CLTA

Summary

CLTA (clathrin light chain A, HGNC:2090) is a protein-coding gene on chromosome 9p13.3, encoding Clathrin light chain A (P09496). Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.

Clathrin is a large, soluble protein composed of heavy and light chains. It functions as the main structural component of the lattice-type cytoplasmic face of coated pits and vesicles which entrap specific macromolecules during receptor-mediated endocytosis. This gene encodes one of two clathrin light chain proteins which are believed to function as regulatory elements. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 8 and 12.

Source: NCBI Gene 1211 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 40 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001833

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2090
Approved symbol	CLTA
Name	clathrin light chain A
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Lca
Ensembl gene	ENSG00000122705
Ensembl biotype	protein_coding
OMIM	118960
Entrez	1211

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 nonsense_mediated_decay

ENST00000242285, ENST00000345519, ENST00000396603, ENST00000464497, ENST00000466396, ENST00000470744, ENST00000493185, ENST00000540080, ENST00000869064, ENST00000869065, ENST00000869066, ENST00000938561, ENST00000950945

RefSeq mRNA: 10 — MANE Select: NM_001833 NM_001076677, NM_001184760, NM_001184761, NM_001184762, NM_001311203, NM_001311204, NM_001311205, NM_001311206, NM_001833, NM_007096

CCDS: CCDS43802, CCDS55306, CCDS55307, CCDS6600, CCDS6601, CCDS83364

Canonical transcript exons

ENST00000345519 — 5 exons

Exon	Start	End
ENSE00000548503	36198979	36199096
ENSE00000833083	36197551	36197588
ENSE00001841709	36190921	36191273
ENSE00001878603	36211603	36212059
ENSE00003602224	36204068	36204179

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 328.5704 / max 1905.7424, expressed in 1828 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96675	317.1641	1828
96674	11.4063	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	99.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.17	gold quality
epithelium of bronchus	UBERON:0002031	99.13	gold quality
parotid gland	UBERON:0001831	99.12	gold quality
bronchus	UBERON:0002185	99.12	gold quality
bronchial epithelial cell	CL:0002328	99.10	gold quality
pons	UBERON:0000988	99.08	gold quality
adult organism	UBERON:0007023	99.03	gold quality
inferior olivary complex	UBERON:0002127	98.99	gold quality
postcentral gyrus	UBERON:0002581	98.95	gold quality
orbitofrontal cortex	UBERON:0004167	98.95	gold quality
type B pancreatic cell	CL:0000169	98.92	gold quality
substantia nigra pars compacta	UBERON:0001965	98.92	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.92	gold quality
mucosa of transverse colon	UBERON:0004991	98.92	gold quality
superior vestibular nucleus	UBERON:0007227	98.92	gold quality
parietal lobe	UBERON:0001872	98.91	gold quality
superior frontal gyrus	UBERON:0002661	98.88	gold quality
medulla oblongata	UBERON:0001896	98.87	gold quality
middle temporal gyrus	UBERON:0002771	98.86	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.85	gold quality
epithelium of nasopharynx	UBERON:0001951	98.85	gold quality
nasal cavity mucosa	UBERON:0001826	98.84	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.84	gold quality
colonic mucosa	UBERON:0000317	98.81	gold quality
inferior vagus X ganglion	UBERON:0005363	98.81	gold quality
cervix squamous epithelium	UBERON:0006922	98.81	gold quality
placenta	UBERON:0001987	98.80	gold quality
ventral tegmental area	UBERON:0002691	98.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.79	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	122.21
E-HCAD-10	yes	51.16
E-MTAB-6678	yes	11.04
E-HCAD-13	no	1851.39
E-CURD-88	no	3.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting CLTA, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-582-5P	99.47	70.79	2635

Literature-anchored findings (GeneRIF, showing 12)

• Human Rhinovirus 2 uses clathrin-mediated endocytosis to infect cells (PMID:12692238)
• 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)
• in mammalian cells CLCs function in intracellular membrane trafficking by acting as recruitment proteins for HIP1R, enabling HIP1R to regulate actin assembly on clathrin-coated structures (PMID:18165318)
• Data show that MAD2B interacts with CLTA during the G2/M phase of the cell cycle and that depletion of MAD2B leads to a marked increase in the percentage of misaligned chromosomes and a redistribution of CLTA during mitosis. (PMID:21152103)
• upon ligand activation, CysLT(1)R is tyrosine-phosphorylated and released from heterodimers with CysLT(2)R and, subsequently, internalizes from the plasma membrane to the nuclear membrane in a clathrin-, arrestin-3-, and Rab-5-dependent manner (PMID:21203429)
• IGF1R internalization and co-localization with clathrin and CAV1 upon ligand binding, as well as the status of the IGF1R pathway, cellular proliferation, and the apoptosis of interfered and inhibited Ewing’s sarcoma, were analyzed. (PMID:21611203)
• Upon receptor activation, prostate alpha1A-adrenoceptors bind clathrin LCA. (PMID:23460120)
• Data indicate that clathrin-mediated endocytosis of proto-oncogene protein erbB-3 (ErbB3) is depending on epsin-1. (PMID:26975582)
• There is coordinated action of myosin VI and CLCa at the apical surface where these proteins are essential for fission of clathrin-coated pits. Myosin VI and Huntingtin-interacting protein 1-related protein (Hip1R) are mutually exclusive interactors with CLCa, and suggest a model for the sequential function of myosin VI and Hip1R in actin-mediated clathrin-coated vesicle budding. (PMID:31672988)
• GRK2-mediated receptor phosphorylation and Mdm2-mediated beta-arrestin2 ubiquitination drive clathrin-mediated endocytosis of G protein-coupled receptors. (PMID:32962859)
• Role of Clathrin Light Chains in Regulating Invadopodia Formation. (PMID:33672612)
• Clathrin light chain A facilitates small extracellular vesicle uptake to promote hepatocellular carcinoma progression. (PMID:37354358)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clta	ENSDARG00000045618
mus_musculus	Clta	ENSMUSG00000028478
rattus_norvegicus	Clta	ENSRNOG00000014635
drosophila_melanogaster	Clc	FBGN0024814
caenorhabditis_elegans		WBGENE00020246

Paralogs (1): CLTB (ENSG00000175416)

Protein

Protein identifiers

Clathrin light chain A — P09496 (reviewed: P09496)

All UniProt accessions (4): C9J8P9, P09496, F8WF69, S4R3F6

UniProt curated annotations — full annotation on UniProt →

Function. Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. 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.

Subunit / interactions. Clathrin coats are formed from molecules containing 3 heavy chains and 3 light chains. Interacts with CALY; the interaction stimulates clathrin self-assembly and clathrin-mediated endocytosis. Interacts with CKAP5 and TACC3 forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; the complex implicates clathrin triskelions.

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

Similarity. Belongs to the clathrin light chain family.

Isoforms (5)

UniProt ID	Names	Canonical?
P09496-1	Brain	yes
P09496-2	Non-brain
P09496-3	3
P09496-4	4
P09496-5	5

RefSeq proteins (10): NP_001070145, NP_001171689, NP_001171690, NP_001171691, NP_001298132, NP_001298133, NP_001298134, NP_001298135, NP_001824, NP_009027 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000996	Clathrin_L-chain	Family

Pfam: PF01086

UniProt features (17 total): modified residue 5, splice variant 4, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1, helix 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6E5N	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09496-F1	72.20	0.25

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): 105, 206, 223, 236, 242

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-168275	Entry of Influenza Virion into Host Cell via Endocytosis
R-HSA-177504	Retrograde neurotrophin signalling
R-HSA-190873	Gap junction degradation
R-HSA-196025	Formation of annular gap junctions
R-HSA-2132295	MHC class II antigen presentation
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-432720	Lysosome Vesicle Biogenesis
R-HSA-437239	Recycling pathway of L1
R-HSA-5099900	WNT5A-dependent internalization of FZD4
R-HSA-5140745	WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8866427	VLDLR internalisation and degradation
R-HSA-8964038	LDL clearance
R-HSA-432722	Golgi Associated Vesicle Biogenesis

MSigDB gene sets: 286 (showing top): REACTOME_RETROGRADE_NEUROTROPHIN_SIGNALLING, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_HDAC1, HSIAO_HOUSEKEEPING_GENES, KEGG_LYSOSOME, LANG_MYB_FAMILY_TARGETS, GOBP_CLATHRIN_COAT_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_SYNAPTIC_VESICLE_RECYCLING

GO Biological Process (7): intracellular protein transport (GO:0006886), clathrin coat assembly (GO:0048268), synaptic vesicle endocytosis (GO:0048488), cell division (GO:0051301), clathrin-dependent endocytosis (GO:0072583), endocytosis (GO:0006897), vesicle-mediated transport (GO:0016192)

GO Molecular Function (6): structural molecule activity (GO:0005198), clathrin heavy chain binding (GO:0032050), peptide binding (GO:0042277), protein-containing complex binding (GO:0044877), GTPase binding (GO:0051020), protein binding (GO:0005515)

GO Cellular Component (24): lysosome (GO:0005764), endosome (GO:0005768), Golgi apparatus (GO:0005794), spindle (GO:0005819), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), clathrin coat (GO:0030118), clathrin vesicle coat (GO:0030125), clathrin coat of trans-Golgi network vesicle (GO:0030130), clathrin coat of coated pit (GO:0030132), synaptic vesicle membrane (GO:0030672), cytoplasmic vesicle (GO:0031410), trans-Golgi network membrane (GO:0032588), endolysosome membrane (GO:0036020), clathrin-coated endocytic vesicle (GO:0045334), clathrin complex (GO:0071439), presynaptic endocytic zone membrane (GO:0098835), postsynaptic endocytic zone (GO:0098843), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), clathrin-coated pit (GO:0005905), clathrin-coated vesicle (GO:0030136), cytoplasmic vesicle membrane (GO:0030659)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	2
PCP/CE pathway	2
Plasma lipoprotein clearance	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

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
clathrin coat	4
binding	3
cytoplasm	3
cellular process	2
endomembrane system	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
protein-containing complex assembly	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
receptor-mediated endocytosis	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
transport	1
molecular_function	1
clathrin binding	1
enzyme binding	1
lytic vacuole	1
cytoplasmic vesicle	1
intracellular membrane-bounded organelle	1
microtubule cytoskeleton	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
membrane coat	1
vesicle coat	1
clathrin-coated vesicle membrane	1
Golgi apparatus	1
trans-Golgi network transport vesicle membrane	1
clathrin vesicle coat	1
clathrin-coated pit	1
plasma membrane protein complex	1
synaptic vesicle	1
exocytic vesicle membrane	1
intracellular vesicle	1
trans-Golgi network	1

Protein interactions and networks

STRING

1913 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLTA	CLTC	Q00610	959
CLTA	CLTCL1	P53675	935
CLTA	CD80	P33681	860
CLTA	CD86	P42081	815
CLTA	AP2A1	O95782	788
CLTA	ITSN2	Q9NZM3	747
CLTA	EPN2	O95208	723
CLTA	CD274	Q9NZQ7	699
CLTA	EPN3	Q9H201	680
CLTA	YWHAB	P31946	650
CLTA	PPP1CA	P08129	638
CLTA	AMPH	P49418	625
CLTA	CLINT1	Q14677	623
CLTA	CTLA4	P16410	621
CLTA	CLTB	P09497	609

IntAct

93 interactions, top by confidence:

A	B	Type	Score
TOLLIP	TOM1	psi-mi:“MI:0914”(association)	0.890
HSPA8	BAG2	psi-mi:“MI:2364”(proximity)	0.860
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
STAMBP	PIK3C2A	psi-mi:“MI:0914”(association)	0.730
CLTC	CLTA	psi-mi:“MI:0915”(physical association)	0.670
CLTA	CALY	psi-mi:“MI:0915”(physical association)	0.610
CLTA	CALY	psi-mi:“MI:0407”(direct interaction)	0.610
CLTA	CALY	psi-mi:“MI:0403”(colocalization)	0.610
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
CLTB	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
CLTA	CLTCL1	psi-mi:“MI:0914”(association)	0.530
TACC3	CLTA	psi-mi:“MI:0915”(physical association)	0.500
ADRA1A	CLTA	psi-mi:“MI:0915”(physical association)	0.460
ADRA1A	CLTA	psi-mi:“MI:0403”(colocalization)	0.460
E2	CLTA	psi-mi:“MI:0403”(colocalization)	0.440
CLTA	E2	psi-mi:“MI:0915”(physical association)	0.440
CKAP5	CLTA	psi-mi:“MI:0403”(colocalization)	0.430
CLTA	CKAP5	psi-mi:“MI:0914”(association)	0.430
CALY	AP3D1	psi-mi:“MI:0915”(physical association)	0.400
FLACC1	CLTA	psi-mi:“MI:0915”(physical association)	0.400
ULK3	CLTA	psi-mi:“MI:0915”(physical association)	0.400
POLR1A	CLTA	psi-mi:“MI:0915”(physical association)	0.400
CLTA	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
RGS2	CLTA	psi-mi:“MI:0915”(physical association)	0.370
CLTA	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.370
DUX4	CBX3	psi-mi:“MI:0914”(association)	0.350
CFTR		psi-mi:“MI:0914”(association)	0.350

BioGRID (486): CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Co-fractionation), CLTA (Co-fractionation), CLTC (Co-fractionation), CLTCL1 (Co-fractionation), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTA (Affinity Capture-MS)

ESM2 similar proteins: A0JPM9, A2AQ19, O43395, O75391, O75822, P04973, P09496, P29084, P29540, Q02614, Q0VCU8, Q13123, Q15650, Q2HJ41, Q2KIA6, Q2KJF9, Q3MHJ0, Q3UGC7, Q5BK07, Q5I0B5, Q5NVI3, Q5R5F1, Q5R8D1, Q5RAD5, Q5RE03, Q5ZJ85, Q5ZJ97, Q5ZK25, Q5ZKA4, Q66HG8, Q66JS6, Q6GMH0, Q6INR1, Q6P320, Q7SXU0, Q7SYJ9, Q7TNE3, Q8BM39, Q91WE2, Q922U1

Diamond homologs: O08585, P04973, P04975, P08081, P08082, P09496, P09497, Q6IRU5, Q9VWA1, Q8MN58

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CLTA	“form complex”	“AP-2/clathrin vescicle”	binding
CLTA	“form complex”	“AP-3/clathrin vescicle”	binding
CLTA	“form complex”	“AP-1/clathrin vescicle”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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
WNT5A-dependent internalization of FZD4	5	55.2×	3e-06
Cargo recognition for clathrin-mediated endocytosis	11	16.7×	1e-08
Clathrin-mediated endocytosis	13	16.1×	5e-10
Golgi Associated Vesicle Biogenesis	5	14.5×	2e-03
Hedgehog ‘on’ state	6	13.8×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
clathrin-dependent endocytosis	5	34.6×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1210153	GRCh37/hg19 9p13.3-13.1(chr9:36088563-39092820)x1	Pathogenic

SpliceAI

2775 predictions. Top by Δscore:

Variant	Effect	Δscore
9:36198978:GGAAA:G	acceptor_gain	1.0000
9:36199093:CTTGG:C	donor_loss	1.0000
9:36199094:TTGG:T	donor_loss	1.0000
9:36199095:TGG:T	donor_loss	1.0000
9:36199096:GGT:G	donor_loss	1.0000
9:36199097:G:T	donor_loss	1.0000
9:36199098:T:A	donor_loss	1.0000
9:36204064:A:AG	acceptor_gain	1.0000
9:36204065:A:G	acceptor_gain	1.0000
9:36204178:AGG:A	donor_loss	1.0000
9:36204179:GG:G	donor_loss	1.0000
9:36204180:G:C	donor_loss	1.0000
9:36204181:T:A	donor_loss	1.0000
9:36217597:CCAG:C	acceptor_gain	1.0000
9:36217598:CAG:C	acceptor_gain	1.0000
9:36217598:CAGC:C	acceptor_gain	1.0000
9:36217600:GCT:G	acceptor_loss	1.0000
9:36217601:C:CC	acceptor_gain	1.0000
9:36217601:CTATA:C	acceptor_loss	1.0000
9:36218298:CT:C	acceptor_gain	1.0000
9:36218300:C:CC	acceptor_gain	1.0000
9:36218305:C:CT	acceptor_gain	1.0000
9:36218309:G:GC	acceptor_gain	1.0000
9:36223372:CCTA:C	donor_gain	1.0000
9:36223375:A:AC	donor_gain	1.0000
9:36223376:C:CC	donor_gain	1.0000
9:36223376:CT:C	donor_gain	1.0000
9:36223378:C:CA	donor_gain	1.0000
9:36223501:CC:C	acceptor_gain	1.0000
9:36223502:CC:C	acceptor_gain	1.0000

AlphaMissense

1426 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:36191159:T:C	F35L	1.000
9:36191160:T:C	F35S	1.000
9:36191160:T:G	F35C	1.000
9:36191161:C:A	F35L	1.000
9:36191161:C:G	F35L	1.000
9:36191163:T:C	L36S	1.000
9:36199060:T:A	W113R	1.000
9:36199060:T:C	W113R	1.000
9:36199062:G:C	W113C	1.000
9:36199062:G:T	W113C	1.000
9:36204122:T:C	L143P	1.000
9:36204130:T:A	W146R	1.000
9:36204130:T:C	W146R	1.000
9:36211658:T:A	W211R	1.000
9:36211658:T:C	W211R	1.000
9:36211659:G:C	W211S	1.000
9:36211660:G:C	W211C	1.000
9:36211660:G:T	W211C	1.000
9:36211677:T:C	L217P	1.000
9:36211679:T:C	C218R	1.000
9:36211680:G:A	C218Y	1.000
9:36211681:T:G	C218W	1.000
9:36211715:G:C	D230H	1.000
9:36211724:C:A	R233S	1.000
9:36211725:G:C	R233P	1.000
9:36211730:C:A	R235S	1.000
9:36211733:T:C	S236P	1.000
9:36211737:T:A	V237D	1.000
9:36211740:T:A	L238H	1.000
9:36211740:T:C	L238P	1.000

dbSNP variants (sampled 300 via entrez): RS1000031030 (9:36208424 G>A,T), RS1000058249 (9:36207910 A>T), RS1000084519 (9:36201165 G>A,C), RS1000087794 (9:36209752 G>A), RS1000188470 (9:36191463 T>C), RS1000198063 (9:36191664 A>G), RS1000289189 (9:36201456 G>A), RS1000560907 (9:36209987 C>A,G), RS1000660256 (9:36197183 C>T), RS1000817690 (9:36191319 T>C), RS1000888494 (9:36190205 C>T), RS1000917050 (9:36202378 G>T), RS1001186388 (9:36191517 G>A), RS1001189107 (9:36190236 T>C), RS1001241343 (9:36190575 T>A)

Disease associations

OMIM: gene MIM:118960 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002815_5	Bipolar disorder (inflammation and infection response interaction)	6.000000e-06
GCST008097_31	Bisphosphonate-associated atypical femoral fracture	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007050	HSV1 seropositivity
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295706 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.18	Kd	65.92	nM	CHEMBL5653589
7.18	ED50	65.92	nM	CHEMBL5653589
6.26	Kd	550.3	nM	CHEMBL3752910
6.26	ED50	550.3	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148090: Binding affinity to human CLTA incubated for 45 mins by Kinobead based pull down assay	kd	0.0659	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148090: Binding affinity to human CLTA incubated for 45 mins by Kinobead based pull down assay	kd	0.5503	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression	3
Valproic Acid	affects expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
Lead	affects splicing, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
Resveratrol	affects secretion	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Copper	affects binding, decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Disulfiram	affects binding, decreases expression	1
Ivermectin	decreases expression	1
Phenylmercuric Acetate	increases expression	1
Smoke	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118956	Binding	Binding affinity to CLTA in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2UH	Abcam HEK293T CLTA KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	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,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice