VPS13B

Summary

VPS13B (vacuolar protein sorting 13 homolog B, HGNC:2183) is a protein-coding gene on chromosome 8q22.2, encoding Intermembrane lipid transfer protein VPS13B (Q7Z7G8). Mediates the transfer of lipids between membranes at organelle contact sites.

This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 157680 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Cohen syndrome (Definitive, ClinGen)
• GWAS associations: 10
• Clinical variants (ClinVar): 6,831 total — 635 pathogenic, 430 likely-pathogenic
• Phenotypes (HPO): 99
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_152564

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2183
Approved symbol	VPS13B
Name	vacuolar protein sorting 13 homolog B
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Aliases	BLTP5B
Ensembl gene	ENSG00000132549
Ensembl biotype	protein_coding
OMIM	607817
Entrez	157680

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 9 protein_coding_CDS_not_defined, 6 retained_intron, 5 nonsense_mediated_decay, 4 protein_coding

ENST00000355155, ENST00000357162, ENST00000358544, ENST00000441350, ENST00000493587, ENST00000496144, ENST00000518569, ENST00000521037, ENST00000521559, ENST00000521932, ENST00000522802, ENST00000524330, ENST00000682145, ENST00000682153, ENST00000682234, ENST00000682358, ENST00000682806, ENST00000682853, ENST00000683334, ENST00000683486, ENST00000683619, ENST00000683869, ENST00000684269, ENST00000684308

RefSeq mRNA: 4 — MANE Select: NM_152564 NM_015243, NM_017890, NM_152564, NM_181661

CCDS: CCDS47903, CCDS6280, CCDS6281

Canonical transcript exons

ENST00000357162 — 62 exons

Exon	Start	End
ENSE00001026838	99481599	99481802
ENSE00001026840	99501687	99501858
ENSE00001088654	99102953	99103120
ENSE00001088657	99111098	99111279
ENSE00001088658	99038423	99038566
ENSE00001088659	99096312	99096432
ENSE00001088660	99115700	99115874
ENSE00001088948	99442401	99442635
ENSE00001088949	99502836	99502950
ENSE00001088950	99467414	99467634
ENSE00001285813	99431537	99431664
ENSE00001285840	99275081	99275254
ENSE00001285847	99274198	99274332
ENSE00001285857	99156549	99156743
ENSE00001285865	99147841	99148010
ENSE00001285875	99142974	99143165
ENSE00001285932	99136665	99136752
ENSE00001289311	99121177	99121445
ENSE00001311413	99507137	99507203
ENSE00001337630	99135596	99135733
ENSE00001337632	99135015	99135137
ENSE00001337634	99134632	99134727
ENSE00002116985	99013274	99013347
ENSE00002135952	99013760	99013935
ENSE00003460860	99832369	99832652
ENSE00003464966	99835539	99835738
ENSE00003468271	99817540	99817803
ENSE00003478599	99861776	99861946
ENSE00003478706	99511104	99511512
ENSE00003487159	99778682	99779031
ENSE00003492557	99699525	99699932
ENSE00003503757	99717171	99717373
ENSE00003504944	99868289	99868465
ENSE00003508271	99821294	99821482
ENSE00003528394	99875418	99877580
ENSE00003539891	99577490	99577633
ENSE00003545138	99575658	99575784
ENSE00003550681	99835197	99835324
ENSE00003552307	99784315	99784476
ENSE00003558333	99819412	99819582
ENSE00003563999	99871448	99871697
ENSE00003567950	99818713	99818888
ENSE00003578651	99720863	99721047
ENSE00003582861	99661354	99661491
ENSE00003588667	99384208	99384317
ENSE00003592100	99818451	99818534
ENSE00003592248	99556450	99556653
ENSE00003603094	99391557	99391704
ENSE00003605574	99870785	99870887
ENSE00003612069	99853451	99854256
ENSE00003626050	99823832	99823978
ENSE00003626690	99766774	99766970
ENSE00003629753	99641811	99642498
ENSE00003632393	99809375	99809530
ENSE00003642686	99848776	99848894
ENSE00003655794	99776775	99776956
ENSE00003660262	99192876	99193057
ENSE00003661009	99819921	99820122
ENSE00003674714	99859304	99859480
ENSE00003682621	99520899	99521010
ENSE00003683705	99720345	99720552
ENSE00003692258	99170039	99170163

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 96.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8243 / max 453.8560, expressed in 1786 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89949	13.7886	1735
89947	3.4375	1166
89950	1.5657	882
89946	0.7404	405
89948	0.2922	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.00	gold quality
nipple	UBERON:0002030	94.27	gold quality
bronchial epithelial cell	CL:0002328	93.79	gold quality
pylorus	UBERON:0001166	93.65	gold quality
cardia of stomach	UBERON:0001162	93.04	gold quality
buccal mucosa cell	CL:0002336	92.03	gold quality
secondary oocyte	CL:0000655	91.92	gold quality
colonic epithelium	UBERON:0000397	91.77	gold quality
mammary duct	UBERON:0001765	91.56	gold quality
synovial joint	UBERON:0002217	91.45	gold quality
endothelial cell	CL:0000115	91.19	gold quality
visceral pleura	UBERON:0002401	91.19	gold quality
superficial temporal artery	UBERON:0001614	91.13	gold quality
cauda epididymis	UBERON:0004360	91.13	gold quality
urethra	UBERON:0000057	90.76	gold quality
oocyte	CL:0000023	90.58	gold quality
skin of hip	UBERON:0001554	90.56	gold quality
caput epididymis	UBERON:0004358	90.53	gold quality
epithelium of bronchus	UBERON:0002031	90.50	gold quality
bronchus	UBERON:0002185	90.48	gold quality
epithelium of mammary gland	UBERON:0003244	90.48	gold quality
upper leg skin	UBERON:0004262	90.33	gold quality
saphenous vein	UBERON:0007318	90.32	gold quality
blood vessel layer	UBERON:0004797	90.17	gold quality
calcaneal tendon	UBERON:0003701	90.06	gold quality
bone marrow cell	CL:0002092	89.62	gold quality
superior surface of tongue	UBERON:0007371	89.55	gold quality
cerebellar vermis	UBERON:0004720	89.46	gold quality
corpus epididymis	UBERON:0004359	89.40	gold quality
tendon	UBERON:0000043	89.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

93 targeting VPS13B, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 34)

• A mutated gene on chromosome 8q22 found by haplotype analysis in patients with this syndrome. (PMID:12730828)
• COH1 mutations is associated with Cohen syndrome (PMID:15141358)
• Allelic heterogeneity in the COH1 gene explains clinical variability in Cohen syndrome (PMID:15154116)
• detected 15 COH1 alterations most of them were truncating mutations, only one being a missense change. A single base deletion leading to p.T3708fs3769, never reported before, was found in three apparently unrelated families (PMID:17990063)
• A new deletion in COH1 causing Cohen syndrome was detected in a Greek island population. (PMID:18655112)
• Mutation analysis of COH1 in twelve novel patients with Cohen syndrome from nine families, was carried out. (PMID:19006247)
• Deletions in the VPS13B (COH1) gene as a cause of Cohen syndrome (PMID:19533689)
• VPS13B gene, via affecting bone mineral density and femoral neck cross-sectional geometric parameters, is a novel osteoporosis risk gene. (PMID:19680589)
• This study confirms that COH1 copy number variations are a frequent cause of Cohen syndrome and consist of intragenic deletions as well as duplications. (PMID:20461111)
• VPS13B screening is not indicated in the absence of chorioretinal dystrophy or neutropenia in patients aged over 5 years. (PMID:20656880)
• This high frequency of causal submicroscopic chromosomal aberrations in patients with congenital ocular malformation warrants implementation of array comparative genomic hybridization in the diagnostic work-up of these patients. (PMID:21353197)
• COH1 as a Golgi-associated matrix protein required for Golgi integrity. (PMID:21865173)
• This observation emphasizes that VPS13B analysis should be performed in cases of congenital neutropenia associated with retinopathy, even in the absence of ID, therefore extending the VPS13B phenotype spectrum. (PMID:24311531)
• This report emphasizes the value of a broad-based whole exome sequencing approach in disease gene identification in the syndromic retinal dystrophies, where all disease characteristics may not be present in young patients to allow a clinical diagnosis. (PMID:25060287)
• Association of COH1 with the Golgi complex is mediated by its interaction with RAB6 and is required for neurite outgrowth. (PMID:25492866)
• Novel VPS13B deletion mutations in three large Pakistani Cohen Syndrome families suggests a Baloch variant with Autistic-Like features. (PMID:26104215)
• Here, we present an 11-month-old girl with CS caused by two multi-exonic small deletions in VSP13B in trans. (PMID:28631888)
• VPS13B mutation is asociated with Cohen syndrome. (PMID:29149870)
• This study reveled VPS13B mutation in patient with intellectual deficiency-Cohen syndrome. (PMID:29758347)
• CNV analysis using whole exome sequencing identified biallelic CNVs of VPS13B in siblings with intellectual disability. (PMID:30602132)
• Mutations in the VPS13B Gene in Iranian Patients with Different Phenotypes of Cohen Syndrome. (PMID:31444703)
• Ophthalmic features of retinitis pigmentosa in Cohen syndrome caused by pathogenic variants in the VPS13B gene. (PMID:31580008)
• study presents two novel VPS13B mutations in Cohen syndrome (CS). The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS (PMID:31752730)
• A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome. (PMID:31825161)
• Autophagy pathway upregulation in a human iPSC-derived neuronal model of Cohen syndrome with VPS13B missense mutations. (PMID:32375900)
• An intronic splice site alteration in combination with a large deletion affecting VPS13B (COH1) causes Cohen syndrome. (PMID:32505691)
• Cohen Syndrome-Associated Cataract Is Explained by VPS13B Functions in Lens Homeostasis and Is Modified by Additional Genetic Factors. (PMID:32915983)
• Functional Analysis of a Compound Heterozygous Mutation in the VPS13B Gene in a Chinese Pedigree with Cohen Syndrome. (PMID:33025479)
• A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation. (PMID:33547071)
• A Novel VPS13B Mutation Identified by Whole-Exome Sequencing in Iranian Patients with Cohen Syndrome. (PMID:34041686)
• Disease relevance of rare VPS13B missense variants for neurodevelopmental Cohen syndrome. (PMID:35690661)
• A Novel Variant in VPS13B Underlying Cohen Syndrome. (PMID:37090188)
• Exome sequencing in four families with neurodevelopmental disorders: genotype-phenotype correlation and identification of novel disease-causing variants in VPS13B and RELN. (PMID:38771357)
• Sec23IP recruits VPS13B/COH1 to ER exit site-Golgi interface for tubular ERGIC formation. (PMID:39352497)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000100043
mus_musculus	Vps13b	ENSMUSG00000037646
rattus_norvegicus	Vps13b	ENSRNOG00000066252

Protein

Protein identifiers

Intermembrane lipid transfer protein VPS13B — Q7Z7G8 (reviewed: Q7Z7G8)

Alternative names: Cohen syndrome protein 1, Vacuolar protein sorting-associated protein 13B

All UniProt accessions (6): Q7Z7G8, A0A804HJ62, A0A804HKG9, A0A804HL73, A0A8C8KE22, H0YB72

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the transfer of lipids between membranes at organelle contact sites. Binds phosphatidylinositol 3-phosphate. Functions as a tethering factor in the slow endocytic recycling pathway, to assist traffic between early and recycling endosomes. Involved in the transport of proacrosomal vesicles to the nuclear dense lamina (NDL) during spermatid development. Plays a role in the assembly of the Golgi apparatus, possibly by mediating trafficking to the Golgi membrane. Plays a role in the development of the nervous system, and may be required for neuron projection development. May also play a role during adipose tissue development. Required for maintenance of the ocular lens.

Subunit / interactions. Interacts with STX6. Interacts with STX12. Interacts with RAB6A isoform 1 (GTP-bound) and isoform 2 (GTP-bound). Interacts with RAB6B (GTP-bound).

Subcellular location. Recycling endosome membrane. Cytoplasmic vesicle. Secretory vesicle. Acrosome membrane. Golgi apparatus. cis-Golgi network membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane. trans-Golgi network membrane. Early endosome membrane. Lysosome membrane.

Tissue specificity. Widely expressed. There is apparent differential expression of different transcripts. In fetal brain, lung, liver, and kidney, two transcripts of 2 and 5 kb are identified. These transcripts are also seen in all adult tissues analyzed. A larger transcript (12-14 kb) is expressed in prostate, testis, ovary, and colon in the adult. Expression is very low in adult brain tissue. Expressed in peripheral blood lymphocytes. Isoform 1 and isoform 2 are expressed in brain and retina. Isoform 2 is expressed ubiquitously.

Disease relevance. Cohen syndrome (COH1) [MIM:216550] A rare autosomal recessive disorder characterized by obesity, hypotonia, intellectual deficit, characteristic craniofacial dysmorphism and abnormalities of the hands and feet. Characteristic facial features include high-arched or wave-shaped eyelids, a short philtrum, thick hair and low hairline. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the VPS13 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q7Z7G8-1	1, 1A	yes
Q7Z7G8-2	2, 2A
Q7Z7G8-3	3
Q7Z7G8-4	4
Q7Z7G8-5	5
Q7Z7G8-6	6

RefSeq proteins (3): NP_060360, NP_689777, NP_858047 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009543	VPS13_VAB	Domain
IPR026854	VPS13_N	Domain
IPR039782	VPS13B	Family
IPR056747	VPS13-like_M	Domain

Pfam: PF12624, PF25033, PF25036

UniProt features (69 total): sequence variant 38, splice variant 8, sequence conflict 7, modified residue 5, compositionally biased region 4, region of interest 4, domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q7Z7G8 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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): 414, 999, 1002, 1033, 1815

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (18): acrosome assembly (GO:0001675), lipid transport (GO:0006869), Golgi organization (GO:0007030), nervous system development (GO:0007399), central nervous system development (GO:0007417), muscle organ development (GO:0007517), memory (GO:0007613), vesicle-mediated transport (GO:0016192), dentate gyrus development (GO:0021542), neuron projection development (GO:0031175), slow endocytic recycling (GO:0032458), social behavior (GO:0035176), multicellular organism growth (GO:0035264), maintenance of lens transparency (GO:0036438), head morphogenesis (GO:0060323), adipose tissue development (GO:0060612), Golgi reassembly (GO:0090168), brain development (GO:0007420)

GO Molecular Function (2): phosphatidylinositol-3-phosphate binding (GO:0032266), lipid binding (GO:0008289)

GO Cellular Component (13): Golgi membrane (GO:0000139), acrosomal membrane (GO:0002080), lysosomal membrane (GO:0005765), early endosome membrane (GO:0031901), trans-Golgi network membrane (GO:0032588), cis-Golgi network membrane (GO:0033106), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), recycling endosome membrane (GO:0055038), lysosome (GO:0005764), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
bounding membrane of organelle	3
transport	2
system development	2
head development	2
endosome membrane	2
endomembrane system	2
cytoplasm	2
developmental process involved in reproduction	1
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
lipid localization	1
organelle organization	1
endomembrane system organization	1
nervous system development	1
muscle structure development	1
learning or memory	1
cellular process	1
hippocampus development	1
anatomical structure development	1
neuron development	1
plasma membrane bounded cell projection organization	1
endocytic recycling	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
multicellular organismal process	1
developmental growth	1
tissue homeostasis	1
anatomical structure morphogenesis	1
body morphogenesis	1
connective tissue development	1
Golgi organization	1
cellular component assembly	1
Golgi inheritance	1
central nervous system development	1
phosphatidylinositol phosphate binding	1
binding	1

Protein interactions and networks

STRING

1788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS13B	RAB6A	P20340	785
VPS13B	BBS12	Q6ZW61	584
VPS13B	VPS13A	Q96RL7	532
VPS13B	BBS10	Q8TAM1	517
VPS13B	BBS7	Q8IWZ6	509
VPS13B	JAGN1	Q8N5M9	501
VPS13B	VPS45	Q9NRW7	501
VPS13B	VPS13D	Q5THJ4	492
VPS13B	FBN3	Q75N90	486
VPS13B	LAMTOR2	Q9Y2Q5	476
VPS13B	PGAP2	Q9UHJ9	474
VPS13B	SLC37A4	O43826	474
VPS13B	INPP5E	Q9NRR6	457
VPS13B	AP3B1	O00203	454
VPS13B	NIPAL2	Q9H841	454

IntAct

43 interactions, top by confidence:

A	B	Type	Score
CSNK1E	PER2	psi-mi:“MI:0914”(association)	0.850
CSNK1D	PER2	psi-mi:“MI:0914”(association)	0.810
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
SPEF1	ZBED1	psi-mi:“MI:0914”(association)	0.550
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
FAM177A1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
RAB6B	RAB6A	psi-mi:“MI:0914”(association)	0.530
VPS13B	H1-1	psi-mi:“MI:0915”(physical association)	0.400
VPS13B	HSPA8	psi-mi:“MI:0915”(physical association)	0.400
VPS13B	H3-4	psi-mi:“MI:0915”(physical association)	0.400
Csnk1e		psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	VPS13B	psi-mi:“MI:0914”(association)	0.350
CSNK1D	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SPACA1	ESYT2	psi-mi:“MI:0914”(association)	0.350
IGHM	ESYT2	psi-mi:“MI:0914”(association)	0.350
LYPD4	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
ARL5B	RAD21	psi-mi:“MI:0914”(association)	0.350
SNX20	DIRAS1	psi-mi:“MI:0914”(association)	0.350
SNX21	RBP4	psi-mi:“MI:0914”(association)	0.350
ASIC5	BLVRA	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
UBXN6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
D2HGDH	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
BAG2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
BAG5	ACACB	psi-mi:“MI:0914”(association)	0.350
CIB2	APAF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-MS), VPS13B (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A2AAE1, A2RV80, A4IFQ0, A6QQW8, F1Q8X5, O35382, P48553, P70398, Q08BT5, Q13769, Q2LD37, Q5F361, Q5R903, Q5RAQ5, Q5REX9, Q62824, Q68FX7, Q6DFZ1, Q6IC98, Q6NRC7, Q6P6Y1, Q6SP92, Q6ZWH5, Q7SXV1, Q7TSG1, Q7Z7G8, Q80TY5, Q8BHY8, Q8BKT7, Q8BQZ4, Q8CB44, Q8CIB5, Q8K3W0, Q8N960, Q8WN69, Q8WN70, Q91W96, Q92538

Diamond homologs: A0JNW5, A2RSJ4, Q08D51, Q21480, Q54KX3, Q6NRZ1, Q7Z7G8, Q80TY5, Q96RL7, Q5H8C4, Q709C8, Q8BX70, Q9BGZ0, Q5THJ4, Q86K84, G0S3B8, O42926, P87319, Q54PG5, Q55EI3

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
RAB6A	“down-regulates activity”	VPS13B	binding
RAB6C	“down-regulates activity”	VPS13B	binding
RAB6B	“down-regulates activity”	VPS13B	binding
RAB6A	“up-regulates activity”	VPS13B	binding
RAB6B	“up-regulates activity”	VPS13B	binding
RAB6C	“up-regulates activity”	VPS13B	binding
VPS13B	up-regulates	Neurite_outgrowth

Disease & clinical

Clinical variants and AI predictions

ClinVar

6831 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	635
Likely pathogenic	430
Uncertain significance	2502
Likely benign	2672
Benign	143

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1033869	NM_152564.5(VPS13B):c.10557del (p.Leu3519fs)	Pathogenic
1048631	NM_152564.5(VPS13B):c.3446-23T>G	Pathogenic
1048632	NC_000008.10:g.100246250_100460500del	Pathogenic
1067322	NM_152564.5(VPS13B):c.11216-1G>C	Pathogenic
1068499	NM_152564.5(VPS13B):c.8430del (p.Val2811fs)	Pathogenic
1068584	NM_152564.5(VPS13B):c.8230C>T (p.Gln2744Ter)	Pathogenic
1068728	NC_000008.10:g.(?100654019)(100673739_?)del	Pathogenic
1068729	NC_000008.10:g.(?100654029)(100712170_?)del	Pathogenic
1069053	NM_152564.5(VPS13B):c.11727_11728del (p.Arg3909fs)	Pathogenic
1069136	NM_152564.5(VPS13B):c.6395T>A (p.Leu2132Ter)	Pathogenic
1069655	NM_152564.5(VPS13B):c.10975del (p.Arg3659fs)	Pathogenic
1070547	NM_152564.5(VPS13B):c.2387_2388del (p.Leu796fs)	Pathogenic
1070680	NM_152564.5(VPS13B):c.6315C>A (p.Cys2105Ter)	Pathogenic
1070729	NC_000008.10:g.(?100182257)(100479872_?)del	Pathogenic
1070731	NC_000008.10:g.(?100286406)(100874194_?)del	Pathogenic
1070732	NC_000008.10:g.(?100396426)(100403942_?)del	Pathogenic
1070733	NC_000008.10:g.(?100396426)(100523750_?)del	Pathogenic
1070870	NC_000008.10:g.(?100108530)(100287492_?)del	Pathogenic
1070881	NM_152564.5(VPS13B):c.1527del (p.Arg510fs)	Pathogenic
1070923	NM_152564.5(VPS13B):c.10982del (p.Pro3661fs)	Pathogenic
1071592	NM_152564.5(VPS13B):c.2560C>T (p.Gln854Ter)	Pathogenic
1072023	NM_152564.5(VPS13B):c.9333T>G (p.Tyr3111Ter)	Pathogenic
1073138	NM_152564.5(VPS13B):c.6625dup (p.Ile2209fs)	Pathogenic
1073212	NM_152564.5(VPS13B):c.11252del (p.Asn3751fs)	Pathogenic
1073423	NM_152564.5(VPS13B):c.8461_8462del (p.Leu2821fs)	Pathogenic
1073463	NM_152564.5(VPS13B):c.8437C>T (p.Gln2813Ter)	Pathogenic
1073915	NM_152564.5(VPS13B):c.3068del (p.Thr1023fs)	Pathogenic
1074483	NM_152564.5(VPS13B):c.3492_3493dup (p.Thr1165fs)	Pathogenic
1074670	NC_000008.10:g.(?100568668)(100568891_?)del	Pathogenic
1074671	NC_000008.10:g.(?100654029)(100654736_?)del	Pathogenic

SpliceAI

8380 predictions. Top by Δscore:

Variant	Effect	Δscore
8:99013933:CAGGT:C	donor_loss	1.0000
8:99013934:AGG:A	donor_loss	1.0000
8:99013935:GGTA:G	donor_loss	1.0000
8:99013936:G:GG	donor_gain	1.0000
8:99013937:T:A	donor_loss	1.0000
8:99038420:AAG:A	acceptor_gain	1.0000
8:99038421:A:G	acceptor_gain	1.0000
8:99038421:AGGA:A	acceptor_loss	1.0000
8:99038422:G:GC	acceptor_loss	1.0000
8:99038450:A:G	acceptor_gain	1.0000
8:99038563:ACAGG:A	donor_loss	1.0000
8:99038564:CAGG:C	donor_loss	1.0000
8:99038565:AG:A	donor_loss	1.0000
8:99038566:GG:G	donor_loss	1.0000
8:99038567:G:GC	donor_loss	1.0000
8:99038568:T:A	donor_loss	1.0000
8:99096299:A:AG	acceptor_gain	1.0000
8:99096300:A:AG	acceptor_gain	1.0000
8:99096301:A:AG	acceptor_gain	1.0000
8:99096304:A:AG	acceptor_gain	1.0000
8:99096305:A:G	acceptor_gain	1.0000
8:99096310:AG:A	acceptor_gain	1.0000
8:99096311:GG:G	acceptor_gain	1.0000
8:99100019:C:CG	donor_gain	1.0000
8:99100019:C:G	donor_gain	1.0000
8:99100023:G:GG	donor_gain	1.0000
8:99102948:TATA:T	acceptor_loss	1.0000
8:99102948:TATAG:T	acceptor_gain	1.0000
8:99102950:TAG:T	acceptor_gain	1.0000
8:99102951:A:AC	acceptor_loss	1.0000

AlphaMissense

26363 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:99013817:T:C	L10S	1.000
8:99013841:T:A	I18N	1.000
8:99013879:T:A	W31R	1.000
8:99013879:T:C	W31R	1.000
8:99013881:G:C	W31C	1.000
8:99013881:G:T	W31C	1.000
8:99013898:T:C	L37P	1.000
8:99013907:T:C	L40P	1.000
8:99013913:T:C	L42S	1.000
8:99038453:G:A	G60R	1.000
8:99038453:G:C	G60R	1.000
8:99038454:G:A	G60E	1.000
8:99038469:T:C	L65S	1.000
8:99038475:T:A	I67N	1.000
8:99038486:T:A	W71R	1.000
8:99038486:T:C	W71R	1.000
8:99038488:G:C	W71C	1.000
8:99038488:G:T	W71C	1.000
8:99038537:T:C	C88R	1.000
8:99103013:T:C	L158P	1.000
8:99103016:T:A	I159K	1.000
8:99103019:T:C	L160P	1.000
8:99103021:A:G	K161E	1.000
8:99103022:A:T	K161I	1.000
8:99103023:A:C	K161N	1.000
8:99103023:A:T	K161N	1.000
8:99103043:T:A	V168D	1.000
8:99103046:T:C	L169P	1.000
8:99103066:G:C	A176P	1.000
8:99111152:T:C	L212P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000097 (8:99736136 GAGA>G), RS1000003105 (8:99213799 G>T), RS1000003350 (8:99597013 C>T), RS1000005734 (8:99110325 A>G), RS1000006188 (8:99425776 A>G), RS1000012040 (8:99252878 A>T), RS1000012481 (8:99338869 C>G), RS1000020030 (8:99103423 G>A,C), RS1000021040 (8:99780730 A>C,G), RS1000021356 (8:99767386 T>G), RS1000024087 (8:99872018 T>C), RS1000025690 (8:99161086 A>G), RS1000034862 (8:99624578 C>T), RS1000037366 (8:99254273 T>C,G), RS1000038741 (8:99381294 C>T)

Disease associations

OMIM: gene MIM:607817 | disease phenotypes: MIM:216550, MIM:209850, MIM:192500, MIM:617238, MIM:181500, MIM:160700, MIM:268000, MIM:202700

GenCC curated gene-disease

Disease	Classification	Inheritance
Cohen syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Cohen syndrome	Definitive	AR

Mondo (18): Cohen syndrome (MONDO:0008999), intellectual disability (MONDO:0001071), autism (MONDO:0005260), familial long QT syndrome (MONDO:0019171), microcephaly (MONDO:0001149), neutropenia (MONDO:0001475), canker sore (MONDO:0005318), inherited retinal dystrophy (MONDO:0019118), myopia 25, autosomal dominant (MONDO:0014982), retinal disorder (MONDO:0005283), schizophrenia (MONDO:0005090), congenital nervous system disorder (MONDO:0002320), dental caries (MONDO:0005276), attention deficit-hyperactivity disorder (MONDO:0007743), myopia (MONDO:0001384)

Orphanet (8): Cohen syndrome (Orphanet:193), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Pituitary stalk interruption syndrome (Orphanet:95496), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

99 total (30 of 99 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000164	Abnormality of the dentition
HP:0000189	Narrow palate
HP:0000194	Open mouth
HP:0000212	Gingival overgrowth
HP:0000252	Microcephaly
HP:0000294	Low anterior hairline
HP:0000297	Facial hypotonia
HP:0000322	Short philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000384	Preauricular skin tag
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000444	Convex nasal ridge
HP:0000486	Strabismus
HP:0000492	Abnormal eyelid morphology
HP:0000494	Downslanted palpebral fissures
HP:0000499	Abnormal eyelash morphology
HP:0000505	Visual impairment
HP:0000527	Long eyelashes
HP:0000545	Myopia
HP:0000568	Microphthalmia
HP:0000574	Thick eyebrow
HP:0000580	Pigmentary retinopathy
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002726_66	Glucose homeostasis traits	6.000000e-06
GCST004049_3	Cough in response to angiotensin-converting enzyme inhibitor drugs	2.000000e-06
GCST006110_35	Nose morphology	1.000000e-08
GCST006979_471	Heel bone mineral density	8.000000e-12
GCST008759_4	Intake of total sugars	3.000000e-06
GCST012060_5	Nose morphology	6.000000e-11
GCST90002390_608	Mean corpuscular hemoglobin	6.000000e-09
GCST90002392_589	Mean corpuscular volume	1.000000e-11
GCST90002397_343	Mean spheric corpuscular volume	3.000000e-11
GCST90002403_635	Red blood cell count	1.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006830	insulin metabolic clearance rate measurement
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0009270	heel bone mineral density
EFO:0010158	sugar consumption measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D003731	Dental Caries	C07.793.720.210
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009216	Myopia	C11.744.636
D009503	Neutropenia	C15.378.243.750.184.564; C15.378.553.546.184.564
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D013281	Stomatitis, Aphthous	C07.465.864.750
C536438	Cohen syndrome (supp.)
C565969	Neutropenia, Severe Congenital, Autosomal Dominant 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	5
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	3
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Aflatoxin B1	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	affects methylation	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium bichromate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric chloride	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1

Cellosaurus cell lines

8 cell lines: 5 induced pluripotent stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3UB	ICGi035-A	Induced pluripotent stem cell	Female
CVCL_B3UC	ICGi035-B	Induced pluripotent stem cell	Female
CVCL_C1VE	PNUi003-A	Induced pluripotent stem cell	Female
CVCL_C1VF	PNUi003-B	Induced pluripotent stem cell	Female
CVCL_C1VG	PNUi003-C	Induced pluripotent stem cell	Female
CVCL_E1HQ	HeLa M VPS13B-KO clone 1	Cancer cell line	Female
CVCL_E1HR	HeLa M VPS13B-KO clone 2	Cancer cell line	Female
CVCL_E1HT	HeLa M FAM117A1/VPS13B-DKO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	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
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01907555	Not specified	COMPLETED	Clinical, Molecular and Physiopathological Study of Cohen Syndrome and Cohen-like Syndromes
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	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