VWC2L

Summary

VWC2L (von Willebrand factor C domain containing 2 like, HGNC:37203) is a protein-coding gene on chromosome 2q34-q35, encoding von Willebrand factor C domain-containing protein 2-like (B2RUY7). May play a role in neurogenesis.

Predicted to be involved in negative regulation of BMP signaling pathway. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region and synapse. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in extracellular space.

Source: NCBI Gene 402117 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001080500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37203
Approved symbol	VWC2L
Name	von Willebrand factor C domain containing 2 like
Location	2q34-q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000174453
Ensembl biotype	protein_coding
OMIM	619794
Entrez	402117

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000312504, ENST00000427124, ENST00000477752

RefSeq mRNA: 2 — MANE Select: NM_001080500 NM_001080500, NM_001345929

CCDS: CCDS46509, CCDS86917

Canonical transcript exons

ENST00000312504 — 4 exons

Exon	Start	End
ENSE00001207544	214414114	214414583
ENSE00001672614	214436629	214436758
ENSE00003570589	214575672	214578976
ENSE00003892413	214411054	214411786

Expression profiles

Bgee: expression breadth broad, 36 present calls, max score 71.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1669 / max 71.7681, expressed in 58 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25063	0.0719	36
25062	0.0609	29
25061	0.0342	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	71.10	gold quality
prefrontal cortex	UBERON:0000451	70.97	gold quality
primary visual cortex	UBERON:0002436	68.25	gold quality
hypothalamus	UBERON:0001898	67.04	gold quality
frontal cortex	UBERON:0001870	66.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	65.93	gold quality
anterior cingulate cortex	UBERON:0009835	63.91	gold quality
cerebral cortex	UBERON:0000956	63.55	gold quality
substantia nigra	UBERON:0002038	60.13	gold quality
right frontal lobe	UBERON:0002810	59.42	gold quality
islet of Langerhans	UBERON:0000006	56.55	gold quality
temporal lobe	UBERON:0001871	56.15	gold quality
amygdala	UBERON:0001876	55.97	gold quality
brain	UBERON:0000955	53.99	gold quality
cortical plate	UBERON:0005343	52.07	silver quality
Ammon’s horn	UBERON:0001954	51.17	gold quality
colonic epithelium	UBERON:0000397	49.41	gold quality
bone marrow cell	CL:0002092	48.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	48.87	gold quality
pituitary gland	UBERON:0000007	47.45	gold quality
corpus callosum	UBERON:0002336	45.23	gold quality
adenohypophysis	UBERON:0002196	45.17	gold quality
nucleus accumbens	UBERON:0001882	45.09	gold quality
putamen	UBERON:0001874	44.50	gold quality
ganglionic eminence	UBERON:0004023	44.11	gold quality
calcaneal tendon	UBERON:0003701	43.73	silver quality
caudate nucleus	UBERON:0001873	42.28	gold quality
hindlimb stylopod muscle	UBERON:0004252	42.22	gold quality
pancreas	UBERON:0001264	40.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting VWC2L, 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-8068	99.98	73.85	2376
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-7843-3P	98.31	67.94	803

Literature-anchored findings (GeneRIF, showing 1)

• Vwc2l is a novel secreted protein that promotes matrix mineralization by modulating Osterix expression likely through TGF-beta superfamily growth factor signaling pathway. (PMID:22209847)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	vwc2l	ENSDARG00000069134
mus_musculus	Vwc2l	ENSMUSG00000045648
rattus_norvegicus	Vwc2l	ENSRNOG00000027400

Paralogs (19): CHRDL2 (ENSG00000054938), CHRD (ENSG00000090539), CHRDL1 (ENSG00000101938), TECTA (ENSG00000109927), VWF (ENSG00000110799), MUC5B (ENSG00000117983), KCP (ENSG00000135253), ZAN (ENSG00000146839), CRIM1 (ENSG00000150938), BMPER (ENSG00000164619), OTOGL (ENSG00000165899), VWCE (ENSG00000167992), MUC6 (ENSG00000184956), OTOG (ENSG00000188162), VWC2 (ENSG00000188730), MUC2 (ENSG00000198788), MUC19 (ENSG00000205592), MUC5AC (ENSG00000215182), FCGBP (ENSG00000275395)

Protein

Protein identifiers

von Willebrand factor C domain-containing protein 2-like — B2RUY7 (reviewed: B2RUY7)

Alternative names: Brorin-like

All UniProt accessions (2): B2RUY7, B7ZW27

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in neurogenesis. May play a role in bone differentiation and matrix mineralization.

Subunit / interactions. Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including VWC2L. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing.

Subcellular location. Secreted. Synapse.

Isoforms (2)

UniProt ID	Names	Canonical?
B2RUY7-1	1	yes
B2RUY7-2	2

RefSeq proteins (2): NP_001073969, NP_001332858 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001007	VWF_dom	Domain
IPR042979	VWC2/VWC2L	Family
IPR057856	VWC2L_C	Domain
IPR059152	VWC2L_N	Domain

Pfam: PF23331, PF23333, PF23334

UniProt features (6 total): domain 2, splice variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B2RUY7-F1	77.93	0.37

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_BMP_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_BMP, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_REGULATION_OF_BMP_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_AMPA_GLUTAMATE_RECEPTOR_COMPLEX

GO Biological Process (2): negative regulation of BMP signaling pathway (GO:0030514), positive regulation of neuron differentiation (GO:0045666)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), AMPA glutamate receptor complex (GO:0032281), synapse (GO:0045202), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
binding	1
ionotropic glutamate receptor complex	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VWC2L	CATIP	Q7Z7H3	563
VWC2L	FAM163B	P0C2L3	506
VWC2L	PCYT1B	Q9Y5K3	486
VWC2L	OR6B3	Q8NGW1	480
VWC2L	PRRT2	Q7Z6L0	474
VWC2L	NRN1	Q9NPD7	468
VWC2L	PCMTD2	Q9NV79	462
VWC2L	CLVS2	Q5SYC1	456
VWC2L	TEX2	Q8IWB9	451
VWC2L	ZFYVE19	Q96K21	450
VWC2L	TMEM182	Q6ZP80	438
VWC2L	EXD1	Q8NHP7	434
VWC2L	PUS7L	Q9H0K6	426
VWC2L	NOL10	Q9BSC4	422
VWC2L	SKIDA1	Q1XH10	383

IntAct

92 interactions, top by confidence:

A	B	Type	Score
VWC2L	OTX1	psi-mi:“MI:0915”(physical association)	0.700
	VWC2L	psi-mi:“MI:0915”(physical association)	0.600
VWC2L	SPATA3	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	NR4A3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	VWC2L	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	LCE1A	psi-mi:“MI:0915”(physical association)	0.560
	VWC2L	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	RIPK4	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	LCE5A	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	CEMP1	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	C22orf39	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	CXCL5	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	CRCT1	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	TYRO3	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	C17orf50	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	ZNF20	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	TRIM42	psi-mi:“MI:0915”(physical association)	0.560
SPATA3	VWC2L	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	FBXO34	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (40): OTX1 (Two-hybrid), FHL3 (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), VWC2L (Two-hybrid), FBXO34 (Two-hybrid), DEFB112 (Two-hybrid)

ESM2 similar proteins: A0A218QX39, A0A6B9KZ59, A0A6B9KZ79, A0A6B9KZ89, A0A6B9L3M7, A0A7M6UNN1, A7VN13, A7VN14, A7VN15, A7VN16, B0JFB8, B0UZC8, B2RUY7, B7PCV3, B8XH22, C5J895, L0GB04, L0GCJ1, L0GCW8, L7X735, M1E1F0, O77416, O77417, O77418, P09036, P09655, P09656, P0CJ12, P0DM55, P0DQC5, P0DQC6, P0DQC9, P0DQD0, P0DQE2, P0DQG2, P0DQG4, P0DQG7, P0DQG8, P0DQG9, P0DRJ1

Diamond homologs: B0UZC8, B2RUY7, P05997, P28481, Q2TAL6, Q3U962, Q505H4, Q7T3Q2, Q8AWW5, Q8C8N3, Q95K75, Q9IBG7, Q6WN34, A0MSJ1, B8V7R6, C0HM85, C0HM86, C0HM87, C0HM88, C0HM90, C0HM92, C0HM93, C0HM95, O42350, O46392, O88207, O93484, O94769, P02452, P02453, P02454, P02457, P02458, P02459, P02460, P02461, P02465, P02466, P02467, P05539

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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
Keratinization	7	27.9×	4e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1863 predictions. Top by Δscore:

Variant	Effect	Δscore
2:214575670:A:AG	acceptor_gain	1.0000
2:214575670:A:C	acceptor_loss	1.0000
2:214575671:G:GG	acceptor_gain	1.0000
2:214575671:GGTCC:G	acceptor_gain	1.0000
2:214411207:C:G	donor_gain	0.9900
2:214414575:GAATT:G	donor_gain	0.9900
2:214575671:GGT:G	acceptor_gain	0.9900
2:214575671:GGTC:G	acceptor_gain	0.9900
2:214411392:CTGT:C	donor_gain	0.9800
2:214411394:GT:G	donor_gain	0.9800
2:214411450:GATC:G	donor_gain	0.9800
2:214436627:A:AG	acceptor_gain	0.9800
2:214436628:G:GG	acceptor_gain	0.9800
2:214510213:GAT:G	donor_gain	0.9800
2:214575668:TCAGG:T	acceptor_gain	0.9800
2:214575669:CAGGT:C	acceptor_gain	0.9800
2:214575670:AG:A	acceptor_gain	0.9800
2:214575671:GG:G	acceptor_gain	0.9800
2:214414524:G:GT	donor_gain	0.9700
2:214414579:TTAAG:T	donor_loss	0.9700
2:214414580:TAAG:T	donor_loss	0.9700
2:214414581:AAGG:A	donor_loss	0.9700
2:214414582:AG:A	donor_loss	0.9700
2:214414583:GGTA:G	donor_loss	0.9700
2:214414584:GT:G	donor_loss	0.9700
2:214414585:T:A	donor_loss	0.9700
2:214436628:GCC:G	acceptor_gain	0.9700
2:214436754:AAATG:A	donor_loss	0.9700
2:214436756:ATGGT:A	donor_loss	0.9700
2:214436757:TGGT:T	donor_loss	0.9700

AlphaMissense

1488 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:214414350:T:A	C53S	1.000
2:214414350:T:C	C53R	1.000
2:214414351:G:C	C53S	1.000
2:214414393:T:G	F67C	1.000
2:214414425:T:C	C78R	1.000
2:214414427:T:G	C78W	1.000
2:214414482:T:A	C97S	1.000
2:214414482:T:C	C97R	1.000
2:214414483:G:C	C97S	1.000
2:214414484:T:G	C97W	1.000
2:214414518:T:A	C109S	1.000
2:214414518:T:C	C109R	1.000
2:214414519:G:C	C109S	1.000
2:214414539:T:A	C116S	1.000
2:214414540:G:A	C116Y	1.000
2:214414540:G:C	C116S	1.000
2:214414541:T:G	C116W	1.000
2:214414578:T:C	F129L	1.000
2:214414579:T:C	F129S	1.000
2:214414579:T:G	F129C	1.000
2:214414580:T:A	F129L	1.000
2:214414580:T:G	F129L	1.000
2:214436647:T:A	C137S	1.000
2:214436647:T:C	C137R	1.000
2:214436648:G:A	C137Y	1.000
2:214436648:G:C	C137S	1.000
2:214436649:T:G	C137W	1.000
2:214436651:G:C	R138P	1.000
2:214436653:T:A	C139S	1.000
2:214436653:T:C	C139R	1.000

dbSNP variants (sampled 300 via entrez): RS1000023534 (2:214543198 C>G), RS1000024065 (2:214540618 C>A,T), RS1000029180 (2:214470461 G>C,T), RS1000039448 (2:214419642 C>G), RS1000047112 (2:214572753 T>A), RS1000056250 (2:214566711 C>T), RS1000059801 (2:214543761 AG>A), RS1000109898 (2:214566563 C>A,T), RS1000139174 (2:214576562 C>A,G), RS1000179885 (2:214412378 A>G), RS1000190409 (2:214576822 T>C), RS1000236084 (2:214415786 G>A), RS1000241552 (2:214538342 G>T), RS1000246295 (2:214481367 A>C), RS1000262404 (2:214521058 C>A,T)

Disease associations

OMIM: gene MIM:619794 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001925_4	PR interval	5.000000e-06
GCST005232_9	Neuroticism	6.000000e-09
GCST009304_16	Degraded stimulus continuous performance test score	6.000000e-06
GCST009524_166	Household income (MTAG)	9.000000e-12
GCST009524_302	Household income (MTAG)	1.000000e-09
GCST009600_84	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	7.000000e-09
GCST010599_1	Dietary fat liking	8.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0007660	neuroticism measurement
EFO:0007636	attention function measurement
EFO:0009695	household income
EFO:0010816	dietary fat liking measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
perfluorooctanoic acid	decreases expression	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Air Pollutants	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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