female
CVCL_F1N4	HyCyte BT-549 KO-hCD70	Cancer cell line	Female
CVCL_F1N5	HyCyte BT-549 KO-hEOMES	Cancer cell line	Female

Clinical trials (associated diseases)

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

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	Phase 2/3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	Phase 1/2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	Early Phase 1	TERMINATED	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders
NCT02862808	Not specified	COMPLETED	Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study
NCT02881333	Not specified	UNKNOWN	Various Type of Genetic Events in Patients With Intellectual Disability
NCT02889068	Not specified	COMPLETED	Targeted Next Generation Sequencing and Intellectual Disability
NCT02914951	Not specified	ENROLLING_BY_INVITATION	Cognitive-Behavioral Therapy for Irritability in Children With Autism Spectrum Disorder and Intellectual Disability
NCT02919826	Not specified	COMPLETED	Dialectical Behaviour Group Therapy for Adults With Intellectual Disabilities
NCT02934854	Not specified	WITHDRAWN	Biomarker for Creatine Deficiency Syndromes (BioCDS)
NCT03033797	Not specified	UNKNOWN	Augmentative and Alternative Communication in Games With Virtual Reality in Intellectual Disabilities
NCT03135236	Not specified	COMPLETED	Parents as the Primary Sexuality Educators for Their Young Adults With Down Syndrome

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CLTC across ~30M SureChEMBL compounds — explore on Sugi Predict.