CLVS1

Summary

CLVS1 (clavesin 1, HGNC:23139) is a protein-coding gene on chromosome 8q12.2-q12.3, encoding Clavesin-1 (Q8IUQ0). Required for normal morphology of late endosomes and/or lysosomes in neurons.

Enables phosphatidylinositol-3,5-bisphosphate binding activity. Predicted to be involved in lysosome organization. Located in endosome.

Source: NCBI Gene 157807 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_173519

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23139
Approved symbol	CLVS1
Name	clavesin 1
Location	8q12.2-q12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC34646, CRALBPL, C6orf212L
Ensembl gene	ENSG00000177182
Ensembl biotype	protein_coding
OMIM	611292
Entrez	157807

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000325897, ENST00000518426, ENST00000518592, ENST00000518858, ENST00000519846, ENST00000520712, ENST00000521189, ENST00000522621, ENST00000522928, ENST00000523868, ENST00000524095, ENST00000851313, ENST00000912366

RefSeq mRNA: 1 — MANE Select: NM_173519 NM_173519

CCDS: CCDS6176

Canonical transcript exons

ENST00000325897 — 6 exons

Exon	Start	End
ENSE00001087276	61299677	61300282
ENSE00003516133	61376605	61376779
ENSE00003558306	61458307	61458542
ENSE00003666568	61454141	61454251
ENSE00003843108	61499455	61501629
ENSE00003849454	61287970	61288138

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 92.17.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1586 / max 276.5256, expressed in 229 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89063	2.3069	147
89054	0.7958	121
89064	0.0475	34
89053	0.0084	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.17	gold quality
ganglionic eminence	UBERON:0004023	91.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.84	gold quality
ventricular zone	UBERON:0003053	84.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.66	gold quality
prefrontal cortex	UBERON:0000451	79.34	gold quality
cerebellar cortex	UBERON:0002129	78.92	gold quality
cerebellar hemisphere	UBERON:0002245	78.92	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.66	gold quality
cerebellum	UBERON:0002037	77.35	gold quality
anterior cingulate cortex	UBERON:0009835	76.29	gold quality
nucleus accumbens	UBERON:0001882	76.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.53	gold quality
caudate nucleus	UBERON:0001873	74.85	gold quality
neocortex	UBERON:0001950	74.81	gold quality
putamen	UBERON:0001874	74.64	gold quality
right frontal lobe	UBERON:0002810	74.58	gold quality
hypothalamus	UBERON:0001898	74.53	gold quality
frontal cortex	UBERON:0001870	74.29	gold quality
cerebral cortex	UBERON:0000956	72.53	gold quality
brain	UBERON:0000955	71.61	gold quality
amygdala	UBERON:0001876	71.55	gold quality
forebrain	UBERON:0001890	71.49	gold quality
buccal mucosa cell	CL:0002336	69.29	gold quality
Ammon’s horn	UBERON:0001954	67.65	gold quality
primary visual cortex	UBERON:0002436	66.84	gold quality
substantia nigra	UBERON:0002038	66.14	gold quality
temporal lobe	UBERON:0001871	65.57	gold quality
adenohypophysis	UBERON:0002196	64.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting CLVS1, 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-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 3)

• CRALBPL may be used as a marker for human hepatocellular carcinomas. (PMID:18271718)
• Clavesin protein family appears to provide a unique neuron-specific regulation of late endosome/lysosome morphology. (PMID:19651769)
• Steroid-sensitive nephrotic syndrome candidate gene CLVS1 regulates podocyte oxidative stress and endocytosis. (PMID:34874915)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
mus_musculus	Clvs1	ENSMUSG00000041216
rattus_norvegicus	Clvs1	ENSRNOG00000006919
drosophila_melanogaster	CG3191	FBGN0023525
drosophila_melanogaster	CG3091	FBGN0029608
drosophila_melanogaster	CG3823	FBGN0029863
drosophila_melanogaster	CG1902	FBGN0033434
drosophila_melanogaster	CG12926	FBGN0033437
drosophila_melanogaster	CG10301	FBGN0039106
drosophila_melanogaster	CG10300	FBGN0039107
drosophila_melanogaster	CG30339	FBGN0050339
drosophila_melanogaster	CG31636	FBGN0051636
drosophila_melanogaster	CG33514	FBGN0053514
drosophila_melanogaster	CG33965	FBGN0053965
drosophila_melanogaster	CG33966	FBGN0053966

Paralogs (3): TTPAL (ENSG00000124120), RLBP1 (ENSG00000140522), CLVS2 (ENSG00000146352)

Protein

Protein identifiers

Clavesin-1 — Q8IUQ0 (reviewed: Q8IUQ0)

Alternative names: Cellular retinaldehyde-binding protein-like, Retinaldehyde-binding protein 1-like 1, clathrin vesicle-associated Sec14 protein 1

All UniProt accessions (5): A0A1D5RMS6, E5RI68, E5RK22, G3V122, Q8IUQ0

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal morphology of late endosomes and/or lysosomes in neurons. Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).

Subunit / interactions. Forms a complex with clathrin heavy chain and gamma-adaptin.

Subcellular location. Golgi apparatus. trans-Golgi network membrane. Cytoplasmic vesicle. Clathrin-coated vesicle. Early endosome membrane.

Tissue specificity. Expressed mainly in the brain.

Domain organisation. The CRAL-TRIO domain is required for targeting to the membrane and for binding PtdIns(3,5)P2.

Miscellaneous. Binding to PtdIns(3,5)P2 is not required for localization. May be due to an intron retention.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IUQ0-1	1	yes
Q8IUQ0-2	2

RefSeq proteins (1): NP_775790* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001251	CRAL-TRIO_dom	Domain
IPR011074	CRAL/TRIO_N_dom	Domain
IPR036273	CRAL/TRIO_N_dom_sf	Homologous_superfamily
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily

Pfam: PF00650, PF03765

UniProt features (9 total): compositionally biased region 2, splice variant 2, chain 1, domain 1, region of interest 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUQ0-F1	82.01	0.74

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
83–85	abolishes binding to ptdins(3,5)p2. no effect on subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-432720	Lysosome Vesicle Biogenesis

MSigDB gene sets: 171 (showing top): GOBP_VACUOLE_ORGANIZATION, GCANCTGNY_MYOD_Q6, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, TAL1ALPHAE47_01, REACTOME_MEMBRANE_TRAFFICKING, CACCAGC_MIR138, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, GOCC_TRANS_GOLGI_NETWORK, GATA3_01, YY1_02, OCT1_03

GO Biological Process (1): lysosome organization (GO:0007040)

GO Molecular Function (4): phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), phosphatidylinositol bisphosphate binding (GO:1902936), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (8): endosome (GO:0005768), trans-Golgi network (GO:0005802), clathrin-coated vesicle (GO:0030136), early endosome membrane (GO:0031901), trans-Golgi network membrane (GO:0032588), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
endomembrane system	2
cytoplasm	2
lytic vacuole organization	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
anion binding	1
cytoplasmic vesicle	1
Golgi apparatus subcompartment	1
coated vesicle	1
early endosome	1
endosome membrane	1
trans-Golgi network	1
organelle membrane	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLVS1	N4BP2L1	Q5TBK1	545
CLVS1	TMEM92	Q6UXU6	522
CLVS1	ZNF618	Q5T7W0	512
CLVS1	IGSF21	Q96ID5	491
CLVS1	PALMD	Q9NP74	476
CLVS1	LRMDA	Q9H2I8	476
CLVS1	KCNH7	Q9NS40	462
CLVS1	TRIM28	Q13263	437
CLVS1	NPAS3	Q8IXF0	437
CLVS1	VPS13C	Q709C8	427
CLVS1	ADGRL2	O95490	426
CLVS1	SEMA5A	Q13591	410
CLVS1	GCSAML	Q5JQS6	396
CLVS1	PI3	P19957	395
CLVS1	ZNF589	Q86UQ0	394
CLVS1	MTMR8	Q96EF0	394

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CLVS1	AHSP	psi-mi:“MI:0915”(physical association)	0.560
LRRK1	CLVS1	psi-mi:“MI:0407”(direct interaction)	0.440
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
CLVS1	AHSP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): CLVS1 (Reconstituted Complex), CLVS1 (Two-hybrid), CLVS1 (Reconstituted Complex)

ESM2 similar proteins: A0A3L7I2I8, A6JFQ6, A6JUQ6, A7MBL8, E1C3P4, O08874, O60733, O70291, O94806, P41034, P49638, P97570, P97819, Q02384, Q07889, Q07890, Q16513, Q2KIX2, Q3LAC4, Q4R678, Q5E9G6, Q5F361, Q5M7E1, Q5RCA6, Q5SPP0, Q5SYC1, Q641K1, Q66H63, Q6NRC7, Q70Z35, Q8BG92, Q8BM85, Q8BWP5, Q8BWW9, Q8CA95, Q8IUQ0, Q8K1Y2, Q8NHP6, Q8TEA7, Q8W4D4

Diamond homologs: A6JFQ6, A6JUQ6, E1C1U1, P10123, P12271, P41034, P49638, Q19895, Q5M7E1, Q5RCA6, Q5RFR0, Q5SPP0, Q5SYC1, Q8BG92, Q8BWP5, Q8IUQ0, Q95KF7, Q9BTX7, Q9D3D0, Q9D4C9, Q9Z275, P53989, P49193, O76054, P45816, Q99J08, Q99MS0, Q8R0F9, Q9UDX3, O35239, P43378, Q641Z2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2358 predictions. Top by Δscore:

Variant	Effect	Δscore
8:61300241:G:GT	donor_gain	1.0000
8:61391090:ACT:A	acceptor_gain	1.0000
8:61391092:T:A	acceptor_gain	1.0000
8:61454133:T:TA	acceptor_gain	1.0000
8:61458304:C:G	acceptor_gain	1.0000
8:61458305:A:AG	acceptor_gain	1.0000
8:61458305:AGA:A	acceptor_loss	1.0000
8:61458306:G:GA	acceptor_gain	1.0000
8:61458306:GA:G	acceptor_gain	1.0000
8:61458306:GAT:G	acceptor_gain	1.0000
8:61458306:GATT:G	acceptor_gain	1.0000
8:61458306:GATTT:G	acceptor_gain	1.0000
8:61458542:GGTAA:G	donor_loss	1.0000
8:61458544:T:A	donor_loss	1.0000
8:61299676:G:GA	acceptor_gain	0.9900
8:61299676:GTA:G	acceptor_gain	0.9900
8:61299676:GTAA:G	acceptor_gain	0.9900
8:61300277:GA:G	donor_gain	0.9900
8:61300279:G:GG	donor_gain	0.9900
8:61322438:A:G	donor_gain	0.9900
8:61391087:A:AG	acceptor_gain	0.9900
8:61391088:ATACT:A	acceptor_gain	0.9900
8:61454133:T:A	acceptor_loss	0.9900
8:61454136:CCCA:C	acceptor_loss	0.9900
8:61454137:CCA:C	acceptor_loss	0.9900
8:61454138:CA:C	acceptor_loss	0.9900
8:61454139:A:AC	acceptor_loss	0.9900
8:61454140:GGACA:G	acceptor_gain	0.9900
8:61454250:GG:G	donor_gain	0.9900
8:61454251:GG:G	donor_gain	0.9900

AlphaMissense

2344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:61300062:T:C	F79L	1.000
8:61300064:T:A	F79L	1.000
8:61300064:T:G	F79L	1.000
8:61300269:T:A	W148R	1.000
8:61300269:T:C	W148R	1.000
8:61376705:T:A	W186R	1.000
8:61376705:T:C	W186R	1.000
8:61454178:T:A	V223D	1.000
8:61454202:C:A	A231D	1.000
8:61458383:G:A	G273E	1.000
8:61300050:T:C	F75L	0.999
8:61300052:C:A	F75L	0.999
8:61300052:C:G	F75L	0.999
8:61300069:G:C	R81P	0.999
8:61300105:T:C	L93P	0.999
8:61300108:T:C	L94P	0.999
8:61300128:C:A	R101S	0.999
8:61300129:G:C	R101P	0.999
8:61300192:T:C	L122P	0.999
8:61300200:G:T	G125W	0.999
8:61300201:G:A	G125E	0.999
8:61300207:C:A	P127H	0.999
8:61300271:G:C	W148C	0.999
8:61300271:G:T	W148C	0.999
8:61376628:G:C	R160P	0.999
8:61376685:G:A	G179D	0.999
8:61376685:G:T	G179V	0.999
8:61376729:G:C	A194P	0.999
8:61376730:C:A	A194D	0.999
8:61376754:T:C	L202P	0.999

dbSNP variants (sampled 300 via entrez): RS1000003355 (8:61367708 T>A), RS1000025489 (8:61389122 A>G), RS1000028358 (8:61247775 A>C), RS1000031768 (8:61258417 G>A), RS1000038862 (8:61452458 T>A), RS1000042977 (8:61449320 A>G), RS1000043695 (8:61228298 C>T), RS1000053367 (8:61125770 A>G), RS1000055407 (8:61485575 C>T), RS1000055773 (8:61455628 A>G), RS1000055949 (8:61241643 C>A,T), RS1000057612 (8:61045281 C>T), RS1000073616 (8:61463216 G>A), RS1000074334 (8:61202836 A>T), RS1000086099 (8:61428676 A>G)

Disease associations

OMIM: gene MIM:611292 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000891_3	Whole-brain volume	6.000000e-06
GCST002450_3	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	3.000000e-06
GCST002783_133	Body mass index	5.000000e-07
GCST002783_318	Body mass index	2.000000e-06
GCST008097_29	Bisphosphonate-associated atypical femoral fracture	1.000000e-06
GCST008161_40	Waist circumference adjusted for body mass index	3.000000e-06
GCST008867_5	Tyrosine levels	6.000000e-07
GCST010988_297	Adult body size	4.000000e-08
GCST012490_433	Femur bone mineral density x serum urate levels interaction	2.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005089	whole-brain volume
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0004340	body mass index
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0007789	BMI-adjusted waist circumference
EFO:0005058	tyrosine measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	3
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	3
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, decreases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1602	NCI-N417	Cancer cell line	Female
CVCL_A592	NCI-H60	Cancer cell line	Female

Clinical trials (associated diseases)

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