CLINT1

Summary

CLINT1 (clathrin interactor 1, HGNC:23186) is a protein-coding gene on chromosome 5q33.3, encoding Clathrin interactor 1 (Q14677). Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).

This gene encodes a protein with similarity to the epsin family of endocytic adapter proteins. The encoded protein interacts with clathrin, the adapter protein AP-1 and phosphoinositides. This protein may be involved in the formation of clathrin coated vesicles and trafficking between the trans-Golgi network and endosomes. Mutations in this gene are associated with a susceptibility to schizophrenia and psychotic disorders. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 9685 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 101 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 14 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.42 (moderately constrained)
• MANE Select transcript: NM_014666
• Notable: 101 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23186
Approved symbol	CLINT1
Name	clathrin interactor 1
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Aliases	ENTH, KIAA0171, EPNR, CLINT
Ensembl gene	ENSG00000113282
Ensembl biotype	protein_coding
OMIM	607265
Entrez	9685

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 38 protein_coding, 16 nonsense_mediated_decay, 3 retained_intron

MANE Select: ENST00000411809

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

ENST00000411809, ENST00000518855, ENST00000521047, ENST00000521615, ENST00000522381, ENST00000523094, ENST00000523908, ENST00000524306, ENST00000530302, ENST00000530742, ENST00000904376, ENST00000904377, ENST00000904378, ENST00000904379, ENST00000904380, ENST00000904381, ENST00000904382, ENST00000904383, ENST00000904384, ENST00000904385, ENST00000930851, ENST00000930852, ENST00000930853, ENST00000930854, ENST00000930855, ENST00000930856, ENST00000930857, ENST00000930858, ENST00000930859, ENST00000930860, ENST00000930861, ENST00000930862, ENST00000960219, ENST00000960220, ENST00000960221, ENST00000987985, ENST00000987986, ENST00000987987, ENST00001031207, ENST00001031208, ENST00001031209, ENST00001031210, ENST00001031211, ENST00001031212, ENST00001031213, ENST00001031214, ENST00001031215, ENST00001031216, ENST00001031217, ENST00001079372, ENST00001079373, ENST00001079374, ENST00001079375, ENST00001079376, ENST00001114772, ENST00001114773, ENST00001135904

RefSeq mRNA: 3 — MANE Select: NM_014666 NM_001195555, NM_001195556, NM_014666

CCDS: CCDS47330, CCDS56388, CCDS56389

Canonical transcript exons

ENST00000411809 — 12 exons

Exon	Start	End
ENSE00000768573	157816734	157816830
ENSE00001084563	157814185	157814293
ENSE00001084564	157785747	157787992
ENSE00001120766	157805866	157806112
ENSE00001120773	157809628	157809805
ENSE00001120777	157813063	157813227
ENSE00002101605	157858930	157859145
ENSE00003467363	157791703	157791995
ENSE00003485758	157803650	157803719
ENSE00003534725	157817443	157817547
ENSE00003538550	157789363	157789513
ENSE00003619311	157794898	157794972

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 70.5455 / max 1784.9772, expressed in 1826 samples.

Highest expression (Bgee): palpebral conjunctiva, esophagus squamous epithelium, corpus epididymis, bronchial epithelial cell, epithelium of nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLINT1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.0e-19	+0.16	5:157894180:T:A
Cells Cultured fibroblasts	sqtl	2.5e-19	-0.96	5:157784597:G:T
Lung	eqtl	1.6e-13	-0.17	5:157918941:T:A
Esophagus Mucosa	sqtl	6.8e-13	-0.80	5:157788705:C:T
Testis	eqtl	2.3e-11	+0.11	5:157956514:C:T
Cells Cultured fibroblasts	eqtl	4.9e-10	+0.13	5:157797361:A:G
Skin Sun Exposed Lower leg	eqtl	1.2e-05	+0.12	5:157819207:C:G
Colon Transverse	eqtl	1.7e-05	+0.10	5:157826638:G:T
Cells EBV-transformed lymphocytes	sqtl	1.8e-05	-0.87	5:157784597:G:T
Lung	sqtl	7.5e-05	-0.53	5:157784597:G:T
Adipose Visceral Omentum	sqtl	8.6e-05	-0.65	5:157842409:C:A
Colon Transverse	sqtl	1.3e-04	-0.69	5:157787426:T:C
Artery Tibial	sqtl	2.7e-04	-0.53	5:157784597:G:T
Adipose Subcutaneous	sqtl	3.1e-04	-0.52	5:157787426:T:C
Muscle Skeletal	eqtl	4.7e-04	+0.25	5:157833248:A:C
Nerve Tibial	eqtl	1.1e-03	-0.11	5:157960363:C:T
Esophagus Muscularis	sqtl	2.4e-03	-0.55	5:157871925:T:C
Pancreas	sqtl	3.6e-03	-0.66	5:157849362:G:A
Artery Tibial	eqtl	5.4e-03	+0.10	5:157782294:C:T
Thyroid	eqtl	5.8e-03	+0.12	5:157788705:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
64547	68.9075	1826
64546	1.6379	938

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	98.93	gold quality
esophagus squamous epithelium	UBERON:0006920	98.18	gold quality
corpus epididymis	UBERON:0004359	98.14	gold quality
bronchial epithelial cell	CL:0002328	98.08	gold quality
epithelium of nasopharynx	UBERON:0001951	98.08	gold quality
gingival epithelium	UBERON:0001949	97.96	gold quality
choroid plexus epithelium	UBERON:0003911	97.91	gold quality
gall bladder	UBERON:0002110	97.75	gold quality
epithelium of bronchus	UBERON:0002031	97.73	gold quality
bronchus	UBERON:0002185	97.70	gold quality
caput epididymis	UBERON:0004358	97.64	gold quality
gingiva	UBERON:0001828	97.50	gold quality
penis	UBERON:0000989	97.49	gold quality
tibia	UBERON:0000979	97.48	gold quality
rectum	UBERON:0001052	97.48	gold quality
pylorus	UBERON:0001166	97.46	gold quality
tonsil	UBERON:0002372	97.39	gold quality
esophagus mucosa	UBERON:0002469	97.37	gold quality
pharyngeal mucosa	UBERON:0000355	97.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.33	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.32	gold quality
oral cavity	UBERON:0000167	97.26	gold quality
cauda epididymis	UBERON:0004360	97.22	gold quality
minor salivary gland	UBERON:0001830	97.20	gold quality
bone marrow cell	CL:0002092	97.12	gold quality
mouth mucosa	UBERON:0003729	97.09	gold quality
nephron tubule	UBERON:0001231	97.05	gold quality
bone marrow	UBERON:0002371	97.00	gold quality
colonic mucosa	UBERON:0000317	96.95	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.93	gold quality
epithelium of esophagus	UBERON:0001976	96.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.81	gold quality
biceps brachii	UBERON:0001507	96.78	gold quality
colonic epithelium	UBERON:0000397	96.77	gold quality
superior surface of tongue	UBERON:0007371	96.73	gold quality
germinal epithelium of ovary	UBERON:0001304	96.60	gold quality
secondary oocyte	CL:0000655	96.59	gold quality
renal medulla	UBERON:0000362	96.57	gold quality
upper leg skin	UBERON:0004262	96.49	gold quality
mammalian vulva	UBERON:0000997	96.48	gold quality
islet of Langerhans	UBERON:0000006	96.44	gold quality
amniotic fluid	UBERON:0000173	96.44	gold quality
body of pancreas	UBERON:0001150	96.39	gold quality
jejunum	UBERON:0002115	96.37	gold quality
skin of abdomen	UBERON:0001416	96.32	gold quality
duodenum	UBERON:0002114	96.27	gold quality
vagina	UBERON:0000996	96.25	gold quality
metanephros cortex	UBERON:0010533	96.23	gold quality
seminal vesicle	UBERON:0000998	96.21	gold quality
squamous epithelium	UBERON:0006914	96.19	gold quality
jejunal mucosa	UBERON:0000399	96.16	gold quality
skin of leg	UBERON:0001511	96.13	gold quality
zone of skin	UBERON:0000014	96.11	gold quality
trabecular bone tissue	UBERON:0002483	96.04	gold quality
saliva-secreting gland	UBERON:0001044	95.99	gold quality
transverse colon	UBERON:0001157	95.97	gold quality
buccal mucosa cell	CL:0002336	95.96	gold quality
urethra	UBERON:0000057	95.95	gold quality
caecum	UBERON:0001153	95.94	gold quality
vermiform appendix	UBERON:0001154	95.94	gold quality
monocyte	CL:0000576	95.90	gold quality
mononuclear cell	CL:0000842	95.88	gold quality
skin of hip	UBERON:0001554	95.80	gold quality
urinary bladder	UBERON:0001255	95.79	gold quality
tongue	UBERON:0001723	95.78	gold quality
pancreas	UBERON:0001264	95.76	gold quality
large intestine	UBERON:0000059	95.73	gold quality
intestine	UBERON:0000160	95.70	gold quality
leukocyte	CL:0000738	95.67	gold quality
colon	UBERON:0001155	95.67	gold quality
smooth muscle tissue	UBERON:0001135	95.63	gold quality
cardia of stomach	UBERON:0001162	95.57	gold quality
esophagus	UBERON:0001043	95.53	gold quality
small intestine	UBERON:0002108	95.53	gold quality
body of stomach	UBERON:0001161	95.52	gold quality
adrenal tissue	UBERON:0018303	95.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.48	gold quality
stomach	UBERON:0000945	95.47	gold quality
oocyte	CL:0000023	95.46	gold quality
stromal cell of endometrium	CL:0002255	95.46	gold quality
right lobe of liver	UBERON:0001114	95.43	gold quality
lower esophagus mucosa	UBERON:0035834	95.33	gold quality
endometrium	UBERON:0001295	95.31	gold quality
heart right ventricle	UBERON:0002080	95.30	gold quality
liver	UBERON:0002107	95.30	gold quality
nasal cavity mucosa	UBERON:0001826	95.29	gold quality
lymph node	UBERON:0000029	95.28	gold quality
sigmoid colon	UBERON:0001159	95.24	gold quality
tongue squamous epithelium	UBERON:0006919	95.22	gold quality
cartilage tissue	UBERON:0002418	95.11	gold quality
body of tongue	UBERON:0011876	95.11	gold quality
cortex of kidney	UBERON:0001225	95.09	gold quality
trachea	UBERON:0003126	95.09	gold quality
parietal pleura	UBERON:0002400	94.99	gold quality
left lobe of thyroid gland	UBERON:0001120	94.96	gold quality
fundus of stomach	UBERON:0001160	94.95	gold quality
ectocervix	UBERON:0012249	94.92	gold quality
right lobe of thyroid gland	UBERON:0001119	94.90	gold quality
calcaneal tendon	UBERON:0003701	94.90	gold quality
synovial joint	UBERON:0002217	94.87	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	5.44
E-MTAB-6678	no	3.93
E-CURD-112	no	2.71
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Parathyroid gland	tissue	106.5	high
Bone marrow	tissue	95.5	medium
Liver	tissue	83.7	medium
Tonsil	tissue	69.2	high
Esophagus	tissue	67.7	medium
Kidney	tissue	65.7	high
Stomach 1	tissue	65.3	high
Duodenum	tissue	64.3	high
Urinary bladder	tissue	60.3	high
Gallbladder	tissue	57.6	high
Thyroid gland	tissue	52.4	medium
Small intestine	tissue	52.4	high
Spinal cord	tissue	52.0
Epididymis	tissue	51.2	high
Colon	tissue	50.6	high
Rectum	tissue	50.2	high
Skeletal muscle	tissue	49.8	low
Hippocampal formation	tissue	48.3
Salivary gland	tissue	47.8	high
Thymus	tissue	47.2
Prefrontal cortex	tissue	47.0
Cerebral cortex	tissue	47.0	high
Superior colliculi	tissue	46.8
Midbrain	tissue	46.7
Pancreas	tissue	46.5	medium
Lymph node	tissue	46.2	medium
Substantia nigra	tissue	45.4
Motor cortex	tissue	45.2
Medulla oblongata	tissue	45.1
Thalamus	tissue	45.0
Entorhinal cortex	tissue	45.0
Occipital cortex	tissue	45.0
Pons	tissue	44.9
Placenta	tissue	44.2	medium
Corpus callosum	tissue	43.8
Putamen	tissue	43.1
Periaqueductal gray	tissue	43.1
Septum	tissue	42.7
Somatosensory cortex	tissue	42.6
Temporal cortex	tissue	42.2
Hypothalamus	tissue	42.1
Retrosplenial and cingulate cortex	tissue	41.6
Retrosplenial cortex	tissue	40.7
Appendix	tissue	40.4	high
Seminal vesicle	tissue	39.9	high
Ventral forebrain	tissue	39.2
Tongue	tissue	38.4
Amygdala	tissue	38.1
Insular cortex	tissue	37.8
Skin 1	tissue	37.5	medium
Basal ganglia	tissue	37.0	medium
Vagina	tissue	36.7	medium
Choroid plexus	tissue	36.4
Fallopian tube	tissue	35.6	medium
Olfactory bulb	tissue	34.3
Cervix	tissue	34.2	high
Lung	tissue	34.2	medium
Adrenal gland	tissue	32.4	high
Heart muscle	tissue	32.1	medium
Caudate putamen	tissue	31.9

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (52.0), Dorsal spinal cord (50.6), Dorsal hippocampus (48.3), Subiculum (47.7), Ventral hippocampus (44.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

Targeting CLINT1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 104 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-95-5P	99.89	72.17	3973

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.419, missense Z 1.95 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000411809 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:157,787,649–157,805,910	374 / 409.6	0.91	no
5:157,805,911–157,858,970	241 / 368.6	0.65	no

Literature-anchored findings (GeneRIF, showing 13)

• a novel clathrin-associated protein identified through subcellular proteomics; data suggest a role in clathrin-mediated budding on internal membranes (PMID:12213833)
• might participate in the formation of clathrin-coated vesicles at the level of the trans-Golgi network and remains associated with the vesicles longer than clathrin and adaptors (PMID:12429846)
• EpsinR is an ENTH domain-containing protein that interacts with AP-1 (PMID:12589059)
• Our work reveals the existence of clathrin-independent and -dependent transport steps in the retrograde route, and establishes a function for clathrin and epsinR at the endosome-TGN interface. (PMID:15068792)
• epsinR is an adaptor for vesicle-associated soluble NSF attachment protein receptor (PMID:15371541)
• Four adjacent markers at the 5’ end of the Epsin 4 gene showed significant evidence of linkage disequilibrium with schizophrenia. (PMID:15793701)
• Results indicate the presence of a locus near the 5’ end of Epsin 4 conferring susceptibility to the disease and provide further support for Epsin 4 as an important potential contributor to genetic risk in schizophrenia. (PMID:16402136)
• characterization of the molecular details governing the sorting of a SNARE into clathrin-coated vesicles, namely the direct recognition of the three-helical bundle H(abc) domain of the mouse SNARE Vti1b by the human clathrin adaptor epsinR (PMID:18033301)
• Our results suggest that the examined region of Epsin 4 does not have a major influence on susceptibility to schizophrenia in Japanese. (PMID:18696005)
• Variation in the Epsin 4 gene is significantly associated with psychotic disorder in this Latino population (PMID:18929466)
• These results do not support a significant role of GRIA1 or CLINT1 in the development of schizophrenia in the German population. (PMID:21116212)
• Although epsinR has been shown to be a cargo adaptor, the present study indicates that it is an order of magnitude more abundant in CCVs than its known cargo protein, vti1b, suggesting that it may have other functions as well. (PMID:26179914)
• The cargo adapter protein CLINT1 is phosphorylated by the Numb-associated kinase BIKE and mediates dengue virus infection. (PMID:35452674)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	clint1b	ENSDARG00000089914
mus_musculus	Clint1	ENSMUSG00000006169
rattus_norvegicus	Clint1	ENSRNOG00000005406
drosophila_melanogaster	lqfR	FBGN0261279

Paralogs (5): EPN3 (ENSG00000049283), EPN1 (ENSG00000063245), EPN2 (ENSG00000072134), MYCBPAP (ENSG00000136449), ENTHD1 (ENSG00000176177)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2144243) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal placenta morphology	1
edema	1
embryonic growth retardation	1
preweaning lethality, complete penetrance	1

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	A7Z035	92.1%	Diamond
Saccharomyces cerevisiae S288C	Q05785	60.4%	Diamond
Arabidopsis thaliana	Q67YI9	60.2%	Diamond
Schizosaccharomyces pombe 972h-	P78813	57.4%	Diamond
Dictyostelium discoideum	Q54EH1	50.0%	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
LSM11	protein-coding	134353
THG1L	protein-coding	54974

Protein

Protein identifiers

Clathrin interactor 1 — Q14677 (reviewed: Q14677)

Alternative names: Clathrin-interacting protein localized in the trans-Golgi region, Enthoprotin, Epsin-4, Epsin-related protein

All UniProt accessions (6): Q14677, A0A0S2Z4Y4, A0A0S2Z5H3, H0YCL3, H0YD52, H0YDU9

UniProt curated annotations — full annotation on UniProt →

Function. Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly.

Subunit / interactions. Binds clathrin heavy chain and AP-2. Interacts with VTI1B. Interacts with GGA2 (via GAE domain). Interacts with AP1G1 (via GAE domain). Interacts with AP1G2 (via GAE domain).

Subcellular location. Cytoplasm. Perinuclear region. Membrane. Cytoplasmic vesicle. Clathrin-coated vesicle.

Tissue specificity. Ubiquitously expressed at low to intermediate levels.

Polymorphism. Genetic variations in CLINT1 may contribute to susceptibility to schizophrenia (SCZD1) and psychotic disorders in some populations.

Similarity. Belongs to the epsin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14677-1	1	yes
Q14677-2	2
Q14677-3	3

RefSeq proteins (3): NP_001182484, NP_001182485, NP_055481* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008942	ENTH_VHS	Homologous_superfamily
IPR013809	ENTH	Domain

Pfam: PF01417

UniProt features (54 total): mutagenesis site 15, modified residue 11, helix 10, region of interest 6, splice variant 3, binding site 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, strand 1, turn 1

Structure

Experimental structures (PDB)

3 structures by resolution:

PDB	Title	Method	Resolution (Å)
1XGW	The crystal structure of human enthoprotin N-terminal domain	X-RAY DIFFRACTION	1.9
2QY7	Crystal structure of human epsinR ENTH domain	X-RAY DIFFRACTION	2
2V8S	VTI1B HABC DOMAIN - EPSINR ENTH DOMAIN COMPLEX	X-RAY DIFFRACTION	2.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14677-F1	58.15	0.21

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoplasm

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

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

Ligand- & substrate-binding residues (2)

Position	Role
29	a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)
67	a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate)

Post-translational modifications (11)

Type	Positions
Phosphoserine	163, 166, 173, 205, 210, 227, 245, 299, 312, 624
Phosphothreonine	308

Mutagenesis-validated functional residues (15)

Position	Phenotype
29	reduces lipid binding. abolishes lipid binding; when associated with g-34.
34	abolishes lipid binding; when associated with l-29.
41	normal binding to vti1b.
46	normal binding to vti1b.
52	abolished binding to vti1b.
53–54	abolished binding to vti1b.
95	normal binding to vti1b.
96	abolished binding to vti1b.
146	abolished binding to vti1b. rescued binding to vti1b r-23 mutant.
153	normal binding to vti1b.
159	normal binding to vti1b.
349	decreases ap-1 and ap-2 binding.
371	slightly decreases ap-1 binding.
422	strongly decreases clathrin binding.
423–426	strongly reduces clathrin binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9918476	Assembly and Release of Dengue Virus Virions ⚕	curated
R-HSA-432722	Golgi Associated Vesicle Biogenesis	curated
R-HSA-199991	Membrane Trafficking	—
R-HSA-5653656	Vesicle-mediated transport	—
R-HSA-199992	trans-Golgi Network Vesicle Budding	—

MSigDB gene sets: 197 (showing top): IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_CLATHRIN_COAT_ASSEMBLY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, ONKEN_UVEAL_MELANOMA_UP, GOCC_COATED_VESICLE, HEN1_01, GENTILE_UV_HIGH_DOSE_DN, GOCC_VESICLE_COAT, SCHLOSSER_SERUM_RESPONSE_DN, RYTTCCTG_ETS2_B, SESTO_RESPONSE_TO_UV_C5, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, ATCATGA_MIR433, BASAKI_YBX1_TARGETS_DN

GO Biological Process (2): endocytosis (GO:0006897), clathrin coat assembly (GO:0048268)

GO Molecular Function (5): phospholipid binding (GO:0005543), clathrin binding (GO:0030276), cadherin binding (GO:0045296), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (11): endosome (GO:0005768), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), clathrin vesicle coat (GO:0030125), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737), endomembrane system (GO:0012505), clathrin-coated vesicle (GO:0030136), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

4 top-level categories:

Category	Pathways
trans-Golgi Network Vesicle Budding	1
Dengue Virus Infection	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

23 GO namespaces:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
binding	2
endomembrane system	2
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
protein-containing complex assembly	1
lipid binding	1
protein binding	1
cell adhesion molecule binding	1
cytoplasmic vesicle	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
clathrin coat	1
vesicle coat	1
clathrin-coated vesicle membrane	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1
coated vesicle	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi apparatus	CC	direct assay
membrane	CC	high-throughput assay
cadherin binding	MF	high-throughput assay
clathrin binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,588 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLINT1	VTI1B	Q9UEU0	855
CLINT1	SNAP91	O60641	793
CLINT1	PICALM	Q13492	783
CLINT1	CLTCL1	P53675	778
CLINT1	CLTC	Q00610	754
CLINT1	CLTB	P09497	689
CLINT1	CLTA	P09496	670
CLINT1	GGA2	Q9UJY4	667
CLINT1	GABRP	O00591	646
CLINT1	AP2A1	O95782	644
CLINT1	EPS15	P42566	574
CLINT1	AMPH	P49418	570
CLINT1	GABRB2	P47870	566
CLINT1	BIN1	O00499	499
CLINT1	DAOA	P59103	498

IntAct

Human interaction partners of CLINT1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

17 partners by confidence:

Partner	Interaction type	MIscore	Records
BMP2K	physical association	0.710	6
VTI1B	proximity	0.610	1
GDPD5	physical association	0.560	3
KIF1B	physical association	0.560	3
WFS1	physical association	0.560	3
PIK3C2A	association	0.530	3
GABARAPL1	direct interaction	0.520	1
MAP1LC3B	direct interaction	0.520	1
AP2B1	direct interaction	0.440	1
GABARAP	direct interaction	0.440	1
GABARAPL2	direct interaction	0.440	1
MAP1LC3C	direct interaction	0.440	1
RABEP1	physical association	0.400	1
GGA2	association	0.350	1
MAP4	association	0.350	1
DYNLL1	physical association	0.000	1
DYNLL2	physical association	0.000	1

BioGRID (333 interactions; top human partners by supporting records): AP1B1 (Affinity Capture-MS; 4 records), CLTC (Affinity Capture-MS; 4 records), GGA2 (Affinity Capture-MS; 4 records), AP1G1 (Reconstituted Complex; 3 records), AP1S2 (Affinity Capture-MS; 3 records), AP2A1 (Affinity Capture-MS; 3 records), AP2B1 (Co-fractionation; 3 records), AP2M1 (Affinity Capture-MS; 3 records), CLTB (Affinity Capture-MS; 3 records), PICALM (Affinity Capture-MS; 3 records), SMAP2 (Affinity Capture-MS; 3 records), STAMBP (Affinity Capture-MS; 3 records), STAMBPL1 (Affinity Capture-MS; 3 records), VTI1B (Affinity Capture-MS; 3 records), ANLN (Affinity Capture-MS; 2 records)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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
TBC/RABGAPs	5	86.5×	1e-07
Macroautophagy	7	53.8×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	5	103.3×	6e-08
mitophagy	5	93.5×	6e-08
autophagosome assembly	5	66.1×	3e-07

Disease & clinical

Genetic variants

Variant evidence for CLINT1: 101 ClinVar records (0 pathogenic / likely pathogenic); 7 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 1,160):

Position(s)	Effect	Δscore	Sites
5:157794896–157794897	donor_loss	1.0000	5
5:157805870	donor_gain	1.0000
5:157806113–157806114	acceptor_loss	1.0000	5
5:157806120–157806123	acceptor_gain	1.0000	3
5:157809626–157809627	donor_loss	1.0000	5
5:157809806–157809807	acceptor_loss	1.0000	3
5:157813230	acceptor_gain	1.0000
5:157813236	acceptor_gain	1.0000
5:157814183–157814184	donor_loss	1.0000	5
5:157814294–157814295	acceptor_loss	1.0000	5

AlphaMissense

1,653 missense substitutions predicted likely pathogenic (of 4,168 scored), across 359 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
M63	9	0.981	0.998
M44	9	0.951	0.999
M68	9	0.932	0.999
M19	9	0.923	1.000
M61	9	0.886	0.997
D123	8	0.998	1.000
H104	8	0.996	1.000
N20	8	0.994	0.999
D118	8	0.990	0.999
D107	8	0.989	0.998
D12	8	0.986	0.999
D142	8	0.985	0.999
D34	8	0.982	1.000
N127	8	0.973	1.000
F57	8	0.966	0.999
D141	8	0.964	0.996
D157	8	0.964	0.996
N16	8	0.957	0.999
F617	8	0.956	0.994
D35	8	0.949	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.76e-09
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000126
Colon Adenocarcinoma (TCGA)	favorable	0.00038
Rectum Adenocarcinoma (validation)	unfavorable	0.000422

Disease associations

OMIM: gene MIM:607265 | disease phenotypes:

GWAS associations

7 associations:

Study	Trait	p-value
GCST007099_85	Systolic blood pressure	1e-19
GCST007094_15	Diastolic blood pressure	3e-19
GCST007095_122	Systolic blood pressure	6e-8
GCST007098_73	Diastolic blood pressure	7e-8
GCST007096_1	Pulse pressure	1e-7
GCST007095_123	Systolic blood pressure	2e-7
GCST007098_74	Diastolic blood pressure	2e-7

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066453 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.78	Kd	164.3	nM	CHEMBL5653589
6.78	ED50	164.3	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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	2148082: Binding affinity to human CLINT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1643	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	affects phosphorylation	1
Copper	increases expression, affects binding	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Formaldehyde	decreases expression	1
Furaldehyde	affects localization, increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Ozone	affects expression, increases abundance	1
Sodium Chloride	affects cotreatment, affects localization, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Uranium	affects expression	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651124	Binding	Binding affinity to human CLINT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CLINT1 across ~30M SureChEMBL compounds — explore on Sugi Predict.